Archive for April, 2024

Jansen Jones wasnt using her hands or legs.

She lacked muscle tone and was too weak to bear weight using her extremities.

The baby could lift and move her head, but she didnt seem as strong as a 5-month-old should be, her mother believed.

"She is my third child," Suzanne Jones said, which means she's witnessed developmental milestones twice previously.

Doctors at Childrens Healthcare of Atlanta diagnosed Jansen with a nonspecific, global developmental delay.

We were just told, She's behind. No big deal. Do some physical therapy, Jones said.

But a lot of babies seem really strong, and it was clear to Jones that Jansen was not.She would curl up in a sort of ball, and sat looking sweet and happy, but did not engage with her environment.

A neurologist said a muscle biopsy might explain the deficiency, but there are false positives with muscle biopsies.

"That is invasive and leaves a scar and scared us," Jones said. "You know, you're basically cutting on her arm or leg."

When Jansen didn't babble as expected, they started speech therapy. Then, they added occupational therapy.

"We just did hours and hours of therapies nonstop for years," Jones said.

A neuro-psychological exam led doctors to say Jansen was intellectually disabled.

This happened about the same time as rare, fleeting seizures caused Jansen to space out for a second or two.

An electroencephalogram (EEG) test confirmed abnormal electrical activity in her brain.

"Well, they just said she has epilepsy," Jones said.

But Jones said the family continually witnessed symptoms that suggested that Jansen was struggling in different ways.

The idea of genetic testing came up by the time Jansen was 3 years old.

"In my opinion, if it's genetics, that's the underlying cause of everything and so that should show us what is going on," Jones said.

Jones doctors described the 46 chromosomes in the body as chapters in a book. Whole exome sequencing was like scanning the book to see whether any chapters were missing or duplicated.

For example,the characteristic features and developmental problems of a person with Down Syndrome is caused by an extra chromosome 21.

Think of that as Chapter 21.

But after having Jansen's whole exome sequenced, they still had no solid answers.

"And so we got results back when she was 3 and it did not show us what was going on," Jones said.

All the Joneses could do was treat Jansen's symptoms, which included behavior problems.

Despite managing Jansen through applied behavior therapy and medication, Jansen acted out and shecouldn't control it. Nightmares made her want to sleep in bed with her parents.

"It's not clear to me why the whole exome sequencing didn't catch it," Jones said. But it's not an infallible test.

An exome is a collection of 180,000 exons responsible for protein coding, but the human exome only comprises about 1% of the human genome.

Now, whole genome sequencing is available.

"And that is what ended up catching it," Jones said.

Jansen was diagnosed just before her 11th birthday with a disorder caused by a single gene mutation: SYNGAP1.

"This mutation was discovered only a year before Jansen was born."

Jansen's frustration stemmed from an inability to reason and communicate.

She turned 13 in October 2023.

"It's not easy," Jones said. "They have a SYNGAP snap. Sometimes their brain just [goes] haywire. And you can't you can't reason with somebody who can't reason. So behaviors can be really difficult."

"Compared to other single-gene mutations that cause epilepsy, SYNGAP1 children have a lot of problems with behavior," Jones said. "And luckily with that being a spectrum, my child has those issues, but it's not constant; it's not as prevalent."

If you have a rare disease, there is an 80% chance that its genetic. That doesnt mean the cause has been identified yet.

Karen Grinzaid with Emory University School of Medicine said she believes everyone planning a family should conduct genetic testing.

"The reason is there are genetic diseases that can happen that haven't shown up in your family yet," she said.

We all carry a number of recessive genes, but we don't know what those genes are unless either we have an affected child, or we do genetic testing.

But a whole genome test like Jansens might make would-be parents more nervous than is necessary.

"When you do broader testing like that, it may turn up problems where it's not clear what the implications are," Grinzaid said. "So, I just can't overemphasize the importance of genetic counseling to help people through this journey."

Suzanne Jones said even though her daughters diagnosis hasnt changed her daughters developmental issues, the genomic sequencing was worth it.

"It's an answer," she said. "We can finally say we understand what all these different symptoms are caused by."

And that, Jones said, makes it a lot less scary to be a parent.

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80% of rare diseases are genetic. That's why whole genome sequencing can help with diagnoses - GPB News

Sponsored by Embark

Adam Christman, DVM, MBA: We're chatting so much in this day and age about customized care, individualized care, and what does that mean now that we have in Embarks DNA testing kit available? What does that look like to the pet parent's perspective and to the veterinarian that we have now, like a customizable care program?

Jenna Dockweiler, MS DVM, DACT, CCRT, CVAT: So I think we've kind of evolved as a profession over time. You know, initially we practice medicine, and then we practice species-based care, as in cats are not small dogs. Then we started to practice breed-based medicine. Perhaps these things are more breed-associated than others. This is really the next frontier, so personalized medicine.

In addition to MDR1, there are other things that are on our genetic test that could offer some personalized care. One that comes to mind for me is a variant in the POMC gene that interferes with satiety. So if you have a fat lab who comes in, which we see every day, you're doing thyroid testing, the owner swears up and down, you know, they're not feeding the dog anything extra, but he's always hungry.

So this POMC gene really can interfere with satiety and just give a reason for why that pet might be constantly hungry and potentially, maybe overweight. I find it's very helpful to point to something to say, "Hey, this is why your dog maybe has trouble with feeling full." So he's not actually starving, you know? So we can follow this weight management plan.

Adam Christman, DVM, MBA: Yeah, I love that.

Lindsey Kock, DVM: That is one of my favorite studies because if you dig into it, they used assistant dogs in that study and they found that dogs who were really trainable had that POMC mutation, but it makes sense, right? They were food motivated. And so, a lot of dogs that end up in assistance programs tend to be food motivated, tend to be easier to train. It tells us about satiety, and it tells us, you know, things that we wanna know about weight management.

But the other thing it tells us is making some training recommendations, right? So a dog who has the POMC variant might be more likely to be really trainable with food. But we may be able to talk to pet owners who have dogs that don't have that mutation about some other tactics that they can use for training too when they might be having a tough time at home. So it's interesting how when we learn about genetics, sometimes there's the second layer of other ways that that we can apply that information in practice, which is really cool.

Adam Christman, DVM, MBA: There's a practice that has this wonderful thought philosophy that says everyone is a VIP and it's very individualized for the pet and pet parent. And what they do is for every dog whether it be a rescue dog, from a breeder, a puppy, it's included in the initial visit that they already have the Embark DNA test there. What are your thoughts on that?

Jenna Dockweiler, MS DVM, DACT, CCRT, CVAT: I think that's a great way to, again, build trust between the client and the practice because everybody feels like the plan is really made together. This is individual for my dog specifically. It's not just the breed or the presumed breed mix. This is my dog so I think that's a great tactic.

Adam Christman, DVM, MBA: Yeah and because they get so excited when they see right and I, to your point, where we're just talking about the human animal bond and we want to bond with our clients in the exam room like that. You want to be excited for them and so having that discussion about genetic testing and being a proactive approach to care I think is so powerful. What are your thoughts on that?

Lindsey Kock, DVM: One thing I think about, too, is we tend to see trends carrying over from human medicine. So I think about how people's animals are parts of the family, right? And they expect them to get the same sort of personalized treatment that a family member may have gotten or that they may have gotten. And so I think, as human medicine becomes more personalized, and we start to use genomic testing in different areas of human medicine, it's important to understand how that is going to impact clients' expectation of us as veterinarians too.

For me, this plays into expectations for personalized care based on things that those clients may seek out if they've done a consumer DNA test. If they've looked at their microbiome, if someone in their family has gone through treatment for cancer and they've done personalized care. So I think the more we start thinking about this type of technology and how we can apply it, I think it's fair to think about the big picture too and client expectations.

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Personalized care and treatment plans - DVM 360

Aim to demonstrate whole genome sequencing can replace the standard diagnostic cascade, for potentially faster diagnosis and lower costs

SECAUCUS, N.J., April 2, 2024 /PRNewswire/ --Quest Diagnostics (NYSE: DGX), a leader in diagnostic information services, and Broad Clinical Labs, the world expert in whole genome sequencing (WGS), today announced a research collaboration designed to demonstrate the clinical value of WGS as a first-line genetic test for postnatal diagnosis of developmental delay disorders.

The parties expect to demonstrate that WGS can provide insightsfrom a single blood testthat are at least as clinically accurate as the multiple conventional tests providers typically use to diagnose a patient.

"We are delighted to bring the experience and expertise of Broad Clinical Labs to this innovative collaboration with Quest. We believe that the genome is a platform upon which many research, screening, and diagnostic tests can be built resulting in benefits for patients and providers alike," said Niall J. Lennon, Ph.D., Chief Scientific Officer of Broad Clinical Labs and Senior Director of Genomics at the Broad Institute of MIT and Harvard.

"WGS has the power to enable a new diagnostic paradigm, where a physician can access genetic insights faster on the patient's diagnostic journey--without multiple doctor visits and lab tests," said Mark Gardner, Senior Vice President, Molecular Genomics and Oncology at Quest Diagnostics. "Broad is the leader in genomic science and Quest is the leader in laboratory testing at scale, so together we have the right combination of skills to explore the potential of WGS to replace the conventional model."

"This research initiative by Broad and Quest involves both phenotypic and genotypic data sharing in an effort to further enhance interpretation of genomic tests and the understanding of development delay," said Heidi Rehm, Ph.D., FACMG, Medical Director of Broad Clinical Labs, and Chief Genomics Officer of Massachusetts General Hospital. "This type of collaboration between commercial laboratories and research institutions is vital to advance the field of genetic testing and increase utility and economic value."

Creating a New Testing Model to Simplify and Speed Diagnosis

Nearly 2% of children manifest intellectual disability. Yet, it can take weeks, months, or even years to identify the underlying cause of intellectual disability or developmental delay, causing a "diagnostic odyssey" for patients and their families. Identification of an underlying diagnosis can lead to changes in management that "will influence mortality, morbidity, and reduce the burden on patients and families searching for answers," according to the American College of Medical Genetics and Genomics.

While the ACMG recommends WGS for first-line genetic testing for intellectual disability and developmental delay, some providers continue to follow prior guidelines that recommend chromosomal microarray (CMA) as a first-line test. CMA is less informative than WGS, and patients whose findings are negative by CMA can require additional rounds of testing, such as with narrow gene tests or genetic panels or exome sequencing, until a cause is found.

"Now that the $100 genome is moving closer to reality, it's time to reconsider the way genetic testing is utilized and reimbursed and, ultimately, end the diagnostic odyssey for children and their families," Mr. Gardner added.

Through the collaboration, Quest will provide de-identified data, including phenotypic (a person's observable traits), and blood, saliva, and buccal swab specimens it has tested for developmental delays using CMA and other tests. Broad will then perform WGS on the de-identified specimens to determine concordance between the methods.

The collaboration will also explore the potential of WGS to provide answers for Fragile X syndrome. Unlike CMA or exome sequencing, WGS can rule out Fragile X as a cause of developmental delay and signal the need for additional confirmatory testing in those whose results suggest it as a possible cause of developmental delay.

Broad Clinical Laboratories, previously known as Clinical research sequencing platform, was founded in 2013 as a non-profit subsidiary of Broad Institute of MIT and Harvard to accelerate the genomics community and the world toward a better understanding, diagnosis, and treatment of disease by pursuing projects, developing products, and driving adoption of cutting edge -omics technologies and novel molecular assays.

Broad Clinical Labs is a leader in human whole genome sequencing, having sequenced over 600,000 genomes in service of its mission to accelerate the understanding and diagnosis of human disease. http://www.broadclinicallabs.org

About Quest DiagnosticsQuest Diagnostics works across the healthcare ecosystem to create a healthier world, one life at a time. We provide diagnostic insights from the results of our laboratory testing to empower people, physicians and organizations to take action to improve health outcomes. Derived from one of the world's largest databases of deidentified clinical lab results, Quest's diagnostic insights reveal new avenues to identify and treat disease, inspire healthy behaviors and improve healthcare management. Quest Diagnostics annually serves one in three adult Americans and half the physicians and hospitals in the United States, and our nearly 50,000 employees understand that, in the right hands and with the right context, our diagnostic insights can inspire actions that transform lives and create a healthier world. http://www.QuestDiagnostics.com.

SOURCE Quest Diagnostics

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Quest Diagnostics and Broad Clinical Labs to Evaluate Whole Genome Sequencing as First-Line Genetic Test for ... - PR Newswire

Patients in England and Wales who have recently had an ischaemic stroke or transient ischaemic attack could be offered genetic testing to help inform their treatment, following backing from the National Institute for Health and Care Excellence (NICE).

The agency has launched a second consultation on recommendations that clinicians should offer CYP2C19 genotype testing when considering treatment with clopidogrel, an anti-platelet therapy currently recommended as a treatment option for patients at risk of a secondary stroke.

Approximately 35,850 people in England, Wales and Northern Ireland have a non-minor stroke every year.

An estimated 32% of people in the UK have at least one of the highlighted CYP2C19 gene variants, and evidence has suggested that those with these variants have an increased risk of another stroke when taking clopidogrel.

If the genotype test discovers that patients have one of the CYP2C19 gene variants, alternative stroke-prevention treatments would be offered.

Professor Jonathan Benger, chief medical officer at NICE, said: Recommending a genetic test that can offer personalised care to thousands of people who have a stroke each year will be a step forward in ensuring people receive the best possible treatment.

People who are currently taking clopidogrel will not receive retrospective testing and should continue with the treatment until they and their NHS clinician consider it appropriate to stop, NICE outlined.

It added that laboratory-based CYP2C19 genotype testing is its preferred option, followed by the Genedrive CYP2C19 ID Kit point-of-care test and, if neither of the first two options are available, the Genomadix Cube point-of-care test would be used.

The agencys committee has suggested that a phased rollout could be implemented when introducing laboratory-based testing, with testing set to initially be offered to people with a higher risk of stroke recurrence.

Juliet Bouverie, from the Stroke Association, said: Stroke devastates lives and leaves people with life-long disability.

We know that many stroke survivors spend the rest of their lives fearing another stroke, so its great to see that more people could be given appropriate help to significantly cut their risk of recurrent stroke.

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NICE backs post-stroke genetic testing to identify most suitable treatment options - PMLiVE

A second consultation on recommendations that clinicians should offer CYP2C19 genotype testing when considering treatment with clopidogrel after an ischaemic stroke or Transient Ischaemic Attack (a mini stroke) has begun today, Wednesday 3 April 2024.

NICE currently recommends clopidogrel as a treatment option for people at risk of a secondary stroke. For some people with certain variations in a gene called CYP2C19 other treatments could work better. The genotype test would identify people who have the gene variants so they can be offered an alternative treatment.

The draft guidance recommends testing only for people who have very recently had a stroke or TIA. This is because the risk of another event is higher at this time and therefore so is the potential benefit of testing. As the risk of a recurrent stroke or a mini stroke reduces over time, so does the benefit of testing.

For this reason, those people already taking clopidogrel will not be offered retrospective testing.

People who are currently taking clopidogrel should continue with the treatment until they and their NHS clinician consider it appropriate to stop.

Laboratory-based CYP2C19 genotype testing was the committees preferred option followed by the Genedrive CYP2C19 ID Kit point-of-care test. If neither of the first two options are available, the Genomadix Cube point-of-care test can be used.

The NICE committee suggested that a phased rollout could be used when introducing laboratory-based testing with testing initially offered to people with a higher risk of stroke recurrence who would benefit most from it, such as people who have had a non-minor stroke. The committee recognised that it will take time to build up the testing capacity as no testing is currently undertaken to find out if clopidogrel is a suitable treatment.

Around 35,850 people in England, Wales and Northern Ireland have a non-minor stroke each year.

An estimated 32% of people in the UK have at least one of the highlighted CYP2C19 gene variants. They are more common in people with an Asian family background but can be found in people of any ethnicity. Evidence has suggested that people with these variants have an increased risk of another stroke when taking clopidogrel compared to those without them.

If the test discovers they have one of the CYP2C19 gene variants, the person can be treated with another medicine to prevent future strokes.

Around 11 million items of clopidogrel are dispensed each year at a cost of around 16 million to the NHS.

Professor Jonathan Benger, chief medical officer at NICE, said:Recommending a genetic test that can offer personalised care to thousands of people who have a stroke each year will be a step forward in ensuring people receive the best possible treatment.

We recognise that capacity within laboratories will need to increase before everyone who has had a new stroke or mini-stroke can receive testing. While point of care testing is an alternative, our committee has identified that initially those people who could benefit most from laboratory-based testing are those who have had a non-minor stroke.

Anyone who is currently being treated with clopidogrel should continue with the treatment. They should only stop after discussing the options with their clinician.

Juliet Bouverie, from the Stroke Association, said:"Stroke devastates lives and leaves people with life-long disability. We know that many stroke survivors spend the rest of their lives fearing another stroke, so it's great to see that more people could be given appropriate help to significantly cut their risk of recurrent stroke.

"Getting on the right medication and taking it as advised can really go far to prevent further strokes. If you have been prescribed clopidogrel, you need to keep taking it. If you're worried about your risk of another stroke, you should speak to your doctor."

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NICE launches second consultation on genetic testing to guide treatment after a stroke - NICE

CRISPR technology offers the promise to cure human genetic diseases with gene editing. This promise became a reality when the worlds first CRISPR therapy was approved by regulators to treat patients with sickle cell disease and beta-thalassemia last year.

American biopharma Vertex Pharmaceuticals CASGEVY works by turning on the BCL11A gene, which codes for fetal hemoglobin. While this form of hemoglobin is produced before a baby is born, the body begins to deactivate the gene after birth. As both sickle cell disease and beta-thalassemia are blood disorders that affect hemoglobin, by switching on the gene responsible for fetal hemoglobin production, CASGEVY presents a curative, one-time treatment for patients.

As CASGEVYs clearance is a significant milestone, the technology has come a long way. CRISPR/Cas9 was first used as a gene-editing tool in 2012. Over the years, the technology exploded in popularity thanks to its potential for making gene editing faster, cheaper, and easier than ever before.

CRISPR is short for clustered regularly interspaced short palindromic repeats. The term makes reference to a series of repetitive patterns found in the DNA of bacteria that form the basis of a primitive immune system, defending them from viral invaders by cutting their DNA.

Using this natural process as a basis, scientists developed a gene-editing tool called CRISPR/Cas that can cut a specific DNA sequence by simply providing it with an RNA template of the target sequence. This allows scientists to add, delete, or replace elements within the target DNA sequence. Slicing a specific part of a genes DNA sequence with the help of the Cas9 enzyme, aids in DNA repair.

This system represented a big leap from previous gene-editing technologies, which required designing and making a custom DNA-cutting enzyme for each target sequence rather than simply providing an RNA guide, which is much simpler to synthesize.

CRISPR gene editing has already changed the way scientists do research, allowing a wide range of applications across multiple fields. Here are some of the diseases that scientists aim to tackle using CRISPR/Cas technology, testing its possibilities and limits as a medical tool.

Cancer is a complex, multifactorial disease, and a cure remains elusive. There are hundreds of different types of cancer, each with a unique mutation signature. CRISPR technology is a game-changer for cancer research and treatment as it can be used for many things, including screening for cancer drivers, identifying genes and proteins that can be targeted by cancer drugs, cancer diagnostics, and as a treatment.

China spearheaded the first in-human clinical trials using CRISPR/Cas9 as a cancer treatment. The study tested the use of CRISPR to modify immune T cells extracted from a patient with late-stage lung cancer. The gene-editing technology was used to remove the gene that encodes for a protein called PD-1 that some tumor cells can bind to to block the immune response against cancer. This protein found on the surface of immune cells is the target of some cancer drugs termed checkpoint inhibitors.

CRISPR technology has also been applied to improve the efficacy and safety profiles of cancer immunotherapy, such as CAR-T cell and natural killer cell therapies. In the U.S., CRISPR Therapeutics is one of the leading companies in this space, developing off-the-shelf, gene-edited T cell therapies using CRISPR, with two candidates targeting CD19 and CD70 proteins in clinical trials.

In 2022, the FDA granted Orphan Drug designation to Intellia Therapeutics CRISPR/Cas9-gene-edited T cell therapy for acute myeloid leukemia (AML). Currently, Vor BioPharmas VOR33 is undergoing phase 2 trials to treat AML, and the CRISPR trial is one to watch, according to a report published by Clinical Trials Arena earlier this year.

However, CRISPR technology still has limitations, including variable efficiency in the genome-editing process and off-target effects. Some experts have recommended that the long-term safety of the approach remain under review. Others have suggested using more precise gene-editing approaches such as base editing, an offshoot of CRISPR that hit the clinic in the U.S. last year.

There are several ways CRISPR could help us in the fight against AIDS. One is using CRISPR to cut the viral DNA that the HIV virus inserts within the DNA of immune cells. This approach could be used to attack the virus in its hidden, inactive form, which is what makes it impossible for most therapies to completely get rid of the virus.

The first ever patient with HIV was dosed with a CRISPR-based gene-editing therapy in a phase 1/2 trial led by Excision Biotherapeutics and researchers at the Lewis Katz School of Medicine at Temple University in Philadelphia back in 2022.

The decision to move the therapy to the clinic was bolstered by the success of an analog of the drug EBT-101 called EBT-001 in rhesus macaques infected with simian immunodeficiency virus (SIV). In a phase 1/2 study, EBT-101 was found to be safe.

Another approach could make us resistant to HIV infections. A small percentage of the worlds population is born with a natural resistance to HIV, thanks to a mutation in a gene known as CCR5, which encodes for a protein on the surface of immune cells that HIV uses as an entry point to infect the cells. The mutation changes the structure of the protein so that the virus is no longer able to bind to it.

This approach was used in a highly controversial case in China in 2018, where human embryos were genetically edited to make them resistant to HIV infections. The experiment caused outrage among the scientific community, with some studies pointing out that the CRISPR babies might be at a higher risk of dying younger.

The general consensus seems to be that more research is needed before this approach can be used in humans, especially as recent studies have pointed out this practice can have a high risk of unintended genetic edits in embryos.

Cystic fibrosis is a genetic disease that causes severe respiratory problems. Cystic fibrosis can be caused by multiple different mutations in the target gene CFTR more than 700 of which have been identified making it difficult to develop a drug for each mutation. With CRISPR technology, mutations that cause cystic fibrosis can be individually edited.

In 2020, researchers in the Netherlands used base editing to repair CFTR mutations in vitro in the cells of people with cystic fibrosis without creating damage elsewhere in their genetic code. Moreover, aiming to strike again with yet another win is the duo Vertex Pharmaceuticals and CRISPR Therapeutics, which have collaborated to develop a CRISPR-based medicine for cystic fibrosis. However, it might be a while until it enters the clinic as it is currently in the research phase.

Duchenne muscular dystrophy is caused by mutations in the DMD gene, which encodes for a protein necessary for the contraction of muscles. Children born with this disease experience progressive muscle degeneration, and existing treatments are limited to a fraction of patients with the condition.

Research in mice has shown CRISPR technology could be used to fix the multiple genetic mutations behind the disease. In 2018, a group of researchers in the U.S. used CRISPR to cut at 12 strategic mutation hotspots covering the majority of the estimated 3,000 different mutations that cause this muscular disease. Following this study, Exonics Therapeutics was spun out to further develop this approach, which was then acquired by Vertex Pharmaceuticals for approximately $1 billion to accelerate drug development for the disorder. Currently, Vertex is in the research stage, and is on a mission to restore dystrophin protein expression by targeting mutations in the dystrophin gene.

However, a CRISPR trial run by the Boston non-profit Cure Rare Disease targeting a rare DMD mutation resulted in the death of a patient owing to toxicity back in November 2022. Further research is needed to ensure the safety of the drug to treat the disease.

Huntingtons disease is a neurodegenerative condition with a strong genetic component. The disease is caused by an abnormal repetition of a certain DNA sequence within the huntingtin gene. The higher the number of copies, the earlier the disease will manifest itself.

Treating Huntingtons can be tricky, as any off-target effects of CRISPR in the brain could have very dangerous consequences. To reduce the risk, scientists are looking at ways to tweak the genome-editing tool to make it safer.

In 2018, researchers at the Childrens Hospital of Philadelphia revealed a version of CRISPR/Cas9 that includes a self-destruct button. A group of Polish researchers opted instead for pairing CRISPR/Cas9 with an enzyme called nickase to make the gene editing more precise.

More recently, researchers at the University of Illinois Urbana-Champaign used CRISPR/Cas13, instead of Cas9, to target and cut mRNA that codes for the mutant proteins responsible for Huntingtons disease. This technique silences mutant genes while avoiding changes to the cells DNA, thereby minimizing permanent off-target mutations because RNA molecules are transient and degrade after a few hours.

In addition, a 2023 study published in Nature went on to prove that treatment of Huntingtons disease in mice delayed disease progression and that it protected certain neurons from cell death in the mice.

With CASGEVYs go-ahead to treat transfusion-dependent beta-thalassemia and sickle cell disease in patients aged 12 and older, this hints that CRISPR-based medicines could even be a curative therapy to treat other blood disorders like hemophilia.

Hemophilia is caused by mutations that impair the activity of proteins that are required for blood clotting. Although Intellia severed its partnership with multinational biopharma Regeneron to advance its CRISPR candidate for hemophilia B a drug that was recently cleared by the FDA to enter the clinic the latter will take the drug ahead on its own.

As hemophilia B is caused by mutations in the F9 gene, which encodes a clotting protein called factor IX (FIX), Regenerons drug candidate uses CRISPR/Cas9 gene editing to place a copy of the F9 gene in cells in order to get the taps running for FIX production.

The two biopharmas will continue their collaboration in developing their CRISPR candidate to treat hemophilia A, which manifests as excessive bleeding because of a deficit of factor VIII. The therapy is currently in the research phase.

While healthcare companies were creating polymerase chain reaction (PCR) tests to screen for COVID-19 in the wake of the pandemic, CRISPR was also being put to use for speedy screening. A study conducted by researchers in China in 2023, found that the CRISPR-SARS-CoV-2 test had a comparable performance with RT-PCR, but it did have several advantages like short assay time, low cost, and no requirement for expensive equipment, over RT-PCRs.

To add to that, the gene editing tool could fight COVID-19 and other viral infections.

For instance, scientists at Stanford University developed a method to program a version of the gene editing technology known as CRISPR/Cas13a to cut and destroy the genetic material of the virus behind COVID-19 to stop it from infecting lung cells. This approach, termed PAC-MAN, helped reduce the amount of virus in solution by more than 90 percent.

Another research group at the Georgia Institute of Technology used a similar approach to destroy the virus before it enters the cell. The method was tested in live animals, improving the symptoms of hamsters infected with COVID-19. The treatment also worked on mice infected with influenza, and the researchers believe it could be effective against 99 percent of all existing influenza strains.

As European, U.S., and U.K. regulators have given their stamp of approval for the first-ever CRISPR-based drug to treat patients, who is to say we wont see another CRISPR-drug hitting this milestone in the near future.

And apart from the diseases mentioned, CRISPR is also being studied to treat other conditions like vision and hearing loss. In blindness caused by mutations, CRISPR gene editing could eliminate mutated genes in the DNA and replace them with normal versions of the genes. Researchers have also demonstrated how getting rid of the mutations in the Atp2b2 and Tmc1 genes helped partially restore hearing.

However, one of the biggest challenges to turn CRISPR research into real cures is the many unknowns regarding the potential risks of CRISPR therapy. Some scientists are concerned about possible off-target effects as well as immune reactions to the gene-editing tool. But as research progresses, scientists are proposing and testing a wide range of approaches to tweak and improve CRISPR in order to increase its efficacy and safety.

Hopes are high that CRISPR technology will soon provide a way to address complex diseases such as cancer and AIDS, and even target genes associated with mental health disorders.

New technologies related to CRISPR research:

This article was originally published in June 2018, and has since been updated by Roohi Mariam Peter.

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Seven diseases that CRISPR technology could cure - Labiotech.eu

ZUG, Switzerland and BOSTON, April 01, 2024 (GLOBE NEWSWIRE) -- CRISPR Therapeutics(Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, today announced an oral presentation at the American Society of Gene & Cell Therapy (ASGCT) 2024 Annual Meeting, taking place May 7 11, 2024, in Baltimore, MD and virtually.

Title: Development of an In Vivo Non-Viral Ocular Editing Platform and Application to Potential Treatments for Glaucoma Session Type: In-Person Oral Presentation Session Title: Ophthalmic and Auditory: Delivery Innovations Abstract Number:87 Location: Room 318 323 Session Date and Time: Wednesday, May 8, 2024, 1:30 p.m. 3:15 p.m. ET

Abstracts will be released to the public on April 22, 2024, at 4:30 p.m. ET at https://annualmeeting.asgct.org/. The data are embargoed until 6:00 a.m. ET on the presentation day, Wednesday May 8, 2024. A copy of the presentation will be available at http://www.crisprtx.com once the presentation concludes.

About CRISPR Therapeutics Since its inception over a decade ago, CRISPR Therapeutics has transformed from a research-stage company advancing programs in the field of gene editing, to a company with a diverse portfolio of product candidates across a broad range of disease areas including hemoglobinopathies, oncology, regenerative medicine, cardiovascular and rare diseases. The Nobel Prize-winning CRISPR science has revolutionized biomedical research and represents a powerful, clinically validated approach with the potential to create a new class of potentially transformative medicines. To accelerate and expand its efforts, CRISPR Therapeutics has established strategic partnerships with leading companies including Bayer and Vertex Pharmaceuticals. CRISPR Therapeutics AG is headquartered in Zug, Switzerland, with its wholly-owned U.S. subsidiary, CRISPR Therapeutics, Inc., and R&D operations based in Boston, Massachusetts and San Francisco, California, and business offices in London, United Kingdom. To learn more, visit http://www.crisprtx.com.

Investor Contact: Susan Kim +1-617-307-7503 susan.kim@crisprtx.com

Media Contact: Rachel Eides +1-617-315-4493 rachel.eides@crisprtx.com

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CRISPR Therapeutics to Present at the American Society of Gene & Cell Therapy (ASGCT) 2024 Annual Meeting - GlobeNewswire

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Surgery team ICREC-IGTP

Credit: IGTP

The promising results obtained in a clinical trial with a pioneering advanced therapy drug named PeriCord, which aims to repair the heart of patients who have suffered a heart attack, confirm the feasibility of new therapies based on the application of stem cells and tissue engineering to promote the regeneration of damaged tissues.

This new medicine, derived from umbilical cord and pericardium stem cells from tissue donors, is a world-first tissue engineering product (a type of advanced therapy combining cells and tissues optimised in the laboratory). The drug is applied in patients undergoing coronary bypass, utilising the procedure to repair the scar in the heart area affected by the infarction, which has lost the ability to beat when blood flow stopped.

Thefirst interventionof this new therapy was almost 4 years ago, resulting from a collaboration between the ICREC Group (Heart Failure and Cardiac Regeneration) at Germans Trias i Pujol Research Institute (IGTP) and Banc de Sang i Teixits (BST). Following its success, a study was initiated to demonstrate its clinical safety. The study included 12 coronary bypass candidates, 7 treated with bioimplants and 5 without, to compare the outcomes.

Dr Antoni Bays, ICREC researcher and first author of the article:"This pioneering human clinical trial comes after many years of research in tissue engineering, representing a very innovative and hopeful treatment for patients with a heart scar resulting from a heart attack", referring to PeriCord.

While the current study aimed to demonstrate the safety of this new drug in the context of myocardial infarction, its positive outcomes have shown that PeriCord possesses other exceptional properties. It has proven to be a medicine with excellent biocompatibility, drastically minimising the risk of rejection and ensuring perfect tolerance by the body. Additionally, it has anti-inflammatory properties, paving the way for broader applications in pathologies involving inflammation."Its potential could be much wider; we believe it can be a valuable tool for modulating inflammatory processes", explains Dr Sergi Querol, head of the Cellular and Advanced Therapies Service at BST.

Severe but stable patients

The patients included in the therapy are individuals who have suffered a heart attack and have reduced quality and life expectancy. The bypass ensures blood circulation in the area, and the bioimplant goes a step further to stimulate the scar, initiating cellular mechanisms involved in tissue repair.

"Voluntarily provided substances of human origin are used, both in terms of multi-tissue donor pericardial tissue and mesenchymal stem cells from umbilical cord donors at the birth of a baby", explains Querol. It is very gratifying to think that"thanks to this and the donors, we provide a new therapeutic tool that can improve a patient's quality of life", he adds.

PeriCord consists of a membrane that comes from the pericardium of a tissue donor, which BST has decellularised and lyophilised. It has then been recellularised with these umbilical cord stem cells.

Once in the operating theatre, surgeons attach the laboratory-generated bioimplant to the affected area of the patient's heart. After a year, the implanted tissue adheres and adapts perfectly to the structure of the heart, covering the scar left by the heart attack.

Randomized controlled/clinical trial

People

Implantation of a double allogeneic human engineered tissue graft on damaged heart: insights from the PERISCOPE phase I clinical trial

14-Mar-2024

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First cardiac bioimplants for the treatment of patients with myocardial infarction using umbilical cord stem cells - EurekAlert

Sign up for CNNs Stress, But Less newsletter.Our six-part mindfulness guide will inform and inspire you to reduce stress while learning how to harness it.

There is no doubt that stress is a part of everyday life, but too much can have detrimental impacts on peoples physical and mental health.

I wanted to delve more into depth about the health impacts of stress during National Stress Awareness Month. What does stress do to the body? When does it become a problem, and what are some ways to cope with it? And what can people do with stressors such as a hard job or caregiving responsibilities that cant just go away?

To help us answer these questions, I had a conversation with CNN wellness expert Dr. Leana Wen. Wen is an emergency physician and adjunct associate professor at George Washington University. She previously served as Baltimores health commissioner.

CNN: What does stress do to a persons body?

Dr. Leana Wen: When people experience a perceived threat, a variety of hormones are released that make the heart beat faster and increase blood pressure and blood sugar. These hormones also divert energy away from other parts of the body, such as the immune system and digestive system. These are evolutionary adaptations that once helped people to respond to situations such as predators chasing after them. Such fight or flight responses are normal and may be helpful in modern-day life. For instance, they could help an athlete with a faster performance or a student with staying up to study for an exam.

The problem arises when the bodys stress response is continuous. A perpetual state of fight or flight could lead to many chronic problems. Individuals could experience anxiety and depression, and other mental health ailments. They could also have headaches, muscle tension, abdominal pain, sleep disturbances, decreased immunity to infections, and problems with memory and concentration. Chronic stress has also been linked to increased likelihoods of high blood pressure, diabetes, heart attack and stroke.

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CNN: Everyone experiences stress, so when does it become a problem?

Wen: Its natural for people to experience stress to discrete stressful events (those that have a clear onset such as the birth of a child, starting of a new job, a divorce or the death of a loved one) that happen in their lives. The problem is when stress becomes a chronic state of being.

Warning signs to look out for include signs or symptoms of mental health concerns or physical manifestations of stressfor instance, if someone starts having new heart palpitations, abdominal pain or headaches. In addition, some people may attempt to cope with stress by using alcohol or drugs. A change in substance use could be a red flag to look for underlying stressors.

People should also ask themselves if stress is negatively affecting their function at home, at work and with their friends. Someone who finds themselves unusually irritable and is lashing out at loved ones and colleagues may also be doing so because of excessive stress.

CNN: Why should we be aware of excessive stress and try to reduce it as a health priority?

Wen: We can think of stress as something in our lives that is modifiable, just like high blood pressure or high blood sugar. The stressor itself may not be able to be changed, just as we cannot change our genetic predisposition to hypertension or diabetes. However, our reaction to it is within our control. And its our reaction to the stressor that determines our health outcomes. If stress has detrimental effects on our health, just as high blood pressure and diabetes do, then we can and should look for ways to reduce these effects.

CNN: What are some ways we can cope with stress?

Wen: First, its important to clarify that there are good and bad ways to cope with stress. Some people may turn to these not-so-good ways because it may help them feel better in the short-term, but there are real risks. I mentioned drinking alcohol and using drugsobviously, these are not healthy coping strategies. Neither are binge-eating or smoking.

I think its really important to be self-aware. Be honest with yourself: When you have faced stressful situations in the past, have you turned to these unhealthy ways to cope? If so, be on the lookout and work to prevent these behaviors during stressful times.

Also, try to anticipate when there will be stressful situations. Is there a big deadline at work coming up? A family gathering that is likely to elicit negative emotions? A difficult conversation with a loved one? Knowing that a stressful event may occur can help you anticipate your reaction and plan accordingly.

I advise, too, that people make a list of stress relief techniques that have worked for them in the past. And try new techniques. Deep breathing exercises are something everyone can try and help both in the moment of the stressful encounter and after, for example, as is mindfulness meditation.

Im also a big fan of exercise. There is excellent scientific evidence that exercise is very effective at managing stress. Exercise reduces stress hormones and increases endorphins, which are feel-good neurotransmitters that can relax the body and improve mood.

CNN: What is your advice for people who have stressors in their livessuch as a hard job or caregiving responsibilitiesthat cant easily go away?

Wen: This is really hard, because of course it would be ideal to address the stressors themselves. But many people have stressful situations that they cant change.

It helps to be up front about that and acknowledge that changing the situation is not in your control. What is in your control, though, is your reaction to the situation.

Here is where self-awareness and self-care are so important. Learn to recognize when you are feeling especially stressed. Perhaps you feel tension in your neck and back muscles, or you have abdominal cramps or jitters. These are the times to practice deep breathing, meditation and other exercises that help you in the short-term.

For both short- and long-term benefit, its essential to make time for self-care. By that, I mean activities that you enjoy and that can take your mind off the stressful life situations. These could include taking a walk with a good friend, working in the garden, playing with your pets, reading a good book or otherwise participating in activities you enjoy. Think of the time you are putting aside for yourself as a kind of therapy; stress can make you unhealthy, so this is your way of giving yourself treatment to offset that stress.

Along those lines, knowing that stress is one factor that can impact your well-being, work to maximize the other aspects that contribute to overall health. Try to get adequate, restful sleep. Aim to eat healthy, whole foods and reduce your consumption of ultra-processed products. Make sure other chronic medical conditions, such as high blood pressure, are being treated. And do not wait to seek help from your mental health or primary care provider if the stress you are experiencing is leading to continuing mental health or physical distress.

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What people should know about stress, according to a doctor - Yahoo Singapore News

Pharmac Te Ptaka Whaioranga has issued a request for proposals (RFP) asking suppliers to bid for the supply of oestradiol gel in New Zealand.

Pharmac is looking to fund a new type of oestradiol treatment without restrictions, says Dr David Hughes, Pharmacs Director Advice and Assessment/Chief Medical Officer.

In the past three years, the supply issues for oestradiol patches has caused stress and frustration for New Zealanders. Demand has more than doubled - growing from 1.2 million patches dispensed in 2020/21 to over 3 million patches in 2022/23.

Our clinical advisors have told us that funding another oestradiol product would be useful because demand is increasing, and we are continuing to experience global supply issues for oestradiol patches. We know that some people would use the gel if its funded, and this could relieve some of the stress on the supply of patches.

Oestradiol is used by 85,000 people each year for the treatment of a range of conditions including, menopause, osteoporosis, and gender affirming health care. It is most often used as a patch placed on the skin, but it is also available as a tablet.

We want to make sure people get the treatment they need, and which can be funded from Pharmacs fixed budget, so were keen to hear from suppliers about what they can offer, says Dr Hughes.

Dr Linda Dear, a menopause specialist says, Its wonderful to hear that another step is being taken towards giving perimenopausal and menopausal New Zealanders fully funded access to oestradiol (estrogen) gels.

This will provide a much-needed alternative, so people are no longer solely reliant on the patches as the only funded transdermal option available. Having gels as an alternative will ease the pressure of the supply issue which has had an impact on New Zealanders using the treatments, pharmacists, and prescribing doctors alike. My hope is that we dont have to wait too much longer to access this important therapy.

Pharmacs job is to assess and prioritise which treatments will deliver the best possible health outcomes for New Zealanders from the available budget, says Dr Hughes.

"Once this RFP closes, an evaluation committee will meet to consider the bids received. We will also seek advice from our clinical advisors. As this activity progresses, well share more information with the public.

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Pharmac seeking bids from suppliers to fund another type of hormone replacement therapy - New Zealand Doctor Online