Archive for October, 2019

During the week, online newspaper, TheCable published an expose on the rot and other shady deals that take place at police stations.

Although they zeroed in on a particular police station in Lagos, however, what they exposed is what is happing at the various other police stations dotted across the length and breadth of this country.

In the story, captioned: UNDERCOVER INVESTIGATION (I): Bribery, bail for sale Lagos police station where innocent civilians are held and criminals are recycled, TheCable wrote in their intro to the piece: Investigative journalist FISAYO SOYOMBO spent two weeks in detention five days in a Police cell and eight as an inmate in Ikoyi Prison to track corruption in Nigerias criminal justice system, beginning from the moment of arrest by the Police to the point of release from prison.

To experience the workings of the system in its raw state, Soyombo adopting the pseudonym Ojo Olajumoke feigned an offence for which he was arrested and detained in police custody; arraigned in court and eventually remanded in Prisonhe uncovers how the Police pervert the course of justice in their quest for ill-gotten money.

TheCable then goes on to give a vivid account of what transpires at the Pedro Police Station and even Ikoyi Prison through the first-hand experience of their undercover reporter.

In one instance, Ojo Olajumoke wrote: The complainant was already registering the case with a policewoman by the time we returned, and soon after they were haggling over the fees. Chigozie Odo, the policewoman, had rejected his offer of N500. After some five minutes of talking, he handed her a N1, 000 note.

Odo stripped me of my shirt, singlet, belt, wristwatch, shoes and cash. Look at his hair; na you gangan be Ruggedy Baba, she said as she unlocked the cell and bundled me in.

This report was only published during the week, but sadly, I can point out that this has been the pattern for decades; because I have also personally experienced it.

In my own case, it was not an attempt to expose the rot through fine investigative reporting, but rather I was a forced participant because a then military governor wanted to deal with my then medium, The Guardian.

I have actually written the story before in a piece I titled How Champions League landed me in Kirikiri Prison, which I wrote to commemorate the 25th year that I and three other colleagues, Bayo Oguntimehin, Taiwo Akerele and Ben Akparanta (now late) were hounded into detention for about 16 days, first at Alausa Police Station and then Motor Traffic Division (MTD), both in Ikeja, Lagos, before ending up in Kirikiri Medium Prisons, just because the then governor Col, Raji Rasaki (rtd) had some bones to pick with the flagship over The Guardians critical position on some of his actions as governor of Lagos.

Our ordeal began on May 29, 1991 when the then governor made his move leading to the closure of The Guardian by the state government.

At both Alausa and MTD, we witnessed first-hand how the police who claim to be our friends interact with those who come to the station to either lodge complaints or are brought in for allegedly committing and offence.

They (police officers) were mostly unfriendly towards such people and more often than not were ready to either bend the law or dish out favours following the receipt of some form of gratification.

For instance, on the first night of our detention after our management had spoken to the officers on duty, we were not immediately shoved into the detention cells with other suspects.

Instead, we were kept outside until about midnight before we were told we had to be put into the cell because it was against the law to allow suspects spend a whole night outside the holding bay.

But of course, before sending us into the cell, they (police) had spoken to the president to ensure that we (journalists) were not given the traditional welcoming which is often a severe beating.

And just like Ojo Olajumoke wrote, I still recall having to remove my belt, watch and other valuables on me and when I jokingly asked what would happen should my trousers not stay up without a belt, I was told if that be the case, then I would have to hold my sokoto because I could not enter the cell with a belt so that I dont use it to commit suicide or as a weapon!

Those in the holding cells were a sorry sight to behold with many of them complaining that they had been thrown in on trumped up charges and would only regain their freedoms as soon as they settled.

Many of them were brought in for wandering, which was then an offence that the police exploited very well in apprehending people.

Although it is often said lightening does not strike twice, however, I have been an exception; and six years after my Kirikiri trip, I was again a forced guest of the police, after I and my two other co-tenants were arrested for armed robbery and gun running.

Incidentally, I had just arrived in the country from Egypt, where I had gone to cover the FIFA U17 World Cup when this fresh incident occurred.

This time we were lodged at the Adeniji Adele Police Station, while we battled to extradite ourselves from the case, which if not properly handled could see me face the death penalty.

Sadly, during the course of our investigation, we were told by our fellow detainees, that we had actually been setup by one of our fellow tenants, who was the only one not with us in detention.

We were told that he (the tenant) had come to the police that he could make money for them by writing a petition that he knew of some armed robbery suspects who once caught would be ready to cough up money in order to free themselves and it was this money that they (the tenant and police) would share.

Unfortunately in the end, the police doubled crossed him on the grounds that the money they made was not as much as he had claimed they would make.

Both stories were subsequently written, but here more than two decades after, we are reading the same story all over a clear indication that absolutely nothing had changed!

And this sadly is one of the biggest problems we face in this country failure to tackle issues head on in order to improve as a nation.

Instead we will all complain about poor governance and yet still vote for the same people that are the hindrance to the nation having decent governance.

At the end of the day, the path to a decent society lies with us as a people, who must then decide once and for all that enough is enough and we are now ready for real change and not just mouth change.

Unless this happens, I can bet that two decades down the line another Ojo Olajumoke will write another expose on virtually the same issue.

Like Loading...

Related

Advertisements

See the rest here:
When the hair falls off - New Telegraph Newspaper

Although Lo Vauclare is just 3 years old, his kisses are known around the world.

A Franco-American living in Paris with his parents and little sister, Lo is the boy behind Bisous for Leo, a nonprofit organization named with the French word for kisses.

He loves swimming in the pool, listening to music and laughing. His big eyes light up behind a pair of large, round spectacles every he time he smiles which is often.

But he has trouble eating. He can no longer hold himself upright without support.

When Lo was born, he developed like any other child crawling, cruising and then finally taking his first steps. But his mother, Deborah Vauclare, said he never got past that. He would fall every few paces.

At about 15 months, Los parents took him to the doctor, who assured them that some children take a few more months to learn how to walk.

But when the toddler continued to falter, his parents worries grew. Extensive testing and therapy followed. Then they pursued genetic testing.

The results showed their son had Infantile Neuroaxonal Dystrophy or INAD, an extremely rare neurodegenerative disease that robs children of their fledgling abilities. It can weaken their muscles, taking away their ability to walk, hold up their own heads or control their eye movements, according to the INADcure Foundation.

Vauclare called the disease a mixture of Alzheimers and Parkinsons that impacts children.

Antoine, Deborah and Lo Vauclare are the family behind Bisous for Lo, a nonprofit organization that raises funds for research on INAD, a neurodegenerative disease that affects Lo.

(Courtesy of Deborah Vauclare)

The Vauclares had just received the devastating news last June when their close family friend, Emily Rogath Steckler, visited Paris with her daughter, Chloe.

The Stecklers had scarcely arrived at the Vauclares apartment when the two little friends perched together on the windowsill.

Chloe planted a kiss on Lo.

And from there, the nonprofit organization was born.

I literally couldnt get it out of my head, said Steckler, who co-founded Bisous for Lo with Vauclare. I just knew everybody needed to be embraced and to have the kiss.

Bisous for Lo has since raised more than $200,000 for gene therapy research at Washington University in St. Louis, Vauclare said.

The organization funnels funds through the INADcure Foundation to researchers addressing INAD and similar diseases. The organizations Facebook page collects posts tagged with kisses and stories from other children with INAD worldwide.

Recently, the group collaborated nationwide with Martin Lawrence Galleries, which is owned by Stecklers parents, David and Leslee Rogath. A portion of sales from reprints of artist Robert Deybers piece, Seal with a Kiss, will benefit Bisous for Lo.

Deyber is known for his artistic plays on literal phrases. His works include Love Sick, depicting a polar bear spewing hearts out of its mouth, and The Right to Arm Bears showing a polar bear standing beside a cannon.

Seal with a Kiss, a painting of a proud pinniped with a big red kiss on its cheek preening atop a rock, was the perfect fit for Bisous for Lo.

I think it may have popped up in a conversation or something. ... It will hit me, and Ill be like, Oh my God, seal! Deyber said with a laugh. Its gotten to be where its taken over my life at this point.

Funds from the lithograph sales of artist Robert Deybers piece Seal with a Kiss will be donated to the nonprofti organization Bisous for Lo.

(Courtesy of the Martin Lawrence Galleries)

Funds from the lithograph sales will support research on gene therapy and treatment taking place in the United States and Europe, Vauclare said.

The challenge, Vauclare added, is to convince researchers studying Alzheimers and Parkinsons to pay attention to INAD a disease that Vauclare said impacts only about 150 children worldwide.

Vauclare recently resigned from her job at an architectural firm so she can spend more time working on the nonprofit and supporting her son.

The second my kids go to bed at night, Im on the computer basically until my eyes shut, every single night, she said.

Lo, now 3, is participating in a clinical trial that will last until June. Despite trips between the United States and Paris for treatments, Vauclare said her son remains cheerful.

I definitely think as the disease progresses, we see a little bit less, she said. But even though we see less of it, its very pleasant in the morning when he wakes up and gives you a big smile. It takes him longer to connect with you.

With every social media post and painting sold, the Vauclare family hopes to kiss the disease goodbye.

Donations can be made at BisousForLeo.org and lithographs may be purchased at martinlawrence.com/pages/every-kiss-counts.

Support our coverage by becoming a digital subscriber.

Go here to read the rest:
Sealed with a kiss: how one little boy in Paris is stealing hearts in Costa Mesa - Los Angeles Times

The National Institutes of Health (NIH) announced a partnership with the Bill and Melinda Gates Foundation on Wednesday to fund the development of targeted cures for HIV and sickle cell disease with a view to helping people in developing countries using gene therapy. With most of the populations affected by each disease residing in sub-Saharan Africa, treatments are being sought with regional conditions in mind.

The NIH and the Gates Foundation are investing $100 million in the initiative to develop low-cost gene therapies. The announcement follows President Donald Trump's pledge in his 2019 State of the Union address that the United States would eradicate HIV within the next decade. The Trump administration has also tried to draw more attention to sickle cell disease (SCD) in the past few years, according to a press release from NIH.

Sickle cell disease is a blood disorder that can cause anything from mild pain to heart failure. Human immunodeficiency virus (HIV) is a communicable disease that, if left untreated, wipes out the immune system. People with SCD inherit the disease from their parents, whereas HIV is acquired through blood contamination with certain bodily fluids of an infected person. While the mechanisms of transmission are different, both diseases are carried in the genome of infected individuals. Globally, both diseases also disproportionately impact individuals in lower-income communitiesand scientists believe that both could be combatted with gene-based treatments.

The past few years have seen unprecedented strides toward cures for these two diseases using gene therapy, which the NIH defines as experimental technique wherein doctors insert genes into a patient's cells so their body can more effectively resist a disease. It can include inserting a healthy variant of a gene to replace the unhealthy copy that causes a disease, or placing an entirely new gene in the body to fight the disease.

"Dramatic advances in genetics over the last decade have made effective gene-based treatments a reality... Yet these breakthroughs are largely inaccessible to most of the world by virtue of the complexity and cost of treatment requirements, which currently limit their administration to hospitals in wealthy countries," the press release states. The new initiative will focus on developing treatments that can be delivered in "low-resource settings."

Speaking on the initiative's viability, Dr. Ronald Mitsuyasu, a professor of medicine in hematology-oncology at the University of California, Los Angeles with more than 25 years of experience in HIV clinical trials research, told Newsweek that this sort of solution has been attempted in the past, but gene therapy hasn't yet proved successful in treating HIV.

"There have been several attempts to use gene therapy for HIV by either incorporating genes that suppress HIV genes, producing decoys for various viruses required processes needed for viral replication, or substituting inactive genes for functional genes of HIV," he said.

But those living in developing countries have not had as many chances to benefit from these solutions as those living in places like the U.S., according to the press release.

"SCD and HIV are major burdens on health in low-resource communities around the world," the press release read. "Approximately 95% of the 38 million people living with HIV globally are in the developing world, with 67% in sub-Saharan Africa, half of whom are living untreated. Fifteen million babies will be born with SCD globally over the next 30 years, with about 75% of those births occurring in sub-Saharan Africa."

Further, the prediction indicates that three-quarters of those infants will be born into low-income countries and communities. Between 50 and 90 percent of babies born with the disease in sub-Saharan African countries will die before the age of five, according to the release.

So, the NIH and the Gates Foundation's initiative aims to identify potential cures for both diseases as well as partner with groups in Africa to identify candidates on whom these new cures can be tested.

We are losing too much of Africa's future to sickle cell disease and HIV. Beating these diseases will take new thinking and long-term commitment. I'm very pleased to see the innovative collaboration announced today, which has a chance to help tackle two of Africa's greatest public health challenges." Matshidiso Rebecca Moeti, M.B.B.S., the World Health Organization's regional director for Africa said of the initiative.

Mitsuyasu said he agreed that continued investigation into gene-based cures would eventually yield worthwhile results. "I personally believe that it should be possible to ultimately develop a gene therapy approach to overcome ... HIV," Mitsuyasu said. "Continued scientific developments in the field of gene therapy will eventually allow for the conquest of most genetic and viral gene integrated diseases."

Go here to see the original:
Gates Foundation, NIH Bet on Gene Therapy To Bring Cheap HIV and Sickle Cell Cures to Sub-Saharan Africa - Newsweek

NEW YORK and BASEL, Switzerland, Oct. 23, 2019 (GLOBE NEWSWIRE) -- Axovant Gene Therapies Ltd. (AXGT), a clinical-stage company developing innovative gene therapies, today announced preliminary data from an expanded access study administering investigational AXO-AAV-GM2 gene therapy in two patients with infantile Tay-Sachs disease (TSD) at the 27th Annual Congress of the European Society of Gene and Cell Therapy. Infantile TSD, a rapidly progressive and fatal pediatric neurodegenerative genetic disorder, has a median life expectancy of approximately 3-4 years. This data indicates the potential to modify the rate of disease progression in children with infantile TSD.

Todays exciting clinical results from the AXO-AAV-GM2 program are the first reported evidence for potential disease modification in Tay-Sachs disease, and suggest an opportunity for gene replacement therapy to improve outcomes for children with this devastating condition, said Dr. Gavin Corcoran, chief R&D officer at Axovant. Myelination is an important component of healthy brain development in infants and is often abnormal in children with Tay-Sachs disease. We were encouraged to see MRI evidence of preserved brain architecture and improved myelination in the early symptomatic child treated at 10 months of age, coupled with stability of neuromuscular function as measured on the CHOP INTEND scale. We look forward to Dr. Terry Flottes presentation of this data at the ESGCT conference where he will describe these two clinical cases in detail.

Key findings from this first-in-human study in patients treated with AXO-AAV-GM2, an investigational gene therapy designed to restore -Hexosaminidase A enzyme activity in the central nervous system, include:

*CHOP INTEND is a 16-item scale of motor function that has been validated in infants with neuromuscular disorders. Items of motor function are graded from 0 to 4 for each item, where zero equals no response, and 4 equals a complete response. Change from baseline in total score of 4 points or a total score sustained > 40 points has been associated with a clinically meaningful benefit.

Dr. Terence Flotte, Professor of Pediatrics and Dean at the School of Medicine, University of Massachusetts Medical School, said, Bilateral intrathalamic and intrathecal delivery of rAAV gene therapy may surmount the obstacle of providing widespread distribution of therapeutic enzyme throughout the brain and CNS. This innovative delivery could overcome one of the primary challenges for developing treatments for Tay-Sachs, Sandhoff and many other severe pediatric genetic disorders, providing much needed hope for these families.

Dr. Flotte will present this data on AXO-AAV-GM2 in the First-in-Human gene therapy session on October 23, 2019 at 5:30 PM Central European Time (CET).

About AXO-AAV-GM2

AXO-AAV-GM2 is an investigational gene therapy for Tay-Sachs and Sandhoff disease, which rare and fatal pediatric neurodegenerative genetic disorders within the GM2 gangliosidosis family, caused by defects in theHEXA(leading to Tay-Sachs disease) orHEXB(leading to Sandhoff disease) genes that encode the two subunits of the -hexosaminidase A (HexA) enzyme. Both forms of GM2 gangliosidosis are caused by overwhelming storage of GM2 ganglioside within neurons throughout the central nervous system), which is normally degraded in the lysosome by the isozyme HexA. These genetic defects lead to progressive neurodegeneration and shortened life expectancy. AXO-AAV-GM2 aims to restore HexA levels by introducing a functional copy of theHEXAandHEXBgenes via delivery of two co-administered AAVrh8 vectors.

In 2018, Axovant licensed exclusive worldwide rights from the University of Massachusetts Medical School for the development and commercialization of gene therapy programs for GM1 gangliosidosis and GM2 gangliosidosis, including Tay-Sachs and Sandhoff diseases.

About Axovant Gene Therapies

Axovant Gene Therapies, part of the Roivant family of companies, is a clinical-stage gene therapy company focused on developing a pipeline of innovative product candidates for debilitating neurological and neuromuscular diseases. Our current pipeline of gene therapy candidates targets GM1 gangliosidosis, GM2 gangliosidosis (including Tay-Sachs disease and Sandhoff disease), and Parkinsons disease.

Story continues

Axovant is focused on accelerating product candidates into and through clinical trials with a team of experts in gene therapy development and through external partnerships with leading gene therapy organizations. For more information, visitwww.axovant.com.

About Roivant

Roivantaims to improve health by rapidly delivering innovative medicines and technologies to patients.Roivantdoes this by buildingVants nimble, entrepreneurial biotech and healthcare companies with a unique approach to sourcing talent, aligning incentives, and deploying technology to drive greater efficiency in R&D and commercialization. Roivant today is comprised of a central technology-enabled platform and 20 Vants with over 45 investigational medicines in clinical and preclinical development and multiple healthcare technologies. For more information, please visitwww.roivant.com.

About the University of Massachusetts Medical School

The mission of the University of Massachusetts Medical School is to advance the health and well-being of the people of the commonwealth and the world through pioneering education, research, public service and health care delivery.

Research into potential therapies for lysosomal storage diseases such as Tay-Sachs, Sandhoff disease and GM1 gangliosidosis at UMass Medical School and Auburn University has led to significant advances in the field. Miguel Sena-Esteves, PhD, associate professor of neurology at UMass Medical School; Heather Gray-Edwards, PhD, DVM, formerly of Auburn and currently assistant professor of radiology at UMass Medical School; and Douglas Martin, PhD, professor of anatomy, physiology and pharmacology in the College of Veterinary Medicine and the Scott-Ritchey Research Center at Auburn University, have worked collaboratively for more than a decade on animal models and therapeutic approaches for these and similar disorders. For more information, visit http://www.umassmed.edu.

Forward Looking Statements and Information

This press release contains forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995 and other federal securities laws. The use of words such as may, might, will, would, should, expect, believe, estimate, and other similar expressions are intended to identify forward-looking statements. For example, all statements Axovant makes regarding the initiation, timing, progress, and reporting of results of its preclinical programs, clinical trials, and research and development programs; cash to be used in operating activities; its ability to advance its gene therapy product candidates into and successfully initiate, enroll, and complete clinical trials; the potential clinical utility of its product candidates; its ability to continue to develop its gene therapy platforms; its ability to develop and manufacture its products and successfully transition manufacturing processes; its ability to perform under existing collaborations with, among others, Oxford Biomedica, and theUniversity of Massachusetts Medical School, and to add new programs to its pipeline; its ability to enter into new partnerships or collaborations; its ability to retain and successfully integrate its leadership and personnel; and the timing or likelihood of its regulatory filings and approvals are forward-looking. All forward-looking statements are based on estimates and assumptions by Axovants management that, although Axovant believes to be reasonable, are inherently uncertain. All forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those that Axovant expected.Such risks and uncertainties include, among others, the initiation and conduct of preclinical studies and clinical trials; the availability of data from clinical trials; the expectations for regulatory submissions and approvals; the continued development of its small molecule and gene therapy product candidates and platforms; Axovants scientific approach and general development progress; and the availability or commercial potential of Axovants product candidates. These statements are also subject to a number of material risks and uncertainties that are described in Axovants most recent Quarterly Report on Form 10-Q filed with theSecurities and Exchange CommissiononAugust 9, 2019, as updated by its subsequent filings with theSecurities and Exchange Commission. Any forward-looking statement speaks only as of the date on which it was made.Axovant undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise.

Contacts:

Media and Investors

Parag MeswaniAxovant Gene Therapies (212) 547-2523investors@axovant.commedia@axovant.com

See original here:
Axovant Presents First Evidence of Clinical Stabilization in Tay-Sachs Disease at the European Society of Gene and Cell Therapy 27th Annual Congress -...

Here we go again.

This week, investors may have seen that a new gene editing technique will soon be available to scientists attempting to engineer DNA for human health applications. Dubbed "prime editing," some have called it a game-changer due to its inherent advantages over more commonly used CRISPR techniques. It has the potential to correct up to 89% of disease-causing mutations and is engineered to make more precise edits than other gene editing techniques. And it all belongs to a new start-up: Prime Medicine.

But despite all of the media hype, prime editing has one enormous problem that may make it impossible to commercialize: The molecular components are way too big to be delivered into cells using current methods. It's as if an automaker designed a car with an amazing interior, but forgot to add wheels.

The "big" obstacle facing prime editing doesn't necessarily mean CRISPR Therapeutics (NASDAQ:CRSP), Editas Medicine (NASDAQ:EDIT), and Intellia Therapeutics (NASDAQ:NTLA) will have smooth sailing ahead, but it does highlight an important facet of gene editing technologies that investors can't overlook: delivery.

Cutting both strands of DNA is bad. Image source: Getty Images.

Healthcare investors are probably familiar with the basics of how CRISPR gene editing works by now, but a little refresher can't hurt.

The payload comprises a guide RNA and a cutting enzyme such as Cas9. The guide RNA helps the payload locate the target sequence of DNA that will be edited. Once located, the payload binds to the target sequence of DNA, and the cutting enzyme makes a double-stranded break (meaning it cuts through both strands of DNA) to remove or insert DNA.

But there are problems. The guide RNA and cutting enzyme aren't always 100% accurate, and can sometimes edit the genome relatively far from the target site. That can introduce changes to the genome, which can be harmless -- or potentially harmful.

An even larger problem is that traditional CRISPR gene editing techniques make double-stranded DNA breaks that require one of two natural DNA repair mechanisms to patch up. Unfortunately, there can be significant consequences to this, such as allowing a dormant cancer cell to proliferate and reduced editing efficiency. This problem isn't alleviated by using different cutting enzymes, such as switching from Cas9 to Cas12.

While CRISPR Therapeutics, Editas Medicine, and Intellia Therapeutics have gone all-in on CRISPR-Cas systems, many scientists aren't confident that the technique will deliver on its promise in a clinical setting. But the learning experiences in the lab have spurred a search for new gene editing techniques that don't make as many off-target edits and don't make double-stranded breaks. Prime editing is the latest tool.

Cutting one strand of DNA is better. Image source: Getty Images.

Prime editing makes some notable modifications to the traditional CRISPR-Cas setup. The cutting enzyme, Cas9, has been modified to only cut one strand of DNA. The guide RNA deployed also contains the instructions for the desired edit. And a second enzyme, called reverse transcriptase, has been added to the payload to write the desired edits into the exposed strand of target DNA.

The changes allow prime editing to change any DNA base -- A, T, C, or G -- into any other. Prime editing has also been used to insert up to 44 base letters and delete up to 80 base letters from target DNA in limited studies. It may not seem like much considering the human genome contains over 3 billion base pairs, but the characteristics described above could allow the new technique to correct up to 89% of disease-causing mutations in humans.

The versatility is pretty amazing, but the problem is that prime editing payloads -- comprising two enzymes and a longer guide RNA -- are too large to be delivered with today's delivery vehicles, such as adeno-associated viruses (AAV); after all, enzymes are big. The field of gene therapy only recently overcame the hurdle of delivery, and gene editing is still trying to figure it out.

CRISPR Therapeutics has (perhaps wisely) kicked that can down the road by focusing initial efforts on ex vivo editing, or editing cells in a controlled environment outside of the human body, where delivery is somewhat less complicated. Editas Medicine has taken up the mantle of being the first to try in vivo editing, or editing cells directly in the human body. It's using AAV delivery vehicles initially.

Meanwhile, Intellia Therapeutics has fallen out of favor with investors because its slow-and-steady approach won't let it enter clinical trials until 2020 or 2021. But investors may be missing the point. Rather than plowing ahead with AAV delivery, the company is working to develop new and novel delivery systems based on lipid nanoparticle (LNP) tech licensed from Novartis. It could end up being the main differentiator in the CRISPR gene editing space, and the move is entirely aimed at solving the tricky problem of delivery.

There's also Precision BioSciences (NASDAQ:DTIL), which has a proprietary gene editing system called ARCUS. The tech is completely shielded from CRISPR patent disputes, doesn't make double-stranded DNA cuts, is ahead of CRISPR Therapeutics in an important clinical area, and can diversify its revenue by forging into agriculture or industrial biotech. It relies on AAV delivery vehicles.

Simply put, at a time when gene editing techniques are attempting to figure out the best solution to overcome delivery obstacles, prime editing went all-in on optimizing other characteristics of the tool, while betting the delivery problem will solve itself. That's a risky bet.

Image source: Getty Images.

Luckily for scientists and investors, the swift rise of CRISPR gene editing in research settings has led to the development of robust testing tools. That should shorten the learning curve for researchers wanting to know whether or not prime editing is going to live up to the hype -- or overcome its big delivery problem.

Nonetheless, the media hype highlights that individual investors need to be more selective in their approach to gene editing stocks. Tools that make double-stranded breaks (read: CRISPR) are likely to have a high rate of failure, but ex vivo applications in engineering immune cells could yield success. That would bode well for CRISPR Therapeutics and Precision BioSciences.

The delivery problem will make in vivo editing much more difficult, which could be a problem for Editas Medicine's lead drug candidates and future areas of focus of CRISPR Therapeutics. Intellia Therapeutics is hopeful its LNP approach could solve the problem, but it's too soon to know.

That said, there's one gene editing technique that could strike a balance between traditional CRISPR-Cas systems and prime editing: base editing. It was developed by the same lab that pioneered prime editing and belongs to a start-up called Beam Therapeutics, and Editas Medicine may already have one foot in the doorto licensing the tech. Then again, the gene editing space is very young and rapidly evolving, so investors cannot dismiss the inherent risks of owning gene editing stocks.

More:
There's Yet Another Gene Editing Technique, but It Has 1 Glaring Problem - Motley Fool

MEDIA CONTACT

Available for logged-in reporters only

Newswise October 25, 2019 Major burns lead to changes in the gastrointestinal tract bacteria, and these alterations of the gut microbiome are influenced by resuscitation with intravenous (IV) fluids, according to animal studies reported inSHOCK: Injury, Inflammation, and Sepsis: Laboratory and Clinical Approaches,Official Journal of theShockSociety. The journal is published in the Lippincott portfolio byWolters Kluwer.

Potentially disease-causing gut bacteria are increased after a major burn, while large volumes of IV fluids promote recovery of beneficial bacteria, suggest the experiments by David Burmeister,PhD, of the US Army Institute of Surgical Research and colleagues. They write, "This study is the first to show that the gut microbiome is altered following a large burn injury in pigs and that the gut microbiome may be influenced by the resuscitation strategy used."

Gut Microbiome Changes May Affect Outcomes After Major Burns

Burnsdon'tjust cause skin damage they result in physiological stress and inflammation that may lead to infections and other serious complications. While a growing body of research has shown that the gut microbiome has important effectsforhealth and disease, little is known about how burns may alter the microbiome.

The researchers examined changes in the gut bacteria after burns and how those alterations are affected by fluid resuscitation. Major burns, covering 40 percent of body surface area, were induced in anesthetized swine. Because their skin and gastrointestinal tract are similar to those of humans, pigs are an important model for studying burns and their treatment.

The animals then received low- or high-volume fluid resuscitationor no IV fluids. Effects on gut microbiome diversity the proportions of different types of bacteria were analyzed by isolating and analyzing bacterial DNA.

The results showed significant changes in the gut microbiome after burns, with disruption of the normal balance between different groups of bacteria. Findings included a "hyperacute spike" in one major group called Proteobacteria, which includes many potentially pathogenic (disease-causing) organisms.

In contrast, high volumes of resuscitation fluids seemed to promote recovery of potentially beneficial microbes, such asBacteroidesbacteria. SinceBacteroidesplays a role in converting sugar into energy, this shift might help in coping with the increased metabolic demands on the body after burns. Fluid resuscitation also prevented increases in certain opportunistic bacteria, which might protect against the risk of sepsis and other serious infections.

Resuscitation fluids also seemed to affect some functional proteins in the gut for example, heat shock proteins that promote resistance to stress-induced cell damage. That provides a clue to understanding how fluid resuscitation helps the body recover from inflammation and other metabolic changes after burns.

Despite increasing evidence on the role of the gut microbiome, there has been little information on how bacterial diversity in the gut is affected by burns and their treatment. While early, aggressive fluid resuscitation is a key part treatment for burns,debatecontinues over the resuscitation strategies used.

Dr. Burmeister and colleagues call for further studies to clarify shifts in microbiome diversity after burns, and how these changes affect the outcomes of burns and responses to fluid resuscitation. Future research might lead to new treatments targeting the microbiome for example, using fecal transplant or antibiotics to promote recovery after burns. The researchers add, "Future clinical trials of resuscitation strategies should include gut microbiome analysis."

Click here to read "The Effect ofBurnResuscitationVolumes on theGutMicrobiomein aSwineModel"

DOI:10.1097/SHK.0000000000001462

###

AboutSHOCK

SHOCK:Injury, Inflammation, and Sepsis: Laboratory and Clinical Approachesincludes studies of novel therapeutic approaches, such as immunomodulation, gene therapy, nutrition, and others. The mission of the Journal is to foster and promote multidisciplinary studies, both experimental and clinical in nature, that critically examine the etiology, mechanisms and novel therapeutics of shock-related pathophysiological conditions.SHOCK is the Official Journal of theShock Society, the European Shock Society, the Indonesian Shock Society, the International Federation of Shock Societies, and the Official and International Journal of the Japan Shock Society

About Wolters Kluwer

Wolters Kluwer is a global leader in professional information, software solutions, and services for the health, tax & accounting, finance, risk & compliance, and legal sectors. We help our customers make critical decisions every day by providing expert solutions that combine deep domain knowledge with specialized technology and services.

Wolters Kluwer reported 2018 annual revenues of 4.3 billion. The group serves customers in over 180 countries, maintains operations in over 40 countries, and employs approximately 18,600 people worldwide. The company is headquartered in AlphenaandenRijn, the Netherlands.

Wolters Kluwer provides trusted clinical technology and evidence-based solutions that engage clinicians, patients, researchers and students with advanced clinical decision support, learning and research and clinical intelligence. For more information about our solutions, visithttp://healthclarity.wolterskluwer.comand follow us onLinkedInand Twitter@WKHealth.

For more information, visitwww.wolterskluwer.com, follow us onTwitter,Facebook,LinkedIn, andYouTube.

Link:
Gut Microbiome Is Altered by Burns, Affected by Fluid Resuscitation: New Evidence in SHOCK - Newswise

Global Nebulizer Market Report 2019 Market Size, Share, Price, Trend and Forecast is a professional and in-depth study on the current state of the global Nebulizer industry.

The report also covers segment data, including: type segment, industry segment, channel segment etc. cover different segment market size, both volume and value. Also cover different industries clients information, which is very important for the manufacturers.

There are 4 key segments covered in this report: competitor segment, product type segment, end use/application segment and geography segment.

Make An EnquiryAbout This Report @ https://www.researchmoz.us/enquiry.php?type=E&repid=2527036&source=atm

For competitor segment, the report includes global key players of Nebulizer as well as some small players.

3A Health CareDeVilbiss HealthcarePHILIPSRossmax International Ltd.CareFusionOmronPARIGFAllied Healthcare Products

Segment by RegionsNorth AmericaEuropeChinaJapanSoutheast AsiaIndia

Segment by TypePneumatic NebulizersUltrasonic NebulizersMesh NebulizersOther

Segment by ApplicationCOPDCystic fibrosisAsthmaOther

Request Sample Report @ https://www.researchmoz.us/enquiry.php?type=S&repid=2527036&source=atm

Important Key questions answered in Nebulizer market report:

What will the market growth rate, Overview, and Analysis by Type of Nebulizer in 2024?

What are the key factors affecting market dynamics? What are the drivers, challenges, and business risks in Nebulizer market?

What is Dynamics, This Overview Includes Analysis of Scope and price analysis of top Manufacturers Profiles?

Who Are Opportunities, Risk and Driving Force of Nebulizer market? Knows Upstream Raw Materials Sourcing and Downstream Buyers.

Who are the key manufacturers in space? Business Overview by Type, Applications, Gross Margin, and Market Share

What are the opportunities and threats faced by manufacturers in the global market?

You can Buy This Report from Here @ https://www.researchmoz.com/checkout?rep_id=2527036&licType=S&source=atm

The content of the study subjects, includes a total of 15 chapters:

Chapter 1, to describe Nebulizer product scope, market overview, market opportunities, market driving force and market risks.

Chapter 2, to profile the top manufacturers of Nebulizer , with price, sales, revenue and global market share of Nebulizer in 2019 and 2015.

Chapter 3, the Nebulizer competitive situation, sales, revenue and global market share of top manufacturers are analyzed emphatically by landscape contrast.

Chapter 4, the Nebulizer breakdown data are shown at the regional level, to show the sales, revenue and growth by regions, from 2019 to 2025.

Chapter 5, 6, 7, 8 and 9, to break the sales data at the country level, with sales, revenue and market share for key countries in the world, from 2019 to 2025.

Chapter 10 and 11, to segment the sales by type and application, with sales market share and growth rate by type, application, from 2019 to 2025.

Chapter 12, Nebulizer market forecast, by regions, type and application, with sales and revenue, from 2019 to 2025.

Chapter 13, 14 and 15, to describe Nebulizer sales channel, distributors, customers, research findings and conclusion, appendix and data source.

Original post:
CNS Gene Therapy Market Projected to Discern Stable Expansion During 2018 2028 - Health News Office

The given report is an excellent research study specially compiled to provide latest insights into critical aspects of the Global Global Gene Therapy for CNS Disorders Market Market by INNOVATE INSIGHTS.

The worldwide market for Global Gene Therapy for CNS Disorders Market is expected to grow at a CAGR of roughly over the next five years, will reach million US$ in 2024, from million US$ in 2019, according to latest industry study.

The Global Global Gene Therapy for CNS Disorders Market Market pursuers will discover this report exceptionally advantageous in comprehension the Market showcase in integrity. The angles and data of the report utilizing figures, structured presentations, pie graphs, and other visual portrayals. This escalates the Global Gene Therapy for CNS Disorders Market Market pictorial portrayal and furthermore helps in getting the Global Gene Therapy for CNS Disorders Market Market business actualities much better. The Global Gene Therapy for CNS Disorders Market Market advertise is probably going to develop at a noteworthy CAGR. The principle goal of report is to direct the client comprehend the Market advertise as far as its definition, order, potential, most recent patterns, and the difficulties that the Global Gene Therapy for CNS Disorders Market Market advertise is confronting.

Key players operating world wide: Gilead (Kite Pharma), Amgen (BioVex), Novartis, Roche (Spark Therapeutics), Bluebird Bio

Premium Sample report of Global Gene Therapy for CNS Disorders Market Market @ https://www.innovateinsights.com/report/global-gene-therapy-for-cns-disorders-market-report/50454/#requestsample

Some key points of Global Gene Therapy for CNS Disorders Market Market research report:

Strategic Developments: The custom analysis gives the key strategic developments of the market, comprising R&D, new product launch, growth rate, collaborations, partnerships, joint ventures, and regional growth of the leading competitors operating in the market on a global and regional scale.

Market Features: The report comprises market features, capacity, capacity utilization rate, revenue, price, gross, production, production rate, consumption, import, export, supply, demand, cost, market share, CAGR, and gross margin. In addition, the report offers a comprehensive study of the market dynamics and their latest trends, along with market segments and sub-segments.

Analytical Tools: The Global Global Gene Therapy for CNS Disorders Market Market report includes the accurately studied and assessed data of the key industry players and their scope in the market by means of a number of analytical tools. The analytical tools such as Porters five forces analysis, feasibility study, and many other market research tools have been used to analyze the growth of the key players operating in the market.

Request inquiry of Report Before Purchasing (Higher Preference For Corporate email ID User): https://www.innovateinsights.com/report/global-gene-therapy-for-cns-disorders-market-report/50454/#buyinginquiry

Segmentation by Product Type: Ex Vivo, In VivoMarket Growth by Applications: Hospitals, Clinics, Others

Benefits of Purchasing Global Gene Therapy for CNS Disorders Market Market Report:

Inimitable Expertise: Analysts will provide deep insights into the reports.Analyst Support: Get your query resolved from our team before and after purchasing the report.Customers Satisfaction: Our team will assist with all your research needs and customize the report.Assured Quality: We focus on the quality and accuracy of the report.

Access complete overview report here: https://www.innovateinsights.com/report/global-gene-therapy-for-cns-disorders-market-report/50454/

This report includes the estimation of market size for value (million US$) and volume (K Units). Both top-down and bottom-up approaches have been used to estimate and validate the market size of Global Gene Therapy for CNS Disorders Market market, to estimate the size of various other dependent submarkets in the overall market.The detail information about In-Depth Analysis, Business opportunities, Market growth rate analysis Available in Full research report.

*If you have any special requirements, please let us know and we will offer you the report as you want.

** The Values marked with XX is confidential data. To know more about CAGR figures fill in your information so that our business development executive can get in touch with you.

Conclusively, This report will provide you a clear view of each and every fact of the market without a need to refer to any other research report or a data source. Our report will provide you with all the facts about the past, present, and future of the concerned Market.

Thanks for reading this article, you can also get separate chapter wise or region wise report versions including North America, Europe or Asia.

For More Information Kindly Contact:Innovate Insights49 Lincoln Highway,Kearny, NJ 07032, USAUnited StatesEmail: [emailprotected]Tel: +1 518 620 4504

Innovate Insights is a large market research firm that has more than just syndicated market research report for the clienteles. Slipping into your shoes, we will be more than happy to serve your need from your point of view. We dont pigeonhole our services and provide customized research services, market advisors, market consultants, market research reports and so much more.

Continue reading here:
Global Gene Therapy for CNS Disorders Market 2019 - Gilead (Kite Pharma), Amgen (BioVex), Novartis, Roche (Spark Therapeutics), Bluebird Bio -...

Global Nebulizer Market Report 2019 Market Size, Share, Price, Trend and Forecast is a professional and in-depth study on the current state of the global Nebulizer industry.

The report also covers segment data, including: type segment, industry segment, channel segment etc. cover different segment market size, both volume and value. Also cover different industries clients information, which is very important for the manufacturers.

There are 4 key segments covered in this report: competitor segment, product type segment, end use/application segment and geography segment.

Make An EnquiryAbout This Report @ https://www.researchmoz.us/enquiry.php?type=E&repid=2527036&source=atm

For competitor segment, the report includes global key players of Nebulizer as well as some small players.

3A Health CareDeVilbiss HealthcarePHILIPSRossmax International Ltd.CareFusionOmronPARIGFAllied Healthcare Products

Segment by RegionsNorth AmericaEuropeChinaJapanSoutheast AsiaIndia

Segment by TypePneumatic NebulizersUltrasonic NebulizersMesh NebulizersOther

Segment by ApplicationCOPDCystic fibrosisAsthmaOther

Request Sample Report @ https://www.researchmoz.us/enquiry.php?type=S&repid=2527036&source=atm

Important Key questions answered in Nebulizer market report:

What will the market growth rate, Overview, and Analysis by Type of Nebulizer in 2024?

What are the key factors affecting market dynamics? What are the drivers, challenges, and business risks in Nebulizer market?

What is Dynamics, This Overview Includes Analysis of Scope and price analysis of top Manufacturers Profiles?

Who Are Opportunities, Risk and Driving Force of Nebulizer market? Knows Upstream Raw Materials Sourcing and Downstream Buyers.

Who are the key manufacturers in space? Business Overview by Type, Applications, Gross Margin, and Market Share

What are the opportunities and threats faced by manufacturers in the global market?

You can Buy This Report from Here @ https://www.researchmoz.com/checkout?rep_id=2527036&licType=S&source=atm

The content of the study subjects, includes a total of 15 chapters:

Chapter 1, to describe Nebulizer product scope, market overview, market opportunities, market driving force and market risks.

Chapter 2, to profile the top manufacturers of Nebulizer , with price, sales, revenue and global market share of Nebulizer in 2019 and 2015.

Chapter 3, the Nebulizer competitive situation, sales, revenue and global market share of top manufacturers are analyzed emphatically by landscape contrast.

Chapter 4, the Nebulizer breakdown data are shown at the regional level, to show the sales, revenue and growth by regions, from 2019 to 2025.

Chapter 5, 6, 7, 8 and 9, to break the sales data at the country level, with sales, revenue and market share for key countries in the world, from 2019 to 2025.

Chapter 10 and 11, to segment the sales by type and application, with sales market share and growth rate by type, application, from 2019 to 2025.

Chapter 12, Nebulizer market forecast, by regions, type and application, with sales and revenue, from 2019 to 2025.

Chapter 13, 14 and 15, to describe Nebulizer sales channel, distributors, customers, research findings and conclusion, appendix and data source.

Original post:
Mannequin-based Simulation Market Insights on Emerging Scope 2026 - Health News Office

Global Nebulizer Market Report 2019 Market Size, Share, Price, Trend and Forecast is a professional and in-depth study on the current state of the global Nebulizer industry.

The report also covers segment data, including: type segment, industry segment, channel segment etc. cover different segment market size, both volume and value. Also cover different industries clients information, which is very important for the manufacturers.

There are 4 key segments covered in this report: competitor segment, product type segment, end use/application segment and geography segment.

Make An EnquiryAbout This Report @ https://www.researchmoz.us/enquiry.php?type=E&repid=2527036&source=atm

For competitor segment, the report includes global key players of Nebulizer as well as some small players.

3A Health CareDeVilbiss HealthcarePHILIPSRossmax International Ltd.CareFusionOmronPARIGFAllied Healthcare Products

Segment by RegionsNorth AmericaEuropeChinaJapanSoutheast AsiaIndia

Segment by TypePneumatic NebulizersUltrasonic NebulizersMesh NebulizersOther

Segment by ApplicationCOPDCystic fibrosisAsthmaOther

Request Sample Report @ https://www.researchmoz.us/enquiry.php?type=S&repid=2527036&source=atm

Important Key questions answered in Nebulizer market report:

What will the market growth rate, Overview, and Analysis by Type of Nebulizer in 2024?

What are the key factors affecting market dynamics? What are the drivers, challenges, and business risks in Nebulizer market?

What is Dynamics, This Overview Includes Analysis of Scope and price analysis of top Manufacturers Profiles?

Who Are Opportunities, Risk and Driving Force of Nebulizer market? Knows Upstream Raw Materials Sourcing and Downstream Buyers.

Who are the key manufacturers in space? Business Overview by Type, Applications, Gross Margin, and Market Share

What are the opportunities and threats faced by manufacturers in the global market?

You can Buy This Report from Here @ https://www.researchmoz.com/checkout?rep_id=2527036&licType=S&source=atm

The content of the study subjects, includes a total of 15 chapters:

Chapter 1, to describe Nebulizer product scope, market overview, market opportunities, market driving force and market risks.

Chapter 2, to profile the top manufacturers of Nebulizer , with price, sales, revenue and global market share of Nebulizer in 2019 and 2015.

Chapter 3, the Nebulizer competitive situation, sales, revenue and global market share of top manufacturers are analyzed emphatically by landscape contrast.

Chapter 4, the Nebulizer breakdown data are shown at the regional level, to show the sales, revenue and growth by regions, from 2019 to 2025.

Chapter 5, 6, 7, 8 and 9, to break the sales data at the country level, with sales, revenue and market share for key countries in the world, from 2019 to 2025.

Chapter 10 and 11, to segment the sales by type and application, with sales market share and growth rate by type, application, from 2019 to 2025.

Chapter 12, Nebulizer market forecast, by regions, type and application, with sales and revenue, from 2019 to 2025.

Chapter 13, 14 and 15, to describe Nebulizer sales channel, distributors, customers, research findings and conclusion, appendix and data source.

More:
Serving numerous end-users, Cladding Panels market anticipated to continue to rise between 2019 2027 - Health News Office

An unexpected early morning phone call from the hospital is never good news. When Joy Johnson answered, her first thought was that Sharon Birzer, her partner of 15 years, was dead. Her fears were amplified by the voice on the other end refusing to confirm or deny it. Just come in and talk to one of the doctors, she remembers the voice saying.

Johnson knew this was a real possibility. A few weeks earlier, she and Birzer sat in the exam room of a lymphoma specialist at Stanford University. Birzers cancer had grown, and fast first during one type of chemotherapy, then through a second. Out of standard options, Birzers local oncologist had referred her for a novel treatment called chimeric antigen receptor T-cell therapy or CAR-T. Birzer and Johnson knew the treatment was risky. They were warned there was a chance of death. There was also a chance of serious complications such as multi-organ failure and neurological impairment. But it was like warning a drowning person that her lifeboat could have problems. Without treatment, the chance of Birzers death was all but certain. She signed the consent form.

Johnson hung up the phone that early morning and sped to the hospital. She met with a doctor and two chaplains in a windowless room in the cancer ward, where happy photos of cancer alumni smiled down from the walls. This is getting worse and worse, Johnson thought. As she remembers it, the doctor went through the timeline of what happened for 10 minutes, explaining how Birzer became sicker and sicker, before Johnson interrupted with the thought splitting her world in two: I need you to tell me whether shes alive or dead.

Birzer wasnt dead. But she was far from okay. The ordeal began with Birzer speaking gibberish. Then came seizures so severe there was concern she wouldnt be able to breathe on her own. When it took a few different medications to stop Birzer from seizing, her doctors sedated her, put a breathing tube down her throat, and connected her to a ventilator. Now, she was unconscious and in the intensive care unit (ICU).

Birzer was one of the early patients to receive CAR-T, a radical new therapy to treat cancer. It involved removing Birzers own blood, filtering for immune cells called T-cells, and genetically engineering those cells to recognise and attack her lymphoma. CAR-T made history in 2017 as the first FDA-approved gene therapy to treat any disease. After three to six months of follow-up, the trials that led to approval showed response rates of 80% and above in aggressive leukemias and lymphomas that had resisted chemotherapy. Patients on the brink of death were coming back to life.

Also read:Rwanda on Track to Become the First Country to Eliminate Cervical Cancer

This is something I often dream of seeing but rarely do. As a doctor who treats cancer, I think a lot about how to frame new treatments to my patients. I never want to give false hope. But the uncertainty inherent to my field also cautions me against closing the door on optimism prematurely. We take it as a point of pride that no field of medicine evolves as rapidly as cancer the FDA approves dozens of new treatments a year.

One of my biggest challenges is staying up to date on every development and teasing apart what should and shouldnt change my practice. I am often a mediator for my patients, tempering theoretical promises with everyday realism. To accept a research finding into medical practice, I prefer slow steps showing me proof of concept, safety, and efficacy.

CAR-T, nearly three decades in the making, systemically cleared these hurdles. Not only did the product work, its approach was also unique among cancer treatments. Unlike our usual advances, this wasnt a matter of prescribing an old drug for a new disease or remixing known medications. CAR-T isnt even a drug. This is a one-time infusion giving a person a better version of her own immune system. When the FDA approved its use, it wasnt a question of whether my hospital would be involved, but how we could stay ahead. We werent alone.

Today, two FDA-approved CAR-T products called Kymriah and Yescarta are available in more than 100 hospitals collectively across the US. Hundreds of clinical trials are tinkering with dosages, patient populations, and types of cancer. Some medical centres are manufacturing the cells on-site.

The FDA approved CAR-T with a drug safety program called a Risk Evaluation and Mitigation Strategy (REMS). As I cared for these patients, I quickly realised the FDAs concerns. Of the 10 or so patients Ive treated, more than half developed strange neurological side effects ranging from headaches to difficulty speaking to seizures to falling unconscious. We scrambled to learn how to manage the side effects in real time.

Johnson and Birzer, who I didnt treat personally but spoke to at length for this essay, understood this better than most. Both had worked in quality control for a blood bank and were medically savvier than the average patient. They accepted a medical system with a learning curve. They were fine with hearing I dont know. Signing up for a trailblazing treatment meant going along for the ride. Twists and bumps were par for the course.

Cancer, by definition, means something has gone very wrong within a cell has malfunctioned and multiplied. The philosophy for fighting cancer has been, for the most part, creating and bringing in treatments from outside the body. Thats how we got to the most common modern approaches: Chemotherapy (administering drugs to kill cancer),radiation(using high energy beams to kill cancer), and surgery (cutting cancer out with a scalpel and other tools). Next came the genetics revolution, with a focus on creating drugs that target a precise genetic mutation separating a cancer cell from a normal one. But cancers are genetically complex, with legions of mutations and the talent to develop new ones. Its rare to have that one magic bullet.

Over the last decade or so, our approach shifted. Instead of fighting cancer from the outside, we are increasingly turning in. The human body is already marvellously equipped to recognise and attack invaders, from the common cold to food poisoning, even if the invaders are ones the body has never seen before. Cancer doesnt belong either.

But since cancer cells come from normal ones, theyve developed clever camouflages to trick and evade the immune system. The 2018 Nobel Prize in Physiology or Medicine was jointly awarded to two researchers for their work in immunotherapy, a class of medications devoted to wiping out the camouflages and restoring the immune systems upper hand. As I once watched a fellow oncologist describe it to a patient: Im not treating you. You are treating you.

What if we could go one step further? What if we could genetically engineer a patients own immune cells to spot and fight cancer, as a sort of best hits of genetic therapy and immunotherapy?

Enter CAR-T. The technology uses T-cells, which are like the bouncers of the immune system. T-cells survey the body and make sure everything belongs. CAR-T involves removing a persons T-cells from her blood and using a disarmed virus to deliver new genetic material to the cells. The new genes given to the T-cells help them make two types of proteins. The first giving the technology its name is a CAR, which sits on the T-cells surface and binds to a protein on the tumour cells surface, like a lock and key.

The second serves as the T-cells caffeine jolt, rousing it to activate. Once the genetic engineering part is done, the T-cells are prodded to multiply by being placed on a rocking device that feeds them nutrients while filtering their wastes. When the cells reach a high enough number a typical dose ranges from hundreds of thousands to hundreds of millions they are formidable enough to go back into the patient. Once inside, the cancer provokes the new cells to replicate even more. After one week, a typical expansion means multiplying by about another 1,000-fold.

Practically, it looks like this: A person comes in for an appointment. She has a catheter placed in a vein, perhaps in her arm or her chest, that connects to a large, whirring machine which pulls in her blood and separates it into its components. The medical team set the T-cells aside to freeze while the rest of the blood circulates back into the patient in a closed loop. Then, the hospital ships the cells frozen to the relevant pharmaceutical companys headquarters or transports them to a lab on-site, where thawing and manufacturing takes from a few days to a few weeks.

When the cells are ready, the patient undergoes about three days of chemotherapy to kill both cancer and normal cells, making room for the millions of new cells and eradicating normal immune players that could jeopardise their existence. She then gets a day or two to rest. When the new cells are infused back into her blood, we call that Day 0.

I remember the first time I watched a patient get his Day 0 infusion. It felt anti-climactic. The entire process took about 15 minutes. The CAR-T cells are invisible to the naked eye, housed in a small plastic bag containing clear liquid.

Thats it? my patient asked when the nurse said it was over. The infusion part is easy. The hard part is everything that comes next.

Once the cells are in, they cant turn off. That this may cause collateral damage was evident from the start. In 2009 working in parallel with other researchers at Memorial Sloan Kettering Cancer Centre in New York and the National Cancer Institute in Maryland oncologists at the University of Pennsylvania opened a clinical trial for CAR-T in human leukaemia patients. (Carl June, who led the CAR-T development, did not respond to Undarks interview request.)

Also read:Explainer: What Is Soft Tissue Cancer?

Of the first three patients who got CAR-T infusions, two achieved complete remission but nearly died in the process. The first was a retired corrections officer named Bill Ludwig, who developed extremely high fevers and went into multi-organ failure requiring time in the ICU. At the time, the medical teams had no idea why it was happening or how to stop it. But time passed. Ludwig got better. Then came the truly incredible part: His cancer was gone.

With only philanthropic support, the trial ran out of funding. Of the eligible patients they intended to treat, the Penn doctors only treated three. So they published the results of one patient in the New England Journal of Medicine and presented the outcomes of all three patients, including Ludwig, at a cancer conference anyway. From there, the money poured in. Based on the results, the Swiss pharmaceutical company Novartis licensed the rights of the therapy.

The next year, six-year-old Emily Whitehead was on the brink of death when she became the first child to receive CAR-T. She also became extremely ill in the ICU, and her cancer was also eventually cured. Her media savvy parents helped bring her story public, making her the poster child for CAR-T. In 2014, the FDA granted CAR-T a breakthrough therapy designation to expedite the development of extremely promising therapies. By 2017, a larger trial gave the treatment to 75 children and young adults with a type of leukaemia B-cell acute lymphoblastic leukaemia that failed to respond to chemotherapy. Eighty-one percent had no sign of cancer after three months.

In August 2017, the FDA approved a CAR-T treatment as the first gene therapy in the US. The decision was unanimous. The Oncologic Drugs Advisory Committee, a branch of the FDA that reviews new cancer products, voted 10 to zero in favour of Kymriah. Committee members called the responses remarkable and potentially paradigm changing. When the announcement broke, a crowd formed in the medical education centre of Penn Medicine, made up of ecstatic faculty and staff. There were banners and T-shirts. A remarkable thing happened was the tagline, above a cartoon image of a heroic T-cell.

Two months later, in October 2017, the FDA approved a second CAR-T formulation called Yescarta from Kite Pharma, a subsidiary of Gilead Sciences, to treat an aggressive blood cancer in adults called diffuse large B-cell lymphoma, the trial of which had shown a 54 percent complete response rate, meaning all signs of cancer had disappeared. In May 2018, Kymriah was approved to treat adults with non-Hodgkin lymphoma.

That year, the American Society of Clinical Oncology named CAR-T the Advance of the Year, beating out immunotherapy, which had won two years in a row. When I attended the last American Society of Hematology meeting in December 2018, CAR-T stole the show. Trying to get into CAR-T talks felt like trying to get a photo with a celebrity. Running five minutes late to one session meant facing closed doors. Others were standing room only.

With every slide, it became difficult to see over a sea of smartphones snapping photos. At one session I found a seat next to the oncologist from my hospital who treated Birzer. Look, she nudged me. Do you see all these non-member badges? I turned. Members were doctors like us who treated blood cancers. I couldnt imagine who else would want to be here. Who are they? I asked. Investors, she said. It felt obvious the moment she said it.

For patients, the dreaded c word is cancer. For oncologists, its cure. When patients ask, Ive noticed how we gently steer the conversation toward safer lingo. We talk about keeping the cancer in check. Cure is a dangerous word, used only when so much time has passed from her cancer diagnosis we can be reasonably certain its gone. But that line is arbitrary. We celebrate therapies that add weeks or months because the diseases are pugnacious, the biology diverse, and the threat of relapse looming. Oncologists are a tempered group, or so Ive learned, finding inspiration in slow, incremental change.

This was completely different. These were patients who would have otherwise died, and the trials were boasting that 54 to 81 percent were cancer-free upon initial follow-up. PET scans showed tumours that had speckled an entire body melt away. Bone marrow biopsies were clear, with even the most sensitive testing unable to detect disease.

The dreaded word was being tossed around could this be the cure weve always wanted?

When a new drug gets FDA approval, it makes its way into clinical practice, swiftly and often with little fanfare. Under the drug safety program REMS, hospitals offering CAR-T were obligated to undergo special training to monitor and manage side effects. As hospitals worked to create CAR-T programs, oncologists like me made the all too familiar transition from first-time user to expert.

It was May 2018 when I rotated through my hospitals unit and cared for my first patients on CAR-T. As I covered 24-hour shifts, I quickly learned that whether I would sleep that night depended on how many CAR-T patients I was covering. With each treatment, it felt like we were pouring gasoline on the fire of patients immune systems. Some developed high fevers and their blood pressures plummeted, mimicking a serious infection. But there was no infection to be found. When resuscitating with fluids couldnt maintain my patients blood pressures, I sent them to the ICU where they required intensive support to supply blood to their critical organs.

We now have a name for this effect cytokine release syndrome that occurs in more than half of patients who receive CAR-T, starting with Ludwig and Whitehead. The syndrome is the collateral damage of an immune system on the highest possible alert. This was first seen with other types of immunotherapy, but CAR-T took its severity to a new level. Usually starting the week after CAR-T, cytokine release syndrome can range from simple fevers to multi-organ failure affecting the liver, kidneys, heart, and more. The activated T-cells make and recruit other immune players called cytokines to join in the fight. Cytokines then recruit more immune cells. Unlike in the early trials at Penn, we now have two medicines to dampen the effect. Steroids calm the immune system in general, while a medication called tocilizumab, used to treat autoimmune disorders such as rheumatoid arthritis, blocks cytokines specifically.

Also read:The DNA Detectives Hunting the Causes of Cancer

Fortuity was behind the idea of tocilizumab: When Emily Whitehead, the first child to receive CAR-T, developed cytokine release syndrome, her medical team noted that her blood contained high levels of a cytokine called interleukin 6. Carl June thought of his own daughter, who had juvenile rheumatoid arthritis and was on a new FDA-approved medication that suppressed the same cytokine. The team tried the drug, tocilizumab, in Whitehead. It worked.

Still, we were cautious in our early treatments. The symptoms of cytokine release syndrome mimic the symptoms of severe infection. If this were infection, medicines that dampen a patients immune system would be the opposite of what youd want to give. There was another concern: Would these medications dampen the anti-cancer activity too? We didnt know. Whenever a CAR-T patient spiked a fever, I struggled with the question is it cytokine release syndrome, or is it infection? I often played it safe and covered all bases, starting antibiotics and steroids at the same time. It was counterintuitive, like pressing both heat and ice on a strain, or treating a patient simultaneously with fluids and diuretics.

The second side effect was even scarier: Patients stopped talking. Some, like Sharon Birzer spoke gibberish or had violent seizures.Some couldnt interact at all, unable to follow simple commands like squeeze my fingers. How? Why? At hospitals across the nation, perfectly cognitively intact people who had signed up to treat their cancer were unable to ask what was happening.

Our nurses learned to ask a standardised list of questions to catch the effect, which we called neurotoxicity: Where are we? Who is the president? What is 100 minus 10? When the patients scored too low on these quizzes, they called me to the bedside.

In turn, I relied heavily on alaminated booklet, made by other doctors who were using CAR-T, which we tacked to a bulletin board in our doctors workroom. It contained a short chart noting how to score severity and what to do next. I flipped through the brightly colour-coded pages telling me when to order a head CT-scan to look for brain swelling and when to place scalp electrodes looking for seizures. Meanwhile, we formed new channels of communication. As I routinely called a handful of CAR-T specialists at my hospital in the middle of the night, national consortiums formed where specialists around the country shared their experiences. As we tweaked the instructions, we scribbled updates to the booklet in pen.

I wanted to know whether my experience was representative. I came across an abstract and conference talk that explored what happened to 277 patients who received CAR-T in the real world, so I emailed the lead author, Loretta Nastoupil, director of the Department of Lymphoma and Myeloma at the University of Texas MD Anderson Cancer Center in Houston. Fortuitously, she was planning a trip to my university to give a talk that month. We met at a caf and I asked what her research found. Compared to the earlier trials, the patients were much sicker, she said. Of the 277 patients, more than 40 percent wouldnt have been eligible for the very trials that got CAR-T approved. Was her team calling other centres for advice? They were calling us, she said.

Patients included in clinical trials are carefully selected. They tend not to have other major medical problems, as we want them to survive whatever rigorous new therapy we put them through. Nastoupil admits some of it is arbitrary. Many criteria in the CAR-T trials were based on criteria that had been used in chemotherapy trials. These become standard languages that apply to all studies, she said, listing benchmarks like a patients age, kidney function, and platelet count. But we have no idea whether criteria for chemotherapy would apply to cellular therapy.

Now, with a blanket FDA approval comes clinical judgement. Patients want a chance. Oncologists want to give their patients a chance. Young, old, prior cancer, heart disease, or liver disease without strict trial criteria, anyone is fair game.

When I was making rounds at my hospital, I never wandered too far from these patients rooms, medically prepared for them to crash at any moment. At the same time, early side effects made me optimistic. A bizarre truism in cancer is that side effects may bode well. They could mean the treatment is working. Cancer is usually a waiting game, requiring months to learn an answer. Patients and doctors alike seek clues, but the only real way to know is waiting: Will the next PET scan show anything? What are the biopsy results?

CAR-T was fundamentally different from other cancer treatments in that it worked fast. Birzers first clue came just a few hours after her infusion. She developed pain in her lower back. She described it as feeling like she had menstrual cramps. A heavy burden of lymphoma lay in her uterus. Could the pain mean that the CAR-T cells had migrated to the right spot and started to work? Her medical team didnt know, but the lead doctors instinct was that it was a good sign.

Two days later, her temperature shot up to 102. Her blood pressure dropped. The medical team diagnosed cytokine release syndrome, as though right on schedule, and gave her tocilizumab.

Every day, the nurses would ask her questions and have her write simple sentences on a slip of paper to monitor for neurotoxicity. By the fifth day, her answers changed. She started saying things that were crazy, Johnson explained.

One of Birzers sentences was guinea pigs eat greens like hay and pizza. Birzer and Johnson owned two guinea pigs, so their diet would be something Birzer normally knew well. So Johnson tried to reason with her: They dont eat pizza. And Birzer replied, They do eat pizza, but only gluten-free.

Johnson remembers being struck by the certainty in her partners delirium. Not only was Birzer confused, she was confident she was not. She was doubling down on everything, Johnson described. She was absolutely sure she was right.

Johnson vividly remembers the evening before the frightening early-morning phone call that brought her rushing back to the hospital. Birzer had said there was no point in Johnson staying overnight; she would only watch her be in pain. So Johnson went home. After she did, the doctor came by multiple times to evaluate Birzer. She was deteriorating and fast. Her speech became more and more garbled. Soon she couldnt name simple objects and didnt know where she was. At 3 a.m., the doctor ordered a head CT to make sure Birzer wasnt bleeding into her brain.

Also read:Bankrupt, Poorly Educated Cancer Patients Forced to Live on Street Outside Mumbai Hospital

Fortunately, she wasnt. But by 7 a.m. Birzer stopped speaking altogether. Then she seized. Birzers nurse was about to step out of the room when she noticed Birzers arms and legs shaking. Her eyes stared vacantly and she wet the bed. The nurse called a code blue, and a team of more doctors and nurses ran over. Birzer was loaded with high-dose anti-seizure medications through her IV. But she continued to seize. As nurses infused more medications into her IV, a doctor placed a breathing tube down her throat.

Birzers saga poses the big question: Why does CAR-T cause seizures and other neurological problems? No one seemed to know. My search of the published scientific literature was thin, but one name kept cropping up. So I called her. Juliane Gust, a paediatric neurologist and scientist at Seattle Childrens Hospital, told me her investigations of how CAR-T affects the brain were motivated by her own experiences. When the early CAR-T trials opened at her hospital in 2014, she and her colleagues began getting calls from oncologists about brain toxicities they knew nothing about. Where are the papers? she remembered thinking. There was nothing.

Typically, the brain is protected by a collection of cells aptly named the blood-brain-barrier. But with severe CAR-T neurotoxicity, research suggests, this defence breaks down. Gust explained that spinal taps on these patients show high levels of cytokines floating in the fluid surrounding the spine and brain. Some CAR-T cells circulate in the fluid too, she said, but these numbers do not correlate with sicker patients. CAR-T cells are even seen in the spinal fluid of patients without any symptoms.

What does this mean? Gust interprets it as a patients symptoms having more to do with cytokines than the CAR-T cells. Cytokine release syndrome is the number one risk factor for developing neurotoxicity over the next few days, she said. The mainstay for neurotoxicity is starting steroids as soon as possible. In the beginning we didnt manage as aggressively. We were worried about impairing the function of the CAR-T, she added. Now we give steroids right away.

But the steroids dont always work. Several doses of steroids didnt prevent Birzer from seizing. The morning after Johnsons alarming phone call, after the meeting at the hospital when she learned what had happened, a chaplain walked her from the conference room to the ICU. The first day, Johnson sat by her partners bedside while Birzer remained unconscious. By the next evening, she woke up enough to breathe on her own. The doctors removed her breathing tube, and Birzer looked around. She had no idea who she was or where she was.

Birzer was like a newborn baby, confused and sometimes frightened by her surroundings. She frequently looked like she was about to say something, but she couldnt find the words despite the nurses and Johnsons encouragement. One day she spoke a few words. Eventually she learned her name. A few days later she recognised Johnson. Her life was coming back to her, though she was still suspicious of her reality. She accused the nurses of tricking her, for instance, when they told her Donald Trump was president.

She took cues from the adults around her on whether her actions were appropriate. The best example of this was her I love you phase. One day, she said it to Johnson in the hospital. A few nurses overheard it and commented on how sweet it was. Birzer was pleased with the reaction. So she turned to the nurse: I love you! And the person emptying the trash: I love you! Months later, she was having lunch with a friend who asked, Do you remember when you told me you loved me? Birzer said, Well, I stand by that one.

When she got home, she needed a walker to help with her shakiness on her feet. When recounting her everyday interactions, she would swap in the wrong people, substituting a friend for someone else. She saw bugs that didnt exist. She couldnt hold a spoon or a cup steady. Johnson would try to slow her down, but Birzer was adamant she could eat and drink without help. Then peas would fly in my face, Johnson said.

Patients who experience neurotoxicity fall into one of three categories. The majority are impaired but then return to normal without long-term damage. A devastating handful, less than 1 percent, develop severe brain swelling and die. The rest fall into a minority that have lingering problems even months out. These are usually struggles to think up the right word, trouble concentrating, and weakness, often requiring long courses of rehabilitation and extra help at home.

As Birzer told me about her months of rehab, I thought how she did seem to fall somewhere in the middle among the patients Ive treated. On one end of the spectrum was the rancher who remained profoundly weak a year after his infusion. Before CAR-T, he walked across his ranch without issue; six months later, he needed a walker. Even with it, he fell on a near weekly basis. On the other end was the retired teacher who couldnt speak for a week she would look around her ICU room and move her mouth as though trying her hardest and then woke up as though nothing happened. She left the hospital and instantly resumed her life, which included a recent trip across the country. In hindsight, I remember how we worried more about giving the therapy to the teacher than the rancher, as she seemed frailer. Outcomes like theirs leave me with a familiar humility I keep learning in new ways as a doctor: We often cant predict how a patient will do. Our instincts can be just plain wrong.

I asked Gust if we have data to predict who will land in which group. While we can point to some risk factors higher burdens of cancer, baseline cognitive problems before therapy the individual patient tells you nothing, she confirmed.

Also read:Why Everyone Around You Seems to Be Getting Cancer

So we wait.

Doctors like me who specialise in cancer regularly field heart-wrenching questions from patients. They have read about CAR-T in the news, and now they want to know: What about me? What about my cancer?

So, who gets CAR-T? That leads to the tougher question who doesnt? That depends on the type of cancer and whether their insurance can pay.

CAR-T is approved to treat certain leukaemias and lymphomas that come from the blood and bone marrow. Since the initial approval, researchers have also set up new CAR-T trials for all sorts of solid tumours from lung cancer to kidney cancer to sarcoma. But progress has been slow. While some promising findings are coming from the lab and in small numbers of patients on early phase trials, nothing is yet approved in humans. The remarkable responses occurring in blood cancers just werent happening in solid tumours.

Cancer is one word, but its not one disease. Its easier to prove why something works when it works than show why it doesnt work when it doesnt work, said Saar Gill, a hematologist and scientist at the University of Pennsylvania who co-founded a company called Carisma Therapeutics using CAR-T technology against solid tumours. That was his short answer, at least. The longer answer to why CAR-T hasnt worked in solid cancers involves what Gill believes are two main barriers. First, its a trafficking problem. Leukaemia cells tend to be easier targets; they bob through the bloodstream like buoys in an ocean. Solid tumours are more like trash islands. The cancer cells stick together and grow an assortment of supporting structures to hold the mound together. The first problem for CAR-T is that the T-cells may not be able to penetrate the islands. Then, even if the T-cells make it in, theyre faced with a hostile environment and will likely die before they can work.

At Carisma, Gill and his colleagues look to get around these obstacles though a different immune cell called the macrophage. T-cells are not the only players of the immune system, after all. Macrophages are gluttonous cells that recognise invaders and engulf them for destruction. But studies have shown they cluster in solid tumours in a way T-cells dont. Gill hopes genetically engineered macrophages can be the stowaways that sneak into solid tumour and attack from the inside out.

Another big challenge, even for leukaemias and lymphomas, is resistance, where the cancers learn to survive the CAR-T infusion. While many patients in the trials achieved remission after a month, we now have two years worth of data and the outlook isnt as rosy. For lymphoma, that number is closer to 40 percent. Patients celebrating cures initially are relapsing later. Why?

The CAR-T cells we use target a specific protein on cancer cells. But if the cancer no longer expresses that protein, that can be a big problem, and were finding thats exactly whats happening. Through blood testing, we see that many patients who relapse lose the target.

Researchers are trying to regain the upper hand by designing CAR-Ts to target more than one receptor. Its an old idea in a new frame: An arms race between our medicines and the illnesses that can evolve to evade them. Too much medical precision in these cases is actually not what we want, as it makes it easier for cancer to pinpoint whats after it and develop an escape route. So, the reasoning goes, target multiple pieces at once. Confuse the cancer.

Then theres the other dreaded c word: Cost. Novartis Kymriah runs up to $475,000 while Kite Pharmas Yescarta is $373,000. That covers manufacturing and infusion. Not included is the minimum one-week hospital stay or any complications.

They are daunting numbers. Some limitations on health care we accept maybe the patients are too sick; maybe they have the wrong disease. The wrong cost is not one we as a society look kindly upon. And drug companies shy away from that kind of attention.

Cost origins in medicine are notoriously murky. Novartis, confident in its technology, made an offer to offset the scrutiny in CAR-T. If the treatment didnt work after one month, the company said it wouldnt send a bill.

Not everyone agrees that cost is an issue. Gill, for example, believes the concern is over-hyped. Its not a major issue, he told me over the phone. Look, of course [with] health care in this country, if you dont have insurance, then youre screwed. That is no different when it comes to CAR-T as it is for anything else, he said. The cost conversation must also put CAR-T in context. Gill went on to list what these patients would be doing otherwise months of chemotherapy, bone marrow transplants, hospital stays for cancer-associated complications and the associated loss of income as patients and caregivers miss work. These could add up to far more than a one-time CAR-T infusion. A bone marrow transplant, for example, can cost from $100,000 to more than $300,000. The cancer-fighting drug blinatumomab, also used to treat relapsed leukaemia, costs $178,000 a year. Any discussion of cost is completely irresponsible without weighing the other side of the equation, Gill said.

Also read:Many Women With Breast Cancer May Not Need Chemo, But Beware Misleading Headlines

How the system will get on board is another question. Logistics will be an issue, Gill conceded. The first national Medicare policy for covering CAR-T was announced in August 2019, two years after the first product was approved. The Centres for Medicare and Medicaid Services has offered to reimburse a set rate for CAR T-cell infusion, and while this figure was recently raised, it remains less than the total cost. Despite the expansion of medical uses, at some centres referrals for CAR-T are dropping as hospitals worry its a net loss. And while most commercial insurers are covering CAR-T therapies, companies less accustomed to handling complex therapies can postpone approval. Ironically, the patients considering CAR-T are the ones for whom the window for treatment is narrowest. A delay of even a few weeks can mean the difference between a cure and hospice.

This, of course, poses a big problem. A breakthrough technology is only as good as its access. A major selling point of CAR-T besides the efficacy is its ease. Its a one-and-done treatment. Engineered T-cells are intended to live indefinitely, constantly on the alert if cancer tries to come back. Compare that to chemotherapy or immunotherapy, which is months of infusions or a pill taken indefinitely. CAR-T is more akin to surgery: Cut it out, pay the entire cost upfront, and youre done.

Birzer was lucky in this respect. I asked her and Johnson if cost had factored into their decision to try CAR-T. They looked at each other. It wasnt an issue, said Johnson. They remembered getting a statement in the mail for a large sum when they got home. But Birzer had good insurance. She didnt pay a cent.

One year after Birzers infusion, I met her and Johnson at a coffee shop near their home in San Francisco. They had saved a table. Johnson had a newspaper open. Birzer already had her coffee, and I noticed her hand trembling as she brought it to her mouth. She described how she still struggles to find exactly the right words. She sometimes flings peas. But shes mostly back to normal, living her everyday life. She has even returned to her passion, performing stand-up comedy, though she admitted that at least for general audiences: My jokes about cancer didnt kill.

People handed a devastating diagnosis dont spend most of their time dying. They are living, but with a heightened awareness for a timeline the rest of us take for granted. They sip coffee, enjoy their hobbies, and read the news while also getting their affairs in order and staying on the lookout, constantly, for the next treatment that could save them.

Hoping for a miracle while preparing to die are mutually compatible ideas. Many of my patients have become accustomed to living somewhere in that limbo. It is humbling to witness. They hold out hope for a plan A, however unlikely it may be, while also adjusting to the reality of a plan B. They live their lives; and they live in uncertainty.

I see patients in various stages of this limbo. In clinic, I met a man with multiple myeloma six months after a CAR-T trial that supposedly cured him. He came in with a big smile but then quietly began praying when it was time to view PET results. He asked how the other patients on the trial were doing, and I shared the stats. While percentages dont say anything about an individual experience, theyre also all patients have to go on. When someone on the same treatment dies, its shattering for everyone. Was one person the exception, or a harbinger anothers fate? Who is the outlier?

I look at these patients and think a sober truth: Before CAR-T, all would likely die within six months. Now, imagine taking 40 percent and curing them. Sure, a naysayer might point out, its only 40 percent. Whats the hype if most still succumb to their cancer? But there was nothing close to that before CAR-T. I agree with how Gill described it: I think CAR-T cells are like chemotherapy in the 1950s. Theyre not better than chemotherapy theyre just different. For an adversary as tough as cancer, well take any tool we can get.

There remain many questions. Can we use CAR-T earlier in a cancers course? Lessen the side effects? Overcome resistance? Streamline manufacturing and reimbursement? Will it work in other cancers? Patients will sign up to answer.

For now, Birzer seems to be in the lucky 40%. Her one-year PET scan showed no cancer. I thought of our last coffee meeting, where I had asked if she ever worried she wouldnt return to normal. She didnt even pause. If youre not dead, she said, youre winning.

This article was originally published on Undark. Read the original article.

More:
Behind the Scenes of a Radical New Cancer Cure - The Wire

Global Nebulizer Market Report 2019 Market Size, Share, Price, Trend and Forecast is a professional and in-depth study on the current state of the global Nebulizer industry.

The report also covers segment data, including: type segment, industry segment, channel segment etc. cover different segment market size, both volume and value. Also cover different industries clients information, which is very important for the manufacturers.

There are 4 key segments covered in this report: competitor segment, product type segment, end use/application segment and geography segment.

Make An EnquiryAbout This Report @ https://www.researchmoz.us/enquiry.php?type=E&repid=2527036&source=atm

For competitor segment, the report includes global key players of Nebulizer as well as some small players.

3A Health CareDeVilbiss HealthcarePHILIPSRossmax International Ltd.CareFusionOmronPARIGFAllied Healthcare Products

Segment by RegionsNorth AmericaEuropeChinaJapanSoutheast AsiaIndia

Segment by TypePneumatic NebulizersUltrasonic NebulizersMesh NebulizersOther

Segment by ApplicationCOPDCystic fibrosisAsthmaOther

Request Sample Report @ https://www.researchmoz.us/enquiry.php?type=S&repid=2527036&source=atm

Important Key questions answered in Nebulizer market report:

What will the market growth rate, Overview, and Analysis by Type of Nebulizer in 2024?

What are the key factors affecting market dynamics? What are the drivers, challenges, and business risks in Nebulizer market?

What is Dynamics, This Overview Includes Analysis of Scope and price analysis of top Manufacturers Profiles?

Who Are Opportunities, Risk and Driving Force of Nebulizer market? Knows Upstream Raw Materials Sourcing and Downstream Buyers.

Who are the key manufacturers in space? Business Overview by Type, Applications, Gross Margin, and Market Share

What are the opportunities and threats faced by manufacturers in the global market?

You can Buy This Report from Here @ https://www.researchmoz.com/checkout?rep_id=2527036&licType=S&source=atm

The content of the study subjects, includes a total of 15 chapters:

Chapter 1, to describe Nebulizer product scope, market overview, market opportunities, market driving force and market risks.

Chapter 2, to profile the top manufacturers of Nebulizer , with price, sales, revenue and global market share of Nebulizer in 2019 and 2015.

Chapter 3, the Nebulizer competitive situation, sales, revenue and global market share of top manufacturers are analyzed emphatically by landscape contrast.

Chapter 4, the Nebulizer breakdown data are shown at the regional level, to show the sales, revenue and growth by regions, from 2019 to 2025.

Chapter 5, 6, 7, 8 and 9, to break the sales data at the country level, with sales, revenue and market share for key countries in the world, from 2019 to 2025.

Chapter 10 and 11, to segment the sales by type and application, with sales market share and growth rate by type, application, from 2019 to 2025.

Chapter 12, Nebulizer market forecast, by regions, type and application, with sales and revenue, from 2019 to 2025.

Chapter 13, 14 and 15, to describe Nebulizer sales channel, distributors, customers, research findings and conclusion, appendix and data source.

Read more:
Leading Manufacturers and their Strategies to see Distinctly Growth in Antidiuretic Drugs Market by 2025 - Health News Office

A two-time cancer survivor learns more about pancreatic cysts and discusses the value and cautions of genetic testing.

Barbara Tako is a breast cancer survivor (2010), melanoma survivor (2014) and author of Cancer Survivorship Coping ToolsWe'll Get You Through This. She is a cancer coping advocate, speaker and published writer for television, radio and other venues across the country. She lives, survives, and thrives in Minnesota with her husband, children and dog. See more at http://www.cancersurvivorshipcopingtools.com,or http://www.clutterclearingchoices.com.

Intraductal Papillary Mucosal Neoplasms in my pancreas are the latest "lovely" thing that cancer has brought into my life. Well, it is not my first time around - I have already had breast cancer and melanoma. My particular IPMNs may not be or ever become cancer, and yet they subject me to play the "wait and watch game" with one more cancer-type thing.

If you are a cancer survivor, you know how that gameworks - try to move forward with life while not pre-worrying too much. How were my IPMNs found? I had a screening MRI because of my PALB2 genetic cancer mutation. Sometimes IPMNs are found by accident when having an MRI for an unrelated reason. Gotta love technology!

The way one doctor worded it, I was fortunate to have the PALB2 genetic mutation that prompted the MRI that caught these three IPMNs so early and will result in continued monitoring. Cancer survivors all learn that cancers caught early often have better outcomes than cancers that have already grown and spread. Pancreatic cancer has a poor survival ratebecause it is often caught too late. There is a moral to that story that I want to shout from the rooftops: Please, please see a geneticist and have genetic testing done!

Still, there is a potential dark side to genetic testing. It sounds like if a person has a genetic finding and wants to have children, they may be able to screen out embryos that get the mutation before implanting them. Hm. Hey wait a minute:I would have been one of those screened-out embryos if the technology had existed back in that day and my parents had chosen that route. So, yes, genetic testing is a choice,but meeting with a genetic counselor before the testing is decided upon is also very important.

There are many questions to consider before even getting testing done. To test or not to test? How much do you want to know? What happens once that knowledge is out there?A person can't be discriminated against for health care due to genetic test results, but life or disability insurancecoverage, among others, may be a different story. Also, if you choose genetic testing, how often do you go back and get re-tested? Exciting advances are happening rapidly in this field. When I first got tested nine years ago, they only tested a couple of breast cancer genetic mutations. My latest genetic test looked for nineteen mutations - and found my PALB2!

Of course in my case, I GoogledIPMNs and learned lots of frightening stuff before I met with the pancreas specialist. For IPMNs, location and size matter, and I am fortunate that mine are very small and not in worrisome locations. They are also too small for fine needle aspiration or surgery. I will have another MRI in about a year to watch for changes. This means that if they do start to appear cancerous, I may have surgical options to consider which might, in my case, provide a better prognosis than usual for pancreatic cancer.

Genetic testing leaves me optimistic, grateful, and yes, cautious. Please be careful out there, make thoughtful choices, and be sure your sources of information are reliable.

Follow this link:
Things to Consider in Genetic Testing - Curetoday.com

If youre a dog owner, you can buy your pet bespoke treats, you can put them in a red vest and take them everywhere you go, and you can accessorize them to the hilt. Cats rarely get in on this fun (only a self-hating feline will allow the application of a costume), so the industry tends to leave them behindwhich is probably just what they want.

Look, we get it. Your dog loves you and is your proverbial best friend. Cats are cruel and soulless. And yet, millions of us simply prefer the company of felines, and its not just because your dog smells bad and drools all over the place. Its just in our DNA.

Speaking of which, while dog owners have scads of options for testing their pups DNA, cat owners have largely been left out in the cold by the genetic testing industry. And while most cat owners arent dying to get on the cloning bandwagon the way dog owners are, that doesnt mean we dont want to know more about our pets heritage and health, even if science could care less.

We have two cats, but when my wife and I talk about genetic questions, they revolve around Saffy, our 6-year-old specimen who most would charitably describe as a mix. Shes about eight different colors, with an orange splotch on her back and another on one ear. Equally charitably, one would say she is eccentric. Few believe me when I say that she spends all day in our bed, under the covers. I mean all day: She crawls in around 8 am and doesnt come out until 5 pm. And she is absolutely terrified of everything. If a delivery driver pulls into the driveway during her awake hours, she runs to the safety of the covers. The doorbell throws her into a full-on panic. My wife says shes a babe.

Photograph: Susanne Bergstrom Null

I write all of this because I have a lot of questions about Saffy. What kind of cat(s) is she? And why is she such a freak? Could it be a medical condition?

Enter Basepaws, one of a very small number of services that promise to sequence your kittys DNA, revealing information about both breed and ancestry as well as scanning for numerous markers that could indicate elevated risks for certain diseases. If youve ever taken a human DNA test, you know how this goes. You swab the inside of your cats mouthnot hard if you have a helperand drop the swab into a test tube. You then mail it off to Basepaws and wait for the results to come back.

We swabbed, mailed, and waited, and eventually I received Basepaws report in two pieces. First came the health results, then the genetic report was later appended to it. The report takes the form of a massive PDF34 pages long for lil Saffand it certainly feels full of information. The health data is weighty, including information on 17 diseases based on 39 genetic markers. I was surprised, but happy, to see that Saffy was in the clear on all of them, with no risks noted. She wasnt even a carrier of any genes that would put her at risk of disease, though Saffys clearly not meant for breeding. From polycystic kidney disease to mucopolysaccharidosis, Saffy appears to be free of major ailments and is destined to have a long and happy life ahead of her, safely tucked away in bed.

The breed report is somewhat more complex and is indicative of the general lack of available scientific information about cat breeds and ancestry. An introduction in the report notes that cats are comparably wild in comparison to dogs and other animals, that theyve not changed all that much in thousands of years. And while cat breeds are definitely a thing, by and large cats just arent bred nearly as much as dogs are. The result: 95 percent of cats in the world are of mixed breed, referred to in the report as polycat.

Polycat doesnt mean a mix of a couple of known breeds, it basically means a mix of all the breeds. Its the common part of the genome that the reference genome (felis_catus_9.0) doesnt really have enough information about. The genes in the polycat segment could relate to Russian Blue, or they could be Egyptian Mau. They just dont know yet. Sure enough, Saffys reportand I expect most reportspeg her at nearly 46 percent polycat.

The rest of the report is where the fun is, with Basepaws breaking down the breeds into four major groups: Western, Eastern, Persian, and Exotic. Saffys other 56 percent has traits related to all four of these groups, and her mix of those groups is roughly 37, nine, six, and three percent, respectively. Basepaws then breaks down those four breed groups by detailing three to seven cat breeds within each. These are ranked based on similarity to your cat, though you dont exactly get a specific breakdown like you do with, say, Ancestry.com. While Basepaws tells me Saffy is mostly Burmese within that 9 percent Eastern group, theres no estimate that shes, say, 6 percent Burmese overall, which would be a lot more fun.

Photograph: Basepaws

Basepaws does get to this information in a sort-of roundabout way in full-page descriptions of each of the top four sub-breeds under the four main categories. So for Saffy, that was American Shorthair (of course), Burmese, Bengal, and Exotic Shorthair. On the relevant page, Basepaws tells me that Saffy is more similar to the American Shorthair than 72.76 percent of all other cats in our database. Thats interesting, but it ultimately tells me more about the Basepaws database than Saffys genetics. Shes 54.67 percent more similar to a Burmese than all the other cats in the Basepaws database yet only 9 percent of her genetics are even in that family. In fact shes also more similar to both Bengal and Exotic Shorthair than more than 50 percent of cats in the database, which would seem to indicate shes got a lot of different cat types in her. Essentially shes the everything bagel of cats.

The Basepaws report can be a bit confusing, and it doesnt feel complete in large part because it cant be complete. Theres just not enough information about cat breeds available to make for a full picture. Basepaws notes that as it collects more data, it will be able to chip away at that polycat component, though some updates will cost extra (pricing is still being worked out).

As curious as the Basepaws report is, the company still seems to be having some growing pains. It took two months for the health report to come in, and nearly another month to receive Saffys genetic profile. Thats a long time. In cat years thats like 18 months.

At $99, Basepaws is priced the same as AncestryDNA (for people), though its still the least expensive and seemingly the most full-featured cat DNA testing product on the market. HomeDNAs Cat DNA kit runs $125; Optimal Selection has a $100 kit targeted mainly at breeders, and those are the only other options Ive been able to find. Any way you cut it, DNA testing your kitty is a pricey affair, though those concerned about hereditary diseases may find the added peace of mind more than worth it.

Your cat, of course, could not care less.

Basepaws' Cat DNA test is available directly from the company's website, or from Amazon.

See the original post:
Basepaws' $99 Cat DNA Test Tells You What's Truly Wrong With Your Cat - WIRED

DNA testing giant Ancestry.com LLC is entering the growing and potentially lucrative field of genetic health screenings with a strategy thats markedly different from that of its biggest competitor.

Ancestry said last Tuesday that its new consumer health tests an area the genealogy-focused company has been slow to embrace will require authorization by a physician.

Its main competitor, 23andMe Inc., went through the lengthy and expensive process of getting approval from the U.S. Food and Drug Administration so it can sell its tests directly to customers without a prescription.

The involvement of doctors in Ancestrys tests places it in the midst of a debate over whether physician-ordered genetic screening is merely a way for companies to avoid the regulatory scrutiny of the FDA. Several other DNA startups, including Color and Veritas, also require a doctor to order health tests.

The FDA hasnt intervened in the field of physician-ordered genetic tests, although it has signaled an intent to do so. So far, a doctors involvement has been considered enough protection for consumers, even if a patient has little interaction with the physician. Its unclear whether the entrance of a major player like Ancestry might change that.

I suspect that FDA is going to eventually do something as these tests begin to enter our world in a big way, said Robert Cook-Deegan, a professor at the University of Arizona who studies genome ethics and the law.

Ancestry Chief Executive Officer Margo Georgiadis said the company wanted to focus on providing ways for its tests to integrate easily into the care patients receive from their regular doctors.

Thats really why we chose a path that has a doctor, she said, so that the consumer not only can find out a risk factor, but they can seamlessly take a lab report with clinically recommended guidelines into the doctors office so that theres a clear next path for action.

After ordering a health DNA test from Ancestry, customers must fill out a brief medical history survey, which Ancestry then funnels to an outside network of doctors and genetic counselors employed by PWNHealth LLC to approve the test.

Once the results are in, those doctors review them and make sure that patients receive the appropriate educational materials alongside their results. For example, if results show a harmful variant of the BRCA 1 or 2 genes, a customer would receive a video explaining hereditary breast and ovarian cancer syndrome. Its a model similar to that followed by other genetic-testing companies.

Ancestrys health tests include free access to a genetic counselor. And before disclosing potentially troubling results, the company requires consumers to watch educational material about the condition. The reports also include clinical reports that a customer can share with their doctor.

If you have a finding thats important, you will have all the tools you need to learn more about it, said Catherine Ball, Ancestrys chief scientific officer.

But according to Cook-Deegan, the university professor, most consumers may not understand the limitations of the test.

A lot of whether this is a good thing or a bad thing depends on the quality of their testing, he said. It depends on the degree to which those physicians are really involved and the degree to which the genetic counseling is truly incorporated into the process.

Companies that offer genetic testing outside of the health-care system should be expected by regulators to show that their tests can successfully be integrated into that system in order to actually improve customers health, said Michael Murray, the director of clinical operations at Yale Universitys Center for Genomic Health.

I havent seen anything from a company thats doing this from outside of health care that demonstrates anything, he said.

Lehi, Utah-based Ancestry entered the genetic-testing market seven years ago, and with more than 15 million kits sold has become the dominant player in the ancestry DNA testing space.

In its move into health testing, it will introduce two products. Its less-expensive version, AncestryHealth Core, made its debut Tuesday. For $149, it delivers information about a handful of disease risks and health conditions, including breast cancer, as well as the original ancestry test.

A premium product, AncestryHealth Plus, which will launch early next year. It will decode the genome in far greater detail. It will cost $199, with a membership fee of $49 for six months of updates.

Georgiadis said the company didnt plan to seek FDA approval for its tests anytime soon.

Were a consumer-centric company, she said. And I truly believe that business models drive behavior. Our goal is to help people gain the preventative knowledge so that they personally can take action for their health.

See the original post:
Ancestry's DNA health screening to require a physician's order - The Union Leader

Genetic testing promises customers insights into ancestry and potential health risks. But for one Durango family, the testing also identified a new family member.

Lindsay Breed, 32, sent her saliva sample to 23andMe, a genomics and biotechnology company, two years ago to learn more about her predisposition to certain health conditions.

About a year later, in September 2018, Breed received a message through 23andMe from Jean Griffin, 62. Griffin reached out to Breed to say she thought she might be Breeds first cousin based on their DNA test results.

But the three-decades age difference between Griffin and Breed was too great. Breed and her mother, Lori Moss, looked deeper into the DNA match and family ancestry and determined Griffin must be Moss half sister.

A phone call settled the question.

I pretty much knew right away she was related to me, there were so many similarities, said Moss of Durango.

Griffin and Moss have the same height, shoe size, walk and sense of humor, she said. All qualities they inherited from their father, Clifford Carlson of Durango.

Griffin, Moss and their brother, Gregg Carlson, all clicked and still talk regularly. The three all grew up in the same area despite never knowing each other Moss and Gregg Carlson in Long Island and Griffin in Connecticut, where she still lives.

I feel like I hit the jackpot, Griffin said.

Clifford Carlson, 84, had no idea Griffin had been born as a result of a brief and casual relationship, Moss said. When Moss broke the news to her father, he was stunned, but the next day he called Moss back and asked for Griffins phone number.

Griffin and Carlson met for the first time this summer at Durango-La Plata County Airport.

It felt like an out-of-body experience, Griffin said.

Griffin knew she had been adopted and requested information about her birth parents 20 years ago through a TV show. But she didnt keep looking for information because her adoptive parents were still alive. She initially took a genetic test because she was interested in finding out more about her ancestry, but then she found her birth mother. She took the 23andMe test because she was interested in what more she could learn about her family history.

As genetic testing increases in popularity, its likely many other families are making similar discoveries all the time. At the beginning of the year, an estimated 26 million people had taken tests through four DNA testing companies, according to MIT Technology Review.

Moss advises those interested in taking a DNA test talk with family members about it.

Family members should reach out to other family members and say: I am about to do this. Are you going to be OK? Are you going to be OK if I find some hidden relatives that you didnt know about? Moss said.

If test-takers are hopeful about finding relatives, Griffin said they need to be ready for all kinds of outcomes.

It can be disappointing. ... There is a lot of not-so-good scenarios, she said.

Griffin said she approached her birth family just hoping to get to know them. She feels she got lucky.

They have been nothing but wonderful from the word go, she said.

Moss said when she first learned about Griffin she tried think about the situation from her sisters perspective.

If I was her, I would want to know my biological family, too, she said.

mshinn@durangoherald.com

Read more:
62-year-old woman meets Durango father for the first time - The Durango Herald

[He Jiankuis CRISPR babies] brought to the surface common misunderstandings even among scientists and ethicists thatreproductive usesof this genome-modifying tool have therapeutic value, will treat people with genetic disorders, will save lives, and will eradicate disease. None of those are true.

Imagine an individual or couple at high risk for creating a child with a serious genetic disease. They have the following simplified range of options:

Create a genetically related child in the time-honored fashion who will be at high risk for the genetic disease.

Create a genetically related child using CRISPR who will be at very low risk for the genetic disease.

Create no genetically related child.

The existence of option C undermines the claim that rCRISPR applications are lifesaving or curative.

Individuals have a choice in the matter of creating children at high risk of genetic disease: They can choose option C. Here is a different way of seeing the point that rCRISPR is not morally urgent because it does not involve a child whose existence, or illness, is inevitable.

Read full, original post: Using CRISPR to edit eggs, sperm, or embryos does not save lives

Read the original post:
Viewpoint: Why CRISPR embryo editing is not 'morally urgent': No one has to have a child - Genetic Literacy Project

Phenotypic screening is gaining new momentum in drug discovery with the hope that this approach will improve the success rate of drug approval.1 In this article we look at some of the latest screening tools and their applications.

This is illustrated by their recent study with Dr Ayman Zen where the team developed a high-content imaging screen using the endothelial tube formation assay, miniaturized to a 384-well plate format. Screening with an annotated chemical library of 1,280 bioactive small molecules identified a retinoid agonist, Tazarotene, that enhanced in vitro angiogenesis and wound healing in vivo. This high content screen identified an already FDA-approved small molecule that could be potentially exploited in regenerative medicine.3

Immuno-oncology: Pushing the Frontier of Discovery Through Advanced High Throughput Flow Cytometry

Immuno-oncology encompasses a number of approaches with one common thread: they harness the bodys own immune system against cancer.

Download this article to learn how advanced throughput flow cytometry overcomes these challenges to drive forward innovation in the immuno-oncology field.

Ebner is currently working in collaboration with recent Nobel-Prize winner Peter Ratcliffe, alongside scientists at Edinburgh University and MIT, to model hypoxia in glioblastoma. Hypoxia is a problem with some glioblastomas as it protects cells from radiotherapy treatment. Our aim is to use Peters expertise to help us set up an assay that mimics real tumor hypoxia. Then if we can identify small compounds that alter that hypoxic condition we can make the glioma cells more susceptible to either radiotherapy or temozolomide or some other treatment combination.

The labs main readout is high-content imaging, using fluorescent microscopy that can take many thousands of pictures. This approach utilizes different labels and harnesses software that automates the image analysis. The image analysis is set by the biologists but then it's applied across the entire screen. Its lower throughput than plate-based readout, but you get a lot more information out of the images, says Ebner. Increasingly, high content imaging is moving towards using AI and deep learning where you're trying to draw out even more information than the primary phenotype that you were looking at.

Indeed, a recent study using CRISPR-Cas9 mutagenesis showed that the proteins targeted by many cancer drugs currently in clinical development are non-essential for tumor growth, despite evidence to the contrary from previous studies using RNAi and small molecule inhibitors.4 In addition, the efficacy of the drugs tested was unaffected when CRISPR was used to knockout its assumed target suggesting that many are eliciting their anticancer activity through off-target effects.

The other benefit of CRISPR is that its extremely flexible, says Pettitt. This means you can expand the range of cell line models, for example, that you can screen in. The key reason why RNAi was such a popular technology, and now CRISPR is, is that you can basically knock out a gene by synthesizing just a short piece of RNA, he explains. CRISPR guides are very easy to synthesize, you can do it in a very high throughput setting, and you can design customized libraries to knock out every gene in the genome or a particular set of genes. As long as you can get the CRISPR machinery into your cells, it works very reliably.

The classic CRISPR (CRISPR-Cas9) system comprises a nuclease called Cas9 which you can program with a short RNA (20 nucleotides). The RNA will direct the nuclease to a certain site in the genome that matches and the nuclease will cleave the genome at that point. Repair of that double-strand break results in small insertions and deletions that result in knock out of a gene. But theres now more evolved applications of the technology emerging.

I think it's possible to be very creative with CRISPR in a way that it isnt with RNAi, says Pettitt. With RNAi you can really only shut genes off, but with CRISPR as well as making random mutations to knock out genes - you can also precisely edit genes if you provide a template region with a mutation with it. This can be incorporated into the target site for CRISPR so you can introduce the specific mutation youre interested in.

One such example is the problem with BRCA1 mutations: its important to be able to functionally classify whether these mutations are benign or pathogenic. A recent study used CRISPR to test 96.5% of all possible single-nucleotide variants (SNVs) in exons that encode functionally critical domains of BRCA1 and found over 400 non-functional missense SNVs were identified, as well as around 300 SNVs that disrupt expression. This knowledge will immediately aid clinical interpretation of BRCA1 genetic test results.5 In another study,6 Pettitt and colleagues used genome-wide CRISPR-Cas9 mutagenesis screens to identify the mutated forms of PARP that cause in vitro and in vivo PARP inhibitor resistance, and found that these mutations are also tolerated in cells with a pathogenic BRCA1 mutation resulting in a different profile of sensitivity to chemotherapy drugs compared with other types of PARP inhibitor resistance.

You couldnt screen at that level of detail using RNAi, where you design custom CRISPR that targets many different regions of the same gene and you can figure out which domains of the protein are important for your phenotype of interest, says Pettitt.

There are other evolutions of CRISPR now being developed as screens. For example, if you mutate the nuclease activity of Cas9, it still retains its ability to localize to the target site, so you can fuse Cas9 to transcriptional activators or repressors, and screen for transcriptional repression with CRISPR, as well as knock-out screens, says Pettitt. Theres also a whole range of CRISPR tools being developed that will edit bases by causing missense mutations rather than insertions or deletions, or causing methylation of DNA, or bringing in fluorescent proteins so you can visualize where the DNA sequences in the cells are. Its a measure of how flexible and useful CRISPR is in comparison to RNAi.

So will CRISPR be the one technology that everyone turns to for phenotypic screening in future? Im a firm believer that no technology answers every question, says Ebner. CRISPR is amazing, its use as a therapeutic or biologic is the stuff of science fiction. But as a tool for target identification, it comes with one important caveat. CRISPR knockout means exactly that it removes the potential protein that would otherwise be in the mix. Thats very different from a small compound inhibiting a protein that is still able to form a complex or that is just not active. Its the perfect example of a brilliant technology that is transformative, but it's not perfect. No technology is perfect.

References

1. Zheng W, Thorne N and McKew JC. Phenotypic screens as a renewed approach for drug discovery. Drug Discov. Today 2013; 18: 1067-1073.

2. Horvath P, Aulner N, Bickle M, et al. Screening out irrelevant cell-based models of disease. Nat Rev Drug Discov. 2016 Nov;15(11):751-769. doi: 10.1038/nrd.2016.175. Epub 2016 Sep 12.

3. Al Haj Zen A, Nawrot DA, Howarth A, et al. The Retinoid Agonist Tazarotene Promotes Angiogenesis and Wound Healing. Mol Ther. 2016 Oct;24(10):1745-1759. doi: 10.1038/mt.2016.153.

4.Lin et al. Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials. Science Translat Med. 2019; 11: (509). doi: 10.1126/scitranslmed.aaw8412

5.Findlay GM, Daza RM, Martin B et al. Accurate classification of BRCA1 variants with saturation genome editing. Nature. 2018 Oct; 562(7726): 217222. doi: 10.1038/s41586-018-0461-z

6.Pettitt et al. Genome-wide and high-density CRISPRCas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance. Nat Commun. 2018 May 10;9(1):1849. doi: 10.1038/s41467-018-03917-2.

The rest is here:
Phenotypic Screening Advances in Technologies and Techniques - Technology Networks

You probably know from experience that there is not as much information on small-cap companies as there is on large companies. Of course, this makes it really hard and difficult for individual investors to make proper and accurate analysis of certain small-cap companies. However, well-known and successful hedge fund managers like Jeff Ubben, George Soros and Seth Klarman hold the necessary resources and abilities to conduct an extensive stock analysis on small-cap stocks, which enable them to make millions of dollars by identifying potential winners within the small-cap galaxy of stocks. This represents the main reason why Insider Monkey takes notice of the hedge fund activity in these overlooked stocks.

CRISPR Therapeutics AG (NASDAQ:CRSP) was in 13 hedge funds' portfolios at the end of June. CRSP shareholders have witnessed a decrease in support from the world's most elite money managers of late. There were 14 hedge funds in our database with CRSP positions at the end of the previous quarter. Our calculations also showed that CRSP isn't among the 30 most popular stocks among hedge funds(view the video below). Video: Click the image to watch our video about the top 5 most popular hedge fund stocks.

5 Most Popular Stocks Among Hedge Funds

So, why do we pay attention to hedge fund sentiment before making any investment decisions? Our research has shown that hedge funds' small-cap stock picks managed to beat the market by double digits annually between 1999 and 2016, but the margin of outperformance has been declining in recent years. Nevertheless, we were still able to identify in advance a select group of hedge fund holdings that outperformed the market by 40 percentage points since May 2014 through May 30, 2019 (see the details here). We were also able to identify in advance a select group of hedge fund holdings that underperformed the market by 10 percentage points annually between 2006 and 2017. Interestingly the margin of underperformance of these stocks has been increasing in recent years. Investors who are long the market and short these stocks would have returned more than 27% annually between 2015 and 2017. We have been tracking and sharing the list of these stocks since February 2017 in our quarterly newsletter. Even if you aren't comfortable with shorting stocks, you should at least avoid initiating long positions in our short portfolio.

Oleg Nodelman EcoR1 Capital

Unlike former hedge manager, Dr. Steve Sjuggerud, who is convinced Dow will soar past 40000, our long-short investment strategy doesn't rely on bull markets to deliver double digit returns. We only rely on hedge fund buy/sell signals. We're going to take a look at the recent hedge fund action surrounding CRISPR Therapeutics AG (NASDAQ:CRSP).

Heading into the third quarter of 2019, a total of 13 of the hedge funds tracked by Insider Monkey held long positions in this stock, a change of -7% from the first quarter of 2019. By comparison, 17 hedge funds held shares or bullish call options in CRSP a year ago. With hedge funds' sentiment swirling, there exists a few noteworthy hedge fund managers who were boosting their holdings considerably (or already accumulated large positions).

No of Hedge Funds with CRSP Positions

Story continues

Among these funds, EcoR1 Capital held the most valuable stake in CRISPR Therapeutics AG (NASDAQ:CRSP), which was worth $75.8 million at the end of the second quarter. On the second spot was Cormorant Asset Management which amassed $33 million worth of shares. Moreover, Farallon Capital, Clough Capital Partners, and Valiant Capital were also bullish on CRISPR Therapeutics AG (NASDAQ:CRSP), allocating a large percentage of their portfolios to this stock.

Since CRISPR Therapeutics AG (NASDAQ:CRSP) has experienced declining sentiment from hedge fund managers, we can see that there exists a select few hedge funds that elected to cut their entire stakes in the second quarter. It's worth mentioning that Steven Boyd's Armistice Capital said goodbye to the biggest investment of the 750 funds monitored by Insider Monkey, comprising about $2.9 million in stock. Noam Gottesman's fund, GLG Partners, also said goodbye to its stock, about $1.8 million worth. These bearish behaviors are intriguing to say the least, as aggregate hedge fund interest fell by 1 funds in the second quarter.

Let's also examine hedge fund activity in other stocks similar to CRISPR Therapeutics AG (NASDAQ:CRSP). We will take a look at Box, Inc. (NYSE:BOX), MGE Energy, Inc. (NASDAQ:MGEE), Independent Bank Corp (NASDAQ:INDB), and AMN Healthcare Services Inc (NYSE:AMN). This group of stocks' market values are closest to CRSP's market value.

[table] Ticker, No of HFs with positions, Total Value of HF Positions (x1000), Change in HF Position BOX,27,395491,-5 MGEE,13,53798,4 INDB,11,16780,5 AMN,14,109685,3 Average,16.25,143939,1.75 [/table]

View table hereif you experience formatting issues.

As you can see these stocks had an average of 16.25 hedge funds with bullish positions and the average amount invested in these stocks was $144 million. That figure was $180 million in CRSP's case. Box, Inc. (NYSE:BOX) is the most popular stock in this table. On the other hand Independent Bank Corp (NASDAQ:INDB) is the least popular one with only 11 bullish hedge fund positions. CRISPR Therapeutics AG (NASDAQ:CRSP) is not the least popular stock in this group but hedge fund interest is still below average. This is a slightly negative signal and we'd rather spend our time researching stocks that hedge funds are piling on. Our calculations showed that top 20 most popular stocks among hedge funds returned 24.4% in 2019 through September 30th and outperformed the S&P 500 ETF (SPY) by 4 percentage points. Unfortunately CRSP wasn't nearly as popular as these 20 stocks (hedge fund sentiment was quite bearish); CRSP investors were disappointed as the stock returned -13% during the third quarter and underperformed the market. If you are interested in investing in large cap stocks with huge upside potential, you should check out the top 20 most popular stocks among hedge funds as many of these stocks already outperformed the market so far in 2019.

Disclosure: None. This article was originally published at Insider Monkey.

Related Content

Original post:
Is CRISPR Therapeutics AG (CRSP) Going To Burn These Hedge Funds ? - Yahoo Finance

23 Oct 2019

A multi-institutional group, including members of the Tau Consortium, unveiled a stem cell tool kit for scientists studying primary tauopathies. In the November 12 issue of Stem Cell Reports, researchers co-led by Celeste Karch ofWashington University, St. Louis, and Alison Goate and Sally Temple of Icahn School of Medicine in New York, describe a collection of fibroblasts, induced pluripotent stem cells, and neural precursor cells. The cells come from 140 skin samples, some given by donors with richly documented clinical histories who carry pathogenic MAPT mutations or risk variants. Others come from noncarrier family members, patients with a sporadic tauopathy, and cognitively normal controls. The set includes induced pluripotent stem cell lines from 31 donors and 21 CRISPR-engineered isogenic lines. The cells are available to other researchers for study.

These types of high-quality repositories are becoming increasingly important for the scientific community, Clive Svendsen of the Cedars-Sinai Medical Center in Los Angeles wrote to Alzforum.

This is the way the field is going, agreed Lawrence Golbe of CurePSP, New York. Golbes organization funds research into progressive nuclear palsy (PSP) and related disorders, and collaborates with the Tau Consortium on other projects. Enthusiastic about the resources potential, Golbe hopes CurePSP grantees will get an automatic pass to use the cells.

Choice Mutations. Cells in the new iPSC collection carry some of the most common MAPT mutations, covering a wide range of clinical and neuropathological phenotypes of frontotemporal lobe dementia (FTLD)-Tau. [Courtesy of Karch et al., 2019.]

Tauopathies have proven difficult to study in animal models, in part because unlike other neuropathologies, they seem to afflict only humans (Heuer et al., 2012). Moreover, while adult human brains express approximately equal amounts of the tau spliced isoforms 3R and 4R, rodents produce almost exclusively 4R (Trabzuni et al., 2012). This is problematic. For example, leading proposals to explain how tau mutations cause disease point to abnormalities in splicing and microtubule binding, which differ between isoforms. The models we had been focusing on were not capturing the complexity of MAPT in human cells, said first author Karch. As a result, human induced pluripotent stem cells (iPSCs) have been gaining popularity in the field. The NINDS Human Cell and Data Repository is helping meet the demand by offering iPSC lines derived from 10 patients harboring MAPT mutations.

However, Karch and her collaborators think the field could benefit from a larger and more diverse collection of human cells, including isogenic iPSC lines. To accomplish this, they collected skin samples from 140 people carrying MAPT pathogenic mutations or risk variants, non-mutation carriers, and patients with sporadic PSP or corticobasal syndrome (CBS), most with comprehensive clinical histories. Although a few cells came from the NINDS repository, most came from patients participating in longitudinal studies at the Memory and Aging Center at the University of California, San Francisco, and the Knight Alzheimer Disease Research Center at WashU. The clinical records of most of these patients include detailed neurological and neuropathological workups, as well as fluid biomarkers and neuroimaging data collected from MRI, A-PET, and tau-PET studies.

To capture a broad range of phenotypes associated with some of the most common MAPT mutations, the authors created 36 fibroblast lines and 29 iPSC lines from individuals carrying the P301L, S305I,IVS10+16, V337M, G389R, and R406W mutations, as well as from carriers of the A152T variant, which increases the risk for both PSP and CBS (image above). The latter could be particularly useful for dissecting the mechanisms that underlie the phenotypic differences between the two diseases. The researchers also obtained iPSC lines from two noncarrier family members, and two people who suffered from autopsy-confirmed sporadic PSP. In addition, they stored fibroblast lines from 12 patients with sporadic PSP, five with CBS, 10 with a mixed PSP/CBS presentation, and 69 cognitively normal controls.

Biopsies are available for 27 of the 31 patients whose cells were used to generate iPSCs, and autopsy data for seven, including the two cases of sporadic PSP.

Importantly, the researchers edited 21 iPSC lines using CRISPR/Cas 9. They corrected cells with these mutations: MAPT IVS10+16,P301L, S305I, R406W, and V337M. Conversely, they inserted into control iPSCs these mutations: R5H, P301L,G389R, S305I, or S305S.

The authors also created a stem cell line carrying MAPT P301S,a mutation commonly overexpressed in tauopathy mouse models but not present in the available donors, by editing the P301L line. Isogenic lines are so powerful, particularly in these diseases which are so variable in their onset and progression, even within the same family, said Karch. Gnter Hglinger and Tabea Strauss at the German Center for Neurodegenerative Disease (DZNE) in Munich agreed. Having a pool of cell lines with different disease-linked mutations and risk variants from several individuals and their isogenic control cells is an excellent resource for the research community to enlighten disease mechanisms, they wrote (full comment below).

Several of the reported lines have already starred in recent studies of tauopathy mechanisms and candidate therapies (e.g., Sep 2019 conference news; Nakamura et al., 2019; Hernandez et al., 2019; Silva et al., 2019).

Karch and colleagues have partially differentiated some of the iPSCs and stored them as neural progenitor cells (NPCs), so that researchers can relatively easily thaw, expand, and differentiate them into neurons. These NPCs have proved useful for large-scale functional-genomics studies, proteomics, and genetic modifier screens (e.g., Cheng et al., 2017; Boselli et al., 2017;Tian et al., 2019).

In addition, the authors inserted a neurogenin-2 transgene into two healthy controls and two MAPT mutant stem cells, P301L and R406W. Neurogenin-2 enables low-cost, large-scale differentiation of stem cells into homogenous excitatory neurons. These transgenic cells are particularly useful for high-throughput drug screens (Wang et al., 2017; Sohn et al., 2019).

Researchers can request all the reported cells online at http://neuralsci.org/tau. They must provide a summary of experimental plans, an institutional material transfer agreement, and a nominal fee to cover maintenance and distribution costs. Karch said the process resembles that of the Coriell Institute and the NINDS repository. Our goal is to share with as few hurdles as possible, she said.

While the authors are still reprogramming fibroblasts they have already collected, they also plan to add more causative mutations, generate more isogenic lines, and obtain more cells from members of the same families to help shed light on phenotypic variability. In addition, Karch said, she hopes repository users will resubmit lines with new modifications they generate.

Jeffrey Rothstein, Johns Hopkins University, Baltimore, welcomed the new resource. I think it is great they have assembled this collection, he said. Rothstein founded and co-directs the Answer ALS research project, which has amassed 600 iPSC lines from controls and patients with amyotrophic lateral sclerosis (ALS).

Rothstein suggested the tauopathy collection may want to prioritize adding cells from donors with the most common form of disease, that is, sporadic. His group aims to generate 1,000 iPSC lines, with a large fraction representing sporadic diseasealso the most common form of ALSto identify the most prevalent disease subtypes. One strategy that has helped his group build their collection, he said, is using peripheral blood mononuclear cells instead of fibroblasts to create iPSCs. More donors are willing to donate blood than have a piece of skin punched out. In addition, iPSCs derived from blood cells are genetically more stable, he noted.

Rothstein emphasized the importance of assembling a large collection of healthy controls. Although isogenic controls are of great value, he cautioned they can be subject to artifacts. One problem is that the cell population can change due to selective pressures during CRISPR editing (Budde et al., 2017). To address this, Karch and colleagues are collecting not only modified iPSC clones, but also control clones that have gone through the editing pipeline but remain unmodified.

Stem-cell users studying tauopathies face another challenge: iPSC-derived neurons express primarily the fetal isoform of tau, 3R0N. However, citing a study that shows three-dimensional neuronal cultures switch to the adult profile relatively quickly (Miguel et al., 2019), Hglinger and Strauss wrote, [It] allows us to be optimistic that current challenges of this model system can be overcome in the future.Marina Chicurel

Read more:
Introducing: iPSC Collection from Tauopathy Patients - Alzforum

A gene therapy for a rare blood disorder has shown what the manufacturer calls the first evidence of long-term improvement associated with the disease.

New York-based Rocket Pharmaceuticals said Thursday that it had presented long-term follow-up data from the Phase I/II study of RP-L102, its gene therapy for Fanconi anemia, at the annual congress of the European Society of Cell and Gene Therapy in Barcelona, Spain. The company said it represented the first evidence of long-term improvement and stabilization in blood counts and durable mosaicism among patients who received the therapy without the use of the conditioning regimens normally used for allogeneic stem cell transplants, which the company calls Process A.

Shares of Rocket were up slightly on the Nasdaq following the news. RP-L102 is a lentiviral vector-based gene therapy. Most other gene therapies in development, and both of the currently marketed ones Spark Therapeutics Luxturna (voretigene neparvovec-rzyl) and Novartis Zolgensma (onasemnogene abeparvovec-xioi) are adeno-associated viral vector-based.

According to the data, representing four of nine patients, there were improved blood counts and long-term bone marrow mitomycin C (MMC) resistance, thereby indicating durable phenotypic correction. The data met or exceeded a 10 percent threshold that the company said the Food and Drug Administration and European Medicines Agency had agreed to for its upcoming Phase II registration study, for which it plans to start enrolling patients by the end of the year.

FA is a rare, genetic bone marrow failure disorder, half of whose patients are diagnosed before the age of 10, while about 10 percent of patients are diagnosed as adults, according to the National Organization for Rare Disorders. It is often associated with progressive deficiency of production of red and white blood cells and platelets in the bone marrow and can eventually lead to certain solid and liquid tumor cancers. It occurs in 1-in-136,000 births and is more common among Ashkenazi Jews, Spanish Roma and black South Africans.

These results indicate the feasibility of engraftment in FA patients using autologous, gene corrected [hematopoietic stem cells] in the absence of any conditioning regimen, said Dr. Juan Bueren, scientific director of the FA gene therapy program at Spains Center for Energy, Environmental and Technological Research, in a statement. This indicates the potential of this therapeutic approach as a definitive hematologic treatment, while avoiding the burdensome side effects associated with allogeneic transplant, including the risk of post-transplant mortality and a substantially higher risk of head and neck cancer.

Photo: virusowy, Getty Images

Read more here:
Rocket's gene therapy shows long-term efficacy in rare blood disorder - MedCity News

The National Institutes of Health and the Bill and Melinda Gates Foundation will together invest at least $200 million over the next four years to develop gene-based cures for sickle cell disease and HIV with an attribute even rarer in the world of genetic medicine than efficacy, the groups announced on Wednesday: The cures, they vowed, will be affordable and available in the resource-poor countries hit hardest by the two diseases, particularly in Africa.

The effort reflects growing concerns that scientific advances in genetic medicine, both traditional gene therapies and genome-editing approaches such as CRISPR, are and will continue to be prohibitively expensive and therefore beyond the reach of the vast majority of patients. Spark Therapeutics Luxturna, a gene therapy for a rare form of blindness, costs $425,000 per eye, for instance, and genetically engineered T cells (CAR-Ts) to treat some blood cancers cost about the same.

With CRISPR-based treatments already being tested in clinical trials for sickle cell disease, the blood disorder beta thalassemia, and another form of blindness, and with additional CRISPR treatments in development, scientists, ethicists, and health policy experts have grown increasingly concerned that the divide between haves and have-nots will grow ever-wider.

advertisement

Gene-based treatments are largely inaccessible to most of the world by virtue of the complexity and cost of treatment requirements, which currently limit their administration to hospitals in wealthy countries, the NIH said in a statement. To help right that, its collaboration with the Gates Foundation aims to develop curative therapies that can be delivered safely, effectively and affordably in low-resource settings.

Scientists whose research focuses on gene-based cures welcomed the infusion of funding and the recognition that genetic cures are on track to be unaffordable to the majority of patients. But they noted one irony. The most effective sickle cell drug, hydroxyurea, has hardly even been studied in sub-Saharan Africa, let alone made widely available. Yet a 2019 study found that giving children the drug cut their death rate by two-thirds and halved the pain crises that are common in sickle cell disease, caused by misshapen red blood cells that cannot flow through blood vessels.

The NIH-Gates collaboration is tremendously exciting and has the potential to have a great impact on sickle cell disease in sub-Saharan Africa, said Dr. Vijay Sankaran of the Dana-Farber/Boston Childrens Cancer and Blood Disorders Center, who has done pioneering research on genetic cures for the disease. But my hesitation is that even the inexpensive therapies we have today, such as hydroxyurea, are largely unavailable there. The question is, how do we best approach this disease, with therapies that are working today or with genetic therapies that might work?

The same concerns surround HIV. Very inexpensive less than $100 per year in the U.S. antiretroviral drugs can keep the virus in check, but only 67% of HIV-positive adults and 62% of HIV-positive in children in east and southern Africa are estimated to be on antiretroviral treatment.

The new collaboration aims to move gene-based cures into clinical trials in the U.S. and countries in sub-Saharan Africa within the next seven to 10 years, and to eventually make such treatments available in areas hardest hit by sickle cell disease and HIV/AIDS. The idea is to focus on access, scalability, and affordability to make sure everybody, everywhere has the opportunity to be cured, not just those in high-income countries, NIH Director Francis Collins said in a statement. We aim to go big or go home. But the challenge is enormous, he told reporters on Wednesday: Im not going to lie. This is a bold goal.

An estimated 95% of the 38 million people with HIV live in the developing world, with 67% in sub-Saharan Africa. Up to 90% of children with sickle cell disease in low-income countries die before they are 5 years old. In the U.S., the life expectancy for people with sickle cell disease is in the low 40s.

The NIH and the Gates Foundation will fund research to identify potential gene-based cures for sickle cell and HIV, and also work with groups in Africa to test those cures in clinical trials.

The science of genetic cures for both diseases is within reach, experts say. CRISPR Therapeutics and Vertex (VRTX) are already running a clinical trial for sickle cell disease, using the CRISPR genome editor to do an end-run around the disease-causing mutation in the hemoglobin gene: The therapy releases the brake on red blood cells production of fetal hemoglobin, whose production shuts off in infancy but which does not have the sickling damage of adult hemoglobin.

Developing effective, safe genetic cures for sickle cell and HIV would be only a first step, however. As currently conceived, such therapies require advanced medical facilities to draw blood from patients, alter their cells genomes in a lab, give the patients chemotherapy to kill diseased blood-making cells, and then perform whats essentially a bone marrow transplant, followed by monitoring patients in a hospital for days to prevent infection and provide intensive medical support, said Dr. Dan Bauer, a sickle cell expert at Boston Childrens.

He called the NIH-Gates effort terrific, but cautioned that delivering advanced gene therapies requires tremendous effort, extended hospitalization, and large supplies of blood products. All of those requirements mean that even if a CRISPR-based cure for sickle cell disease or HIV were provided at cost, there will still be barriers to access.

Recognizing that, Collins said, a genetic cure would have to be given directly into patients (in vivo), presumably through an infusion, rather than by treating blood or other cells removed from patients and genetically transformed in a lab (ex vivo). That could avoid the resources needed for and the complications that can occur with ex vivo therapies, said Sankaran, who has discussed the approach with Gates officials.

This story has been updated with additional comments.

Continue reading here:
NIH, Gates Foundation aim to bring genetic cures to the poor - STAT

Assessing the challenges

As part of the CRA analysis, the team reached out to a range of industry stakeholders including experts in drug development and commercialisation, academic researchers, investors and payers for insights about emerging annuity pricing models and the challenges they can present.

Research also included a global review of launch dates and regulatory information related to several cell and gene therapies.

Input from industry insiders and experts identified a range of concerns associated with annuity payment models, including a potentially significant impact on cost of capital and company valuations, costs and burden of long-term patient monitoring, the need to make reimbursement decisions based on very limited long-term clinical data, and the need to consider entirely new business models and forecasting strategies based on extended payment schedules.

Despite the challenges, some cell and gene therapy companies have already launched products based on annuity pricing models. GlaxoSmithKline (GSK) launched its gene therapy STRIMVELIS, a one dose treatment for severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID), in Europe in 2016 with an outcomes-based annuity pricing model.

Under the terms of this model, payments to GSK by payers are spread out over a pre-determined timeline for each treated patient. The model confirms that GSK must return a portion of the reimbursement to the Italian Medicines Agency if the drug does not demonstrate a sufficient level of efficacy based on pre-determined outcomes measures.

In their assessment, based on the mutually determined outcomes measures, GSK projected that aboutone in six treatments on average might need to be partially refunded.

The financial impact of annuity payment models

Annuity models require manufacturers to consider several factors that can increase their own operational costs as well as the cost of capital. With annuity models, the risk that a payer might not be a viable long-term business entity or may contest a payment schedule could mean a potentially devastating disruption in revenue fora manufacturer.

While the use of insurer-backed annuity payments as collateral for secured loans can help mitigate this risk, in considering this option manufacturers need to carefully consider multiple factors, including trends in interest rates and the duration of the annuity contract, the cost of capital based on a lenders fees, operational repayment milestones and the expected costs of goods.

Both manufacturers and payers must also complete risk assessments based on available data, which will often be more limited than data used in traditional outcomes and risk assessments.

Banks and other lenders will also likely complete their own due diligence in evaluating many factors, including levels of payer interest, patient outcomes measures and the terms of annuity contracts to determine their own acceptable level of risk, often with limited relevant experience. In many cases, lenders will also require drug developers to provide audited cash flow statements.

Optimal strategies for mitigating risk

As progress in the development of cell and gene therapies continues to advance, payers andhealth systems can anticipate the introduction of many new high-priced drugs in the near future.

While annuity pricing models are already a widely considered option to address the unique reimbursement issues associated with cell and gene therapies, developing and implementing these plans successfully will require careful analysis and successful efforts in building consensus among all stakeholders.

The risks may be especially acute among biotechnology companies with only one drug on the market. Manufacturers will need to bring together the full range of resources and expertise necessary to assess the impact these models will have on capacity, cash flow and long-term business planning.

To achieve this goal, drug developers will need to reach out to a broad set of stakeholders for guidance and expertise.

They may need to work closely with finance providers such as banks and other lenders and seek collaborations with consultants in market access early in a development programme to begin what is likely to be a long-term initiative in planning and programme execution.

It is likely that there will not be one simple solution. Effective approaches in reimbursement of cell and gene therapies may need to include elements from several potential models including, but not limited to, annuity-based models.

But the progress in research means that development of innovative pricing models that optimise benefits and balance risks for manufacturers, payers and health systems will become increasingly time sensitive as more paradigm-changing cell and gene therapies advance toward commercialisation.

The views expressed herein are the authors and not those of Charles River Associates (CRA) or any of the organisations with which the author is affiliated.

More here:
Assessing the risks in annuity pricing models - PMLiVE

October 25, 2019

Researchers working to find a cure for malignant mesothelioma are acutely aware of the need for speed: the disease is always considered fatal, and more people are diagnosed with and die of the condition every day. Still, there is a process that must be followed: theories need to be tested in the laboratory before people, and this slows everything down. Recently, researchers at the University of Pennsylvania had the opportunity to see the human results of a protocol that had shown promise with lab animals but is not yet ready for patient testing. They reported a significant positive outcome.

Previous animal research had combined radiotherapy with immune-gene therapy in the treatment of mice with malignant pleural mesothelioma, and had revealed both disease regression and what is called an abscopal effect the combination not only affected tumors that were targeted by radiation but also those that were outside of the range of the therapy.

The researchers from thePerelman School of Medicine at the University of Pennsylvaniadid not intend to test the effect on humans, but ended up doing so with a 67-year-old male patient with malignant pleural mesothelioma who signed on for a clinical trial of immuno-gene therapy. Though his tumor responded positively he needed to stop the treatment due to complications from his tumor for which he was given palliative radiation therapy followed by a standard course of chemotherapy.

Two months after having completed the course of palliative radiotherapy, the man had a CT scan of his chest that revealed that the targeted mesothelioma tumor had shrunk. Remarkably, the treatment had also shrunk tumors that were outside of the irradiated field. This is the first report of a patient having an abscopal effect following radiotherapy and immune-gene therapy. Writing of his results, lead researcher Andrew R. Barsky said, The patients response to immuno-gene therapy, palliative radiotherapy and subsequent chemotherapy, both in-field and out-of-field, was dramatic, and notably more pronounced than what is generally achievable for even well-responding malignant pleural mesothelioma patients In fact, his exaggerated response was far greater than would be expected based upon the volume of disease irradiated and radiation dose employed. The researchers plan to pursue further study of this dynamic.

If you or someone you love has been diagnosed with malignant mesothelioma, positive outcomes like these offer reason for hope. For more information on treatment protocols available to you, contact the Patient Advocates at Mesothelioma.net at1-800-692-8608.

Learn more about and contact Terri

See the original post:
Oncology Team Reports Promising Results From Combining Immuno-gene Therapy and Radiotherapy - Mesothelioma.net Blog

Let's play a game of word association. I'll go first.

Cell Therapy

What words spring to mind? CRISPR? Medicine? Genetic disorders? Cancer? Gene therapy?

What about green tea? Unlikely, I imagine.

But in a new study published today in Science Advances, researchers from East China Normal University have created an elegant system for activating genetically edited cells using green tea.1Realizing the promise of cell therapiesEngineered cell therapies, deemed the "next frontier" in modern medicine, contain specific cellular material that triggers a desired effect in vitro or in vivo. Such therapies are in development in laboratories across the globe for an array of different conditions, including acute myocardial infarction (heart attack), brain cancer, breast cancer, diabetes and liver diseases. They offer a novel avenue of therapeutics for patients suffering from diseases for which treatment options are limited.For their efficacious and safe use in the clinic, scientists need to be able to regulate the activity of these cells in vivo. Essentially, they require a "remote control". This has proven a major barrier for the delivery of cell therapies to patients. Initial work in this field has adopted antibiotics such as doxycycline or tetracycline as remote-control triggers for gene expression in the cells. However, regular use of antibiotics may result in antibiotic resistance and other adverse side effects.So, what alternatives exist?Haifeng Ye, Professor at East China Normal University, says "Ideal trigger molecules for clinical biomedical applications would be natural, non-toxic, highly soluble, inexpensive, and perhaps even beneficial to health."Previous studies have reported that remote control switches can be activated through the use of food or cosmetic preservatives, vanillic acid, benzoate and phloretin for example. These molecules do not naturally occur in food however, and the safety implications of their long-term use is not well known.A green solution?Nothing beats a good cup of tea. It is the second most popular beverage on the planet (following water) and can be found in the household cupboards of 80% of Americans. Tea is available in a variety of forms, including but not limited to black tea, oolong tea, white tea and green tea. A plethora of research studies have documented the numerous health benefits of green tea consumption, including anticarcinogenic, anti-inflammatory, antimicrobial, and antioxidant effects.The components of green tea most heavily researched with regards to health are the polyphenols, of which the most pertinent are flavonoids, and the most pertinent flavonoids are the catechins.2Post green-tea consumption, the tea catechins and phenolic acids undergo metabolic processing to form the antioxidant protocatechuic acid (PCA). In their latest study, Ye and team have utilized this antioxidant as a "remote control" for activating gene switches in cells. "PCA is a major tea catechin compound produced by humans following green tea consumption that has powerful antioxidant activity. Therefore, in this study, we showed the use of protocatechuic acid (we call it PCA), a metabolite after tea drinking, as a trigger molecule," Ye told Technology Networks.PCA-inducible gene switchesIn the study, the scientists engineered PCA-inducible gene switches in mammalian cells. Initially, they explored the potential for using PCA to monitor cell-based long-term therapies in vivo by integrating the genetic switch into HEK-293 cells and found that the cell line demonstrated reversible and tunable induction kinetics, which the authors regard as "excellent switching performance". This was characterized by negligible basal expression and nonsaturating increases in the transgene output over the course of a 15-day trial.Next, they microencapsulated and implanted the HEK cells into mice. Ye tells us, "The alginate-poly (L-lysine)-alginate-based encapsulation technology was used in our study for cell therapy. This clinically validated implant technology enables the free diffusion of metabolites, nutrients and proteins of lower molecular weights (<72 kDa) across the biocompatible capsule membrane while shielding their cellular content from physical contact with the hosts immune system. The implant technology has been successfully validated in human clinical trials and the performance of the material is continuously improved for clinical applications."The researchers found that, regardless of delivery method (intraperitoneal, oral intake from water, or oral intake from concentrated green tea), PCA could control the secretion of a reporter protein, SEAP, in a dose-dependent manner.Making CRISPR more crisp?CRISPR gene-editing shows promise in revolutionizing personalized medicine. A notable key issue with CRISPR, however, is the "off target" effects that limit its specificity. In this study, the scientists used the PCA-responsive cells to perform more targeted CRISPR gene editing: "By applying newly-designed fusion-protein-based PCA-controlled gene switches to Pol III promoters, we created trigger-inducible expression systems for gRNAs to program PCA-mediated CRISPR/Cas9-activity," says Ye.Exploring diabetes treatment with PCA-induced cell therapyYe and colleagues next tested the potential of the PCA remote control system for treating experimental diabetes using a mouse model. Using the switch, they engineered two different cell lines: one that enabled PCA-inducible expression of the reporter protein SEAP and insulin, and the other producing a short variant of human glucagon-like peptide 1 and SEAP. Implantation of these cells into mouse models of type 1 diabetes and type 2 diabetes mellitus resulted in restored homeostatic fasting blood glucose concentrations and glucose tolerance upon PCA injection.Recognizing that the translation of research findings from mouse models to humans in the clinic can be problematic, the scientists then decided to explore the PCA remote control switch efficacy in non-human primate models of diabetes. In parallel to the treatment efficacy observed in the type 2 diabetic mice, daily oral administration of PCA rapidly increased the expression of glucagon-like peptide 1 and restored glucose homeostasis in diabetic monkeys.In terms of safety, blood biochemical analyses related to inflammatory responses found that white blood cell count, lymphocytes, monocytes, eosinophils, and basophils, did not increase at any point during the treatment when compared with pre-treatment.The study findings certainly excite the authors, "Although there have not yet been preclinical studies for the application of engineered cellbased therapies in humans, this first-in-monkey study demonstrates the feasibility of safely and successfully scaling up a treatment strategy by controlling microencapsulated engineered cells to release therapeutic outputs from animals such as mice to larger NHPs. Therefore, this study substantiates the medical utility of concepts developed in synthetic biology," they note in the discussion of the paper.How much tea is too much tea?Hypothetically, if this therapy was to reach the clinic, I ponder over the possibility of an individual consuming "too much" green tea, and how this might impact the therapy. Ye is quick to inform me that this would not be an issue, "Only custom prepared concentrated green tea can activated the implanted designer cells. The normal green tea drinks cannot activate the implanted cells because of low concentration," he says.The future looks greenThe study is comprehensive, assessing the PCA "switch" in a variety of cell lines and mammalian models with a variety of control measures in place.Thus, in which direction will this research go next? I ask Ye, who tells me, " We will next focus on solving the following limitations:(1) The PCAON-switch was stably integrated into [the] genome by a "Sleeping Beauty" transposon system. Due to a random integration, unwanted insertional mutagenesis might occur. We will next consider using gene editing tools, such as CRISPR, to enable facile and permanent integration of the switch into the targeted genomic sequences in human cells without insertional mutagenesis;(2) The chassis of the HEK-293 cells are easily handled, transfected, and compatible to the PCAON-switch. For translational applications, they must also be safe (no side effects) in humans. Hence, we will test the therapeutic efficiency of the PCAON-switch in autologous parental cells from patients own mesenchymal stem cells, which may provide immunocompatible and noncarcinogenic autologous or allogeneic cell sources;(3) The lifespan of the designer cells inside the alginate microcapsules is an imperative issue. To realize long-term cell therapy, we will further improve the encapsulation technology."Haifeng Ye, Professor at East China Normal University, was speaking with Molly Campbell, Science Writer, Technology Networks.References:1. A green teatriggered genetic control system for treating diabetes in mice and monkeys," by J. Yin; L. Yang; K. Dong; J. Jiang; S. Xue; Y. Xu; X. Wang; H. Ye at East China Normal University in Shanghai, China; L. Mou; Y. Lu at First Affiliated Hospital of Shenzhen University in Shenzhen, China.2. Reygaert. 2018. Green Tea Catechins: Their Use in Treating and Preventing Infectious Diseases. Biomed Research International. doi: 10.1155/2018/9105261.

Go here to see the original:
Green Tea Acts as a "Remote Control" To Switch on Cell Therapy - Technology Networks