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Cells Responsible for Hair Growth Discovered – Wall Street Pit

Its one of those times when serendipity went to work. As a team of UT Southwestern Medical Center researchers were studying a rare form of genetic cancer called Neurofibromatosis Type 1 that causes tumors to grow on nerves, what they discovered instead were hair progenitor cells. Essentially, these are the cells that cause hair to grow. With this new information on hand, the path towards managing hair growth problems, including hair discoloration (a.k.a greying of hair) now seems to have become clearer.

As explained by Dr. Lu Le, one of the researchers and currently an Associate Professor of Dermatology: With this knowledge, we hope in the future to create a topical compound or to safely deliver the necessary gene to hair follicles to correct these cosmetic problems.

Prior to this discovery, researchers were already aware that skin stem cells located in the bulge on bottom of hair follicles were involved, in one way or another, in the growth of hair. What they didnt know was how these skin cells turn into hair cells, specifically, what happens after those cells move down to the bulb or the base of hair follicles. This also meant they had no idea what to do to stimulate and manipulate their growth.

As they were studying the nerve cells and how tumors formed on them, they discovered a protein that differentiates the skin stem cells from other types of cells. The protein is called KROX20 and as far as they knew, this protein was more commonly associated with nerve development. In the hair follicles of their mice test subjects, however, they found out that KROX20 becomes activated in the skin cells which eventually turn into hair shafts that cause hair to grow. That said, though, its not as simple as that.

It turned out that KROX20 works in tandem with another protein called SCF (short for stem cell factor) and without either one, hair growth happens abnormally, or not at all.

When KROX20 turns on in a skin cell, it causes the cell to produce SCF. With both proteins now active, they move up the hair bulb, interact with melanocyte cells (the cells that produce pigment), and grow into healthy, colored hairs.

When the team removed the KROX20-producing cells, the mice did not grow any hair, meaning, they became bald. And when they removed the SCF gene, the mices hair started out as gray-colored, then turned white with age.

From these results, the obvious way forward is to backtrack whats happening, possibly try to figure out why and how aging affects KROX20 protein production. Another aspect that will also be looked at is the reason why the SCF gene stops functioning, thereby resulting in gray hair production. The findings could also help provide answers on why hair loss and graying of hair are among the first indications of aging.

The research was recently published in the journal Genes & Development.

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Can CRISPR feed the world? | Horizon: the EU Research … – Horizon magazine

By 2040, there will be 9 billion people in the world. Thats like adding another China onto todays global population, said Professor Sophien Kamoun of the Sainsbury Laboratory in Norwich, UK.

Prof. Kamoun is one of a growing number of food scientists trying to figure out how to feed the world. As an expert in plant pathogens such asPhytophthora infestans the fungus-like microbe responsible for potato blight he wants to make crops more resistant to disease.

Potato blight sparked the Irish famine in the 19th century, causing a million people to starve to death and another million migrants to flee. European farmers now keep the fungus in check by using pesticides. However, in regions without access to chemical sprays, it continues to wipe out enough potatoes to feed hundreds of millions of people every year.

Potato blight is still a problem, said Prof. Kamoun. In Europe, we use 12 chemical sprays per season to manage the pathogen that causes blight, but other parts of the world cannot afford this.

Plants try to fight off the pathogens that cause disease but these are continuously changing to evade detection by the plants immune system.

Arms race

In nature, every time a plant gets a little better at fighting off infection, pathogens adapt to evade their defences. Now biologists are getting involved in the fight.

Its essentially an arms race between plants and pathogens, said Prof. Kamoun. We want to turn it into an arms race between biotechnologists and pathogens by generating new defences in the lab.

If we think of the genome as text, CRISPR is a word processor that allows us to change just a letter or two.

Prof. Sophien Kamoun, Sainsbury Laboratory, UK

Five years ago, Prof. Kamoun embarked on a project called NGRB, funded by the EU’s European Research Council. The plan was to find a way to make potatoes more resistant to infection using advanced plant-breeding techniques.

Then serendipity struck. In the early stages of the project, scientists in another lab discovered a ground-breaking gene-editing technique known as CRISPR-Cas which allows scientists to delete or add genes at will. As well as having potential medical applications in humans, this powerful tool is unlocking new approaches to perfecting plants.

If we think of the genome as text, CRISPR is a word processor that allows us to change just a letter or two, explained Prof. Kamoun. The precision that this allows makes CRISPR the ultimate in genetic editing. Its really beautiful.

One of the simplest ways to use CRISPR to improve plants is to remove a gene that makes them vulnerable to infection. This alone can make potatoes more resilient, helping to meet the worlds growing demand for food.

The resulting crop looks and tastes just the same as any other potato. Prof. Kamoun says that potatoes which are missing a gene or two should not be viewed in the same way as genetically modified foods which sometimes contain genes introduced from another species. Its a very important technical difference but not all regulators have updated their rules to make this distinction.

Potatoes are not the only food crops that can be improved by CRISPR-Cas. Prof. Kamoun is now working on a project that aims to protect wheat from wheat blast a fungal disease decimating yields in Bangladesh and spreading in Asia.

Looking ahead, CRISPR will be used to improve the quality and nutritional value of wheat, rice, potatoes and vegetables. It could even be used to remove genes that cause allergic reactions in people with tomato or wheat intolerance.

If we can remove allergens, consumers may soon see hypoallergenic tomatoes on supermarket shelves, Prof. Kamoun said. Its a very exciting technology.

While targeting disease in this way could be a game changer for global food security in the years ahead, experts believe other approaches to plant breeding will continue to have a role. Understanding meiosis a type of cell division that can reshuffle genes to improve plants can help farmers and the agribusiness sector select for hardier crops, according to Professor Chris Franklin of the University of Birmingham, UK.

He leads the COMREC project, which trains young scientists to understand and manipulate meiosis in plants. The project applies the wealth of knowledge generated by leaders in the field to tackle the pressing problem of feeding a hungry world.

COMREC has begun to translate fundamental research into (applications in) key crop species such as cereals, brassicas and tomato, said Prof. Franklin. Close links with plant-breeding companies have provided important insight into the specific challenges confronted by the breeders.

Elite crops

There may be untapped potential in this approach to plant breeding: most of the genes naturally reshuffled during meiosis in cereal crops are at the far ends of chromosomes genes in the middle of chromosomes are rarely reshuffled, limiting the scope for new crop variations.

COMRECs academic and industry partners hope to understand why this is so that they can find a way to shuffle the genes in the middle of chromosomes too. And the food industry is keen to produce new elite varieties that are better adapted to confront the challenges arising from climate change, says Prof. Franklin.

A number of genes have now been identified that can make this reshuffling relatively more frequent, he said. CRISPR-Cas provides a way to modify the corresponding genes in crop species, helping to translate this basic research to target crops.

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This UK Biotech uses CRISPR-Cas9 To Fight Bacterial Resistance – Labiotech.eu (blog)

This week we went back to one of our favourite biotech hubs in the UK: Cambridge. Here, a young startup called Nemesis Bioscience is working on new treatment strategies to fight antimicrobial resistance based on CRISPR-Cas9.

Mission: Nemesis strategy is different from that of most companies in the antibiotic resistance space. Instead of developing new antibiotics to kill bacteria, the biotech aims to switch off resistance mechanisms and thereby resurrect antibiotic susceptibility. The Cybergenetics technologies use bacteriophages to deliver programmable RNA-guided endonucleases into the bacteria.

The nuclease can then inactivate antibiotic resistance genes and restore antibiotic activity. Nemesis first nuclease is directed against 8 families of beta-lactamases and is thereby able to inactivate resistance to beta-lactam antibiotics.

Comment: By targeting resistance genes directly, the biotech believes it is able to offset the natural selection pressure, which would eventually result in resistance to new antibiotic drugs. Swiss Bioversys is testing a similar approach, although the biotechs platform is based on small molecules.

Also, Nemesis technology represents yet another exciting therapeutic application of the CRISPR-Cas9 system. Because the endonuclease is delivered using bacteriophages, it is specifically targeted to bacteria, and not mammalian cells. Thereby, the technology overcomes the risk of off-target effects, which are currently limiting the therapeutic use of CRISPR.

Images via shutterstock.com / e X p o s e and nemesisbio.com

Merken

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This UK Biotech uses CRISPR-Cas9 To Fight Bacterial Resistance – Labiotech.eu (blog)

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Hypogonadism Treatment & Management: Approach …

In prepubertal patients with hypogonadism, treatment is directed at initiating pubertal development at the appropriate age. Age of therapy initiation takes into account the patient’s psychosocial needs, current growth, and growth potential. Treatment entails hormonal replacement therapy with sex steroids, ie,estrogen for females and testosterone for males.

Introduction of sex steroids in such cases startswith the use ofsmall, escalating doses over a period of a couple of years. In females, introduction of puberty can begin with administration of small doses of estrogen given either orally or transdermally. One traditional regimen uses conjugated estrogen startingat doses as low as 0.15 mg daily and titrating upwards in 6-12 month intervals to typically 0.625 mg daily, at which point menses can be induced with the introduction of a progestin. Alternatively, transdermal 17-estradiol (0.08 to 0.12 mcg estradiol/kg) can be used.

In boys, introduction of puberty is achieved with the use of testosterone, administered intramuscularly or transdermally (in the form of a patch or gel). A typical regimen involves testosterone enanthate injections 50 mg monthly, titrating up to 200-250 mg every 2 weeks, which is a typical adult replacement dose. Adult testosterone dose can be adjusted to maintain serum testosterone concentrations in the normal adult range.

Therapy with sexsteroid replacement ensures development of secondary sexual characteristics and maintenance of normal sexual function. In patients with hypergonadotropic hypogonadism, fertility is not possible. However, patients with hypogonadotropic hypogonadism have fertilitypotential,although therapy with sex steroids does not confer fertility or stimulate testicular growth in men.An alternative for men with hypogonadotropic hypogonadism has been treatment with pulsatile LHRH or hCG, either of which can stimulate testicular growth and spermatogenesis.

Because such treatment is more complex than testosterone replacement, and because treatment with testosterone does not interfere with later therapy to induce fertility, most male patients with hypogonadotropic hypogonadism prefer to initiate and maintain virilization with testosterone.At a time when fertility is desired, it may be induced with either pulsatile LHRH or (more commonly) with a schedule of injections of hCG and FSH. Similarly, fertility can be achieved in females with pulsatile LHRH or exogenous gonadotropin. Such therapy results in ovulation in 95% of women.

A phase III, multicenter, open-label, single-arm trial by Nieschlag et al indicated that corifollitropin-alfa therapy combined with hCG treatment can significantly increase testicular volume and induce spermatogenesis in adult males with hypogonadotropic hypogonadism whose azoospermia could not be cured by hCG treatment alone. Patients in the study who remained azoospermic, though with normalized testosterone levels, after 16 weeks of hCG treatment underwent 52 weeks of twice-weekly hCG therapy along with every-other-week corifollitropin-alfa treatment (150 g). Mean testicular volume in these patients rose from 8.6 mL to 17.8 mL, while spermatogenesis was induced in more than 75% of subjects. [9]

The use of oral testosterone preparations, such as 17-alkylated androgens (eg, methyltestosterone), is discouraged because of liver toxicity. However, oral testosterone undecanoate is available in some countriesand is now approved in the United States. Intramuscular testosterone is available as testosterone enanthate or cypionate. Transdermal testosterone can be administered either in the form of a patch or gel. A nasal testosterone replacement therapy has been approved by the US Food and Drug Administration (FDA) for adult males with conditions such as primary hypogonadism (congenital or acquired) and hypogonadotropic hypogonadism (congenital or acquired) resulting from a deficiency or absence of endogenous testosterone. [10] The recommended dosage is 33 mg/day in three divided doses. The drug has not been approved for males younger than 18 years.

For older men with testosterone deficiency, a review by the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) found that the evidence concerning the risk of serious cardiovascular side effects from the use of testosterone in men with hypogonadism was inconsistent. [11, 12] The PRAC determined that the benefits of testosterone outweigh its risks but stressed that testosterone-containing medicines should be used only when lack of testosterone has been confirmed by signs and symptoms, as well as by laboratory tests. However,a literature review by Albert and Morley indicated that testosterone supplementation in males aged 65 years or older may increase the risk of cardiovascular events, particularly during the first year of treatment, althoughintramuscular testosterone seemed to carry less risk than other forms. [13]

On the other hand,a study by Traish et al suggested that long-term testosterone therapy in men with hypogonadism significantly reduces cardiovascular diseaserelated mortality. Patients in the studys testosterone-treated group (n=360) underwent therapy for up to 10 years, with median follow-up being 7 years. The investigators found no cardiovascular eventrelated deaths in the treated patients, compared with 19 such deaths in the group that received no testosterone therapy (n=296). According to the study, mortality in the testosterone-treated patients was reduced by an estimated 66-92%. [14]

The latest Endocrine Society clinical practice guidelines suggest testosterone therapy for men receiving high doses of glucocorticoids who also have low testosterone levels, to promote bone health. The guidelines also suggest such therapy in human immunodeficiency virus (HIV)infected men with low testosterone levels, to maintain lean bone mass and muscle strength.

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Hypogonadism Treatment & Management: Approach …

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Cancer drug class has cardiac benefits – BioWorld Online

By Anette Breindl Senior Science Editor

“With the advent of targeted cancer therapies, what we’ve found is that many of them are cardiotoxic,” Saptarsi Haldar told BioWorld Today. “Pathways that are effective in cancer are toxic in the heart.”

In the May 17, 2017, issue of Science Translational Medicine, Haldar, who is an associate investigator at the Gladstone Institute of Cardiovascular Disease, and his colleagues showed that a class of epigenetic drugs, the BET bromodomain inhibitors, may be not just an exception to that rule, but a class of drugs that has therapeutic utility in heart failure.

The team showed that the bromodomain inhibitor JQ-1 had therapeutic benefits in two separate animal models of advanced heart failure, but did not affect the beneficial changes to heart muscle cells that are a consequence of exercise.

The paper shows a potential new approach to heart failure an indication that, with a five-year survival rate of 60 percent, needs them.

It also shows a potential approach to another vexing problem, namely drugging transcription factors.

“There’s a surprisingly tractable therapeutic index for drugging transcription in diseases,” Haldar said.

While BRD4 is not itself a transcription factor, inhibiting it “dampens the transcription factor-driven network that’s driving the disease . . . This is really about dampening transcriptional rewiring,” he added.

In heart failure, those happen to be innate immune signaling and fibrotic signaling. Experiments in cardiac cells derived from induced pluripotent stem cells (iPSCs) showed that JQ-1 acted by blocking the activation of innate immune and profibrotic pathways, essentially preventing heart cells from rewiring themselves in maladaptive ways in response to being chronically overworked.

Haldar said the original idea to test whether the compound would have an effect in heart failure was based on “an educated guess.”

Previous work had shown that certain epigenetic marks, namely acetyl marks on lysines, play a role in heart failure.

“There is a lot known about lysine acetylation in heart failure,” Haldar said, and there had been previous attempts at targeting the process, which had “fallen to the wayside, in part because of issues with therapeutic index.”

Even studying the molecular details of lysine acetylation’s role in heart failure was challenging, because genetic approaches are not viable.

The problem became tractable with the synthesis of JQ-1 in the laboratory of James Bradner, who is a co-author on the Science Translational Medicine paper. The compound, which has been used to gain insight into epigenetic aspects of a large number of biological processes thanks to the decision of its developers to distribute it freely, targets BRD4, a “reader” protein that recognizes acetylated lysines. (See BioWorld Insight, Aug. 12, 2013.)

With the advent of JQ-1, Haldar said, “we immediately made the connection that here’s a target BRD4 that you could specifically modulate that is recognizing acetyl-lysines on chromatin.”

The team initially published work in 2013 showing that JQ-1 affected cellular processes in heart failure, and was an effective therapeutic in mice when given very early in the disease.

Patients, though, don’t show up in their doctor’s office very early in the disease. They show up with “pre-existing, often chronic heart failure,” Haldar said.

At that point, the heart has already undergone significant remodeling that includes fibrosis and an activation of innate immune pathways.

The work now published in Science Translational Medicine showed that JQ-1 had effects even when given to mice that had established heart failure either due to a heart attack, or pressure overload, but did not block exercise-induced remodeling.

The team is hoping to test JQ-1 derivatives in large animal models, and ultimately take them into the clinic. Haldar is a co-founder of Tenaya Therapeutics Inc., a company launched in December with a $50 million series A financing from The Column Group. Haldar said that while he holds a patent on BET protein inhibition in heart disease, BET proteins are only “one of many targets/pathways that Tenaya is considering.”

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Scientists get closer to making personalized blood cells by using patients’ own stem cells – Los Angeles Times

New research has nudged scientists closer to one of regenerative medicines holy grails: the ability to create customized human stem cells capable of forming blood that would be safe for patients.

Advances reported Wednesday in the journal Nature could not only give scientists a window on what goes wrong in such blood cancers as leukemia, lymphoma and myeloma. They could also improve the treatment of those cancers, which affect some 1.2 million Americans.

The stem cells that give rise to our blood are a mysterious wellspring of life. In principle, just one of these primitive cells can create much of a human beings immune system, not to mention the complex slurry of cells that courses through a persons arteries, veins and organs.

While the use of blood-making stem cells in medicine has been common since the 1950s, it remains pretty crude. After patients with blood cancers have undergone powerful radiation and chemotherapy treatments to kill their cancer cells, they often need a bone-marrow transplant to rebuild their white blood cells, which are destroyed by that treatment.

The blood-making stem cells that reside in a donors bone marrow and in umbilical cord blood that is sometimes harvested after a babys birth are called hematopoietic, and they can be life-saving. But even these stem cells can bear the distinctive immune system signatures of the person from whom they were harvested. As a result, they can provoke an attack if the transplant recipients body registers the cells as foreign.

This response, called graft-versus-host disease, affects as many as 70% of bone-marrow transplant recipients in the months following the treatment, and 40% develop a chronic version of the affliction later. It can overwhelm the benefit of a stem cell transplant. And it kills many patients.

Rather than hunt for a donor whos a perfect match for a patient in need of a transplant a process that can be lengthy, ethically fraught and ultimately unsuccessful doctors would like to use a patients own cells to engineer the hematopoietic stem cells.

The patients mature cells would be reprogrammed to their most primitive form: stem cells capable of becoming virtually any kind of human cell. Then factors in their environment would coax them to become the specific type of stem cells capable of giving rise to blood.

Once reintroduced into the patient, the cells would take up residence without prompting rejection and set up a lifelong factory of healthy new blood cells.

If the risk of deadly rejection episodes could be eliminated, physicians might also feel more confident treating blood diseases that are painful and difficult but not immediately deadly diseases such as sickle cell disease and immunological disorders with stem cell transplants.

The two studies published Wednesday demonstrate that scientists may soon be capable of pulling off the sequence of operations necessary for such treatments to move ahead.

One of two research teams, led by stem-cell pioneer Dr. George Q. Daley of Harvard Medical School and the Dana Farber Cancer Institute in Boston, started their experiment with human pluripotent stem cells primitive cells capable of becoming virtually any type of mature cell in the body. Some of them were embryonic stem cells and others were induced pluripotent stem cells, or iPS cells, which are made by converting mature cells back to a flexible state.

The scientists then programmed those pluripotent stem cells to become endothelial cells, which line the inside of certain blood vessels. Past research had established that those cells are where blood-making stem cells are born.

Here, the process needed a nudge. Using suppositions gleaned from experiments with mice, Daley said his team confected a special sauce of proteins that sit on a cells DNA and program its function. When they incubated the endothelial cells in the sauce, they began producing hematopioetic stem cells in their earliest form.

Daleys team then transferred the resulting blood-making stem cells into the bone marrow of mice to see if they would take. In two out of five mice who got the most promising cell types, they did. Not only did the stem cells establish themselves, they continued to renew themselves while giving rise to a wide range of blood cells.

A second research team, led by researchers from Weill Cornell Medicines Ansary Stem Cell Institute in New York, achieved a similar result using stem cells from the blood-vessel lining of adult mice. After programming those cells to revert to a more primitive form, the scientists also incubated those stem cells in a concoction of specialized proteins.

When the team, led by Raphael Lis and Dr. Shahin Rafii, transferred the resulting stem cells back into the tissue lining the blood vessels of the mice from which they came, that graft also took. For at least 40 weeks after the incubated stem cells were returned to their mouse owners, the stem cells continued to regenerate themselves and give rise to many blood-cell types without provoking immune reactions.

In addition to making a workhorse treatment for blood cancers safer, the new advances may afford scientists a unique window on the mechanisms by which blood diseases take hold and progress, said Lee Greenberger, chief scientific officer for the Leukemia and Lymphoma Society.

From a research point of view you could now actually begin to model diseases, said Greenberger. If you were to take the cell thats defective and make it revert to a stem cell, you could effectively reproduce the disease and watch its progression from the earliest stages.

That, in turn, would make it easier to narrow the search for drugs that could disrupt that disease process early. And it would speed the process of discovering which genes are implicated in causing diseases. With gene-editing techniques such as CRISPR-Cas9, those offending genes could one day be snipped out of hematopoietic stem cells, then be returned to their owners to generate new lines of disease-free blood cells.

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Scientists get closer to making personalized blood cells by using patients’ own stem cells – Los Angeles Times

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Rock band encourages fans to become bone marrow donors – ITV.com – ITV News

Welsh rockers The Alarm are using their shows to encourage fans to become bone marrow donors.

The band, who are set to play at the Electric Ballroom in London, on Saturday, have arranged for swabbing station to be set up at the venue.

It means fans will be able to join a bone marrow donor registry with a simple cheek swab.

Leader singer Mike Peters, who has battled cancer three times, co-founded the Love Hope Strength Foundation in 2007 with the aim to “save lives, one concert at a time”.

It hosts donor drives at concerts and festivals around the world by encouraging music fans aged 18 to 55 to sign up to the International Bone Marrow Registry.

To date, more than 150,000 music fans have joined the registry, and more than 3,100 potentially-lifesaving matches for blood cancer patients.

Bone marrow is a soft tissue found in the middle of certain bones. It contains stem cells, which are the “building blocks” for other normal blood cells (like red cells, which carry oxygen, and white cells, which fight infection).

Some diseases, such as leukaemia, prevent people’s bone marrow from working properly. And for certain patients, the only cure is to have a stem cell transplant from a healthy donor.

Peters, 58, from North Wales, was first diagnosed with Hodgkin lymphoma in 1995. He has also battled leukaemia twice.

He said: “It’s humbling to see how many people have responded to the Get On The List campaign so far.”

Blood cancer charity DKMS, which is the world’s largest donor centre, has worked with the LHS Foundation since 2013.

Joe Hallett, senior donor recruitment manager at the charity, said: “Only one in three people with a blood cancer in the UK and in need of a life-saving blood stem cell transplant will be lucky enough to find a suitable match within their own family.

“Finding a match from a genetically similar person can offer the best treatment, a second chance of life.”

Last updated Fri 19 May 2017

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6-year-old thalassemia patient from Punjab meets his stem cell … – Times of India

BENGLURU: Fateh Singh, a six-year-old thalassemia major patient from Amritsar, underwent a bone marrow transplant last May which gave him a new lease of life. A year later, the boy met his saviour, Naval Chaudhary, whose stem cells were used for the procedure. The child was diagnosed with the condition when he was one-and-a-half years old.

On Thursday, the donor and recipient met for the first time. Naval, 28, a professional living in Bengaluru, had registered with DATRI, an unrelated blood stem cell donors registry in 2015. He said: “I was very happy to hear I was a potential match for a patient. But then I was told the donation process had to be done through bone marrow harvesting. Initially, I was a tad hesitant but then I researched the procedure and was counselled by Dr Sunil Bhat, paediatric haemato-oncologist from Mazumdar Shaw Cancer Centre.”

“I realized that saving a life is more important than the type of procedure I had to go through. So I decided to go ahead,” he added.

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6-year-old thalassemia patient from Punjab meets his stem cell … – Times of India

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Exercise can even burn off fat in bone marrow – Futurity: Research News

Exercise can burn the fat found within bone marrow, according to new research. The work, conducted with mice, offers evidence that this process improves bone quality and increases the amount of bone in a matter of weeks.

The study, published in the Journal of Bone and Mineral Research, also suggests obese individualswho often have worse bone qualitymay derive even greater bone health benefits from exercising than their lean counterparts.

One of the main clinical implications of this research is that exercise is not just good, but amazing for bone health, says lead author Maya Styner, a physician and assistant professor of endocrinology and metabolism at the University of North Carolina at Chapel Hill. In just a very short period of time, we saw that running was building bone significantly in mice.

Although research in mice is not directly translatable to the human condition, the kinds of stem cells that produce bone and fat in mice are the same kind as those that produce bone and fat in humans.

In addition to its implications for obesity and bone health, Styner says the research also could help illuminate some of the factors behind bone degradation associated with conditions like diabetes, arthritis, anorexia, and the use of steroid medications.

I see a lot of patients with poor bone health, and I always talk to them about what a dramatic effect exercise can have on bones, regardless of what the cause of their bone condition is, says Styner. With obesity, it seems that you get even more bone formation from exercise. Our studies of bone biomechanics show that the quality and the strength of the bone is significantly increased with exercise and even more so in the obese exercisers.

Bone marrow coordinates the formation of bone and cartilage while simultaneously churning out blood cells, immune cells, and cancerous cells.

Marrow also produces fat, but the physiological role of bone marrow fat in the bodyand even whether it is beneficial or harmful for ones healthhas remained somewhat mysterious.

Generally, marrow fat has been thought to comprise a special fat reserve that is not used to fuel energy during exercise in the same way other fat stores are used throughout the body during exercise. The new study offers evidence to the contrary.

Styners work also offers fundamental insights on how marrow fat forms and the impact it has on bone health. Previous studies have suggested that a higher amount of marrow fat increases the risk of fractures and other problems.

Theres been intense interest in marrow fat because its highly associated with states of low bone density, but scientists still havent understood its physiologic purpose, says Styner. We know that exercise has a profound effect on fat elsewhere in the body, and we wanted to use exercise as a tool to understand the fat in the marrow.

The researchers performed their experiments in two groups of mice. One group was fed a normal diet (lean mice) and the other received a high-fat diet (obese mice) starting a month after birth. When they were four months old, half the mice in each group were given a running wheel to use whenever they liked for the next six weeks. Because mice like to run, the group with access to a wheel tended to spend a lot of time exercising.

The researchers analyzed the animals body composition, marrow fat, and bone quantity at various points. Predictably, the obese mice started with more fat cells and larger fat cells in their marrow. After exercising for six weeks, both obese and lean mice showed a significant reduction in the overall size of fat cells and the overall amount fat in the marrow. In these respects, the marrow fat of exercising obese mice looked virtually identical to the marrow fat of lean mice, even those that exercised.

Perhaps more surprising was the dramatic difference in the number of fat cells present in the marrow, which showed no change in lean mice but dropped by more than half in obese mice that exercised compared to obese mice that were sedentary. The tests also revealed that exercise improved the thickness of bone, and that this effect was particularly pronounced in obese mice.

According to Styner, all of this points to the conclusion that marrow fat can be burned off through exercise and that this process is good for bones.

Obesity appears to increase a fat depot in the bone, and this depot behaves very much like abdominal and other fat depots, says Styner. Exercise is able to reduce the size of this fat depot and burn it for fuel and at the same time build stronger, larger bones.

The research leaves a few lingering mysteries. A big one is figuring out the exact relationship between burning marrow fat and building better bone. It could be that when fat cells are burned during exercise, the marrow uses the released energy to make more bone. Or, because both fat and bone cells come from parent cells known as mesenchymal stem cells, it could be that exercise somehow stimulates these stem cells to churn out more bone cells and less fat cells.

More research will be needed to parse this out. What we can say is theres a lot of evidence suggesting that marrow fat is being used as fuel to make more bone, rather than there being an increase in the diversion of stem cells into bone, says Styner.

Coauthors of the study are from UNC and State University of New York, Stony Brook. The National Institutes of Health Funded this research.

Source: UNC-Chapel Hill

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Athlone mother’s desperate search for bone marrow donor for son (3) – Eyewitness News

Athlone mother’s desperate search for bone marrow donor for son (3)

Raqeeb Palm was diagnosed with Aplastic Anaemia in October after his mother noticed unusual bruises on his body.

Three-year-old Raqeeb Palm was diagnosed with Aplastic Anaemia in October after his mother noticed unusual bruises on his body. Picture: Monique Mortlock/EWN.

CAPE TOWN A mother from Heideveld in Athlone is desperately trying to find a bone marrow donor for her three-year-old son.

Raqeeb Palm was diagnosed with Aplastic Anaemia in October after his mother noticed unusual bruises on his body.

The boy had to undergo various blood tests and two bone marrow biopsies over a two-month period, before being diagnosed with the rare disease which damages bone marrow and stem cells.

Zaida Palm says her outgoing child can no longer play outside or do many of the activities three-year-olds enjoy due to his severely weakened immune system.

Hes got practically no immune system. So going out, malls, play areas, doing fun things is on a stop. Because any germ, he gets admitted [to the hospital] for a cold, he needs to go to the hospital.

Palm says they have been unable to find a bone marrow donor in South Africa.

A transplant is her son’s only chance of survival.

Her medical aid won’t cover an investigation for international donors, which is why she’s turned to online crowd-funding.

The hundred thousand on the Backabuddy [website] is just the start to the campaign.

Palm has also urged people to become bone marrow donors.

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Athlone mother’s desperate search for bone marrow donor for son (3) – Eyewitness News

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Can Skin Cells Create a Baby? – National Catholic Register

Nation | May. 19, 2017

New and controversial potential fertility technology called in vitro gametogenesis has caused pushback from some critics.

WASHINGTON Within the next 10-20 years, a new and controversial potential fertility technology called in vitro gametogenesis (IVG) could make it possible to manipulate skin cells into creating a human baby.

However, this groundbreaking research has caused pushback from some critics, like Father Tadeusz Pacholczyk, director of education at the National Catholic Bioethics Center, who says IVG would turn procreation into a transaction.

IVG extends the faulty logic of IVF [in vitro fertilization] by introducing additional steps to the process of manipulating the origins of the human person, in order to satisfy the desires of customers and consumers, Father Pacholczyk told CNA in an email interview.

The technology also offers the possibility of introducing further fractures into parenthood, distancing children from their parents by multiplying the number of those involved in generating the child, so that three-parent embryos, or even more parents, may become involved, he continued.

IVG has been successfully tested by Japanese researchers on mice, which produced healthy babies derived from skin cells.

The process begins by taking the skin cells from the mouses tail and reprograming them to become induced pluripotent stem cells. These manipulated cells are able to grow into different kinds of cells and are then used to grow eggs and sperm, which are then fertilized in the lab. The resulting embryos are then implanted in a womb.

Although similar to in vitro fertilization, IVG eliminates the step of needing pre-existing egg and sperm and instead creates these gametes.

But many experts in the reproductive field are skeptical of potential outcomes and ethical compromises.

It gives me an unsettled feeling because we dont know what this could lead to, Paul Knoepfler, a stem-cell researcher at the University of California, Davis,told The New York Times.

Knoepfler noted that some of the potential repercussions of IVG could turn into cloning or designer babies. Other dangers could include the Brad Pitt scenario, in which celebritys skin cells retrieved from random places, like hotel rooms, could be used to create a baby.

Potentially anyones skin cells could be used to create a baby, even without their knowledge or consent.

Inan issue ofScience Translational Medicineearlier this year, a trio of academics a Harvard Law professor, the dean of Harvard Medical School and a medical science professor at Brown University wrote that IVG may raise the specter of embryo farming on a scale currently unimagined, which might exacerbate concerns about the devaluation of human life.

They added that refining the science of IVG to the point of clinical use will involve the generation and likely destruction of large numbers of embryos from stem cellderived gametes, and the process may exacerbate concerns regarding human enhancement.

Father Pacholczyk also pointed to further concerns, saying IVG disrupts the uniqueness of every individuals sex cells.

IVG raises additional concerns because of the way it manipulates human sex cells. Our sex cells, or gametes, are special cells. They uniquely identify us, Father Pacholczyk stated.

It is most unfortunate that overwhelming parental desires are being permitted to trump and distort the right order of transmitting human life, he continued.

Father Pacholczyk said that processes like IVG enable a consumerist mentality that holds that children are projects to be realized through commercial transactions and laboratory techniques of gamete manipulation.

The Catholic Church teaches that IVF and similar reproductive technologies are morally illicit for several reasons, including their separation of procreation from the conjugal act and the creation of embryos which are discarded.

Pope Francis recently spoke out against the destruction of human embryos, saying that no good result from research can justify the destruction of embryos.

Some branches of research use human embryos, inevitably causing their destruction. But we know that no ends, even noble in themselves such as a predicted utility for science, for other human beings or for society can justify the destruction of human embryos,the Holy Father said May 18.

Although IVG has proven successful in mice, human testing is likely years away.

However, Father Pacholczyk hopes that potential parents will come to realize that children should not be viewed as products that can be ordered or purchased by consumers, but seen as a gift.

Turning commercial laboratories to create children on our behalf is an unethical step in the direction of treating our offspring as objects to be planned and created in the pursuit of parental gratification, rather than gifts received from the Lord.

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Can Skin Cells Create a Baby? – National Catholic Register

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renovacareinc.com – The Christian Institute

The new technique heals burns much faster and more effectively than traditional skin grafting.

Burn victims may no longer be forced to undergo painful skin grafts, thanks to a revolutionary piece of technology that uses adult stem cells.

Instead of taking skin from one part of the body and transplanting it onto the burned area, a stem-cell spraying device simply covers the affected area with the victims own stem cells.

By taking adult stem cells from a healthy section of skin, placing them in a solution, and spraying the solution onto the wound, the patients own skin grows back and heals naturally.

The procedure has been in development for some time, and is not yet commercially available, but its capability was publicised in the press earlier this month.

The technology was featured in the Journal of the International Society for Burn Injuries, and showed incredible before and after images of the horrific injuries, and the victims almost full recoveries.

Patients who have benefitted from early treatments say their new skin is virtually indistinguishable from the rest of their body.

Commenting on the journals research, Thomas Bold, CEO of RenovaCare a company developing this technology said, the skin that regrows looks, feels and functions like the original skin.

By using adult stem cells, the healing process of the victims was also vastly accelerated.

While a skin graft treatment can take weeks or even months, and leave scarring, these patients were able to grow healthy skin in as little as four days.

In one case, a man who had suffered electrical burns to over a third of his body after touching a live wire had 24 million adult stem cells harvested and then sprayed back onto his body.

The process itself lasted only 90 minutes, and within four days, he had regrown a thin layer of skin over his arms and chest, where the burns were least severe.

After 20 days, all of the areas treated by the stem cell grafting process were described as completely healed.

RenovaCare is applying for a licence to use the technology in routine practice in Europe.

In January, it was revealed that a new technique allowed adult stem cells to be used in the treatment of heart problems.

The technique involves implanting synthetic cardiac stem cells which repair heart muscle. It has been praised as both an ethical and less risky alternative to other treatments.

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Babies from skin cells? Advance unsettles experts – The Hindu


The Hindu
Babies from skin cells? Advance unsettles experts
The Hindu
It gives me an unsettled feeling because we don't know what this could lead to, said Paul Knoepfler, a stem cell researcher at the University of California, Davis. You can imagine one man providing both the eggs and the sperm, almost like cloning

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Babies from skin cells? Advance unsettles experts – The Hindu

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Researchers Get Closer to First Lab-Grown Blood Stem Cells – Vital Updates

After two decades of research, scientists are on the cusp of entering a new era in stem-cell research that may transform the landscape of genetics and disease therapy.

In a first-ever clinical trial, researchers from Harvard University have created blood-forming stem cells, which they hope can one day serve to ameliorate genetic blood disorders and other conditions.

Were tantalizingly close to generating bona fide human blood stem cells in a dish, said senior investigator George Q. Daley, Dean of Harvard Medical School and head of a research lab in the Stem Cell Program at Boston Childrens Hospital. This work is the culmination of over 20 years of striving.

While scientists first isolated embryonic stem cells in 1998, they have found little success in the years since in using them to create legitimate blood-forming stem cells.

However, Daley tapped into years of work that had been done previously, including his teams creation of the first induced pluripotent stem (iPS) cells in 2007. While the team previously was able to use the iPS cells to produce other kinds of human cells, including brain and heart cells, they had no luck in their pursuit of blood-forming cells.

Related:Arthritis Vaccine Could Emerge From Stem Cell Technology

That is, until now. And the breakthrough puts them on pace to make a tremendous impact on patients with genetic disease, according to the study authors.

This step opens up an opportunity to take cells from patients with genetic blood disorders, use gene editing to correct their genetic defect and make functional blood cells, said study author Ryohichi Sugimura, a postdoctoral fellow in the Daley lab.

Currently, the approach of the Harvard researchers includes using viruses to alter the genetic material within the blood-forming cells that they have created. But their ultimate goal is to expand their ability to make true blood stem cells in a way thats practice[sp] and safe, without the need for viruses to signal genetic change.

Their new research may have cleared one long-standing barrier in the way of that realization.

Its proved challenging to see these cells, said Sugimura. You can roughly characterize blood stem cells based on surface markers, but even with this, it may not be a true blood stem cell. And once it starts to differentiate and make blood cells, you cant go back and study it its already gone.

Related:Scientists Grow Beating Heart Cells on Spinach Leaves

A better characterization of human blood stem cells and a better understanding of how they develop would give us clues to making bona fide human blood stem cells, added Sugimura.

To test the potency of their new approach, the Harvard team transplanted blood-forming cells into mice. After several weeks, some of the mice carried multiple types of human blood cells in their bone marrow and circulating blood, which means that the cells were actively working to create new blood cells within the animals bodies.

Were now able to model human blood function in so-called humanized mice, said Daley. This is a major step forward for our ability to investigate genetic blood disease.

The study appears online in the journal Nature.

A professional journalist nearly 30 years, David Heitz started his career at the Quad-City Times in Davenport, Iowa before moving to Los Angeles. He led the Glendale News-Press to best small daily newspaper in the state (CNPA) as managing editor and also worked as executive news editor of the Press-Telegram. He worked briefly as deputy news editor of the Detroit News before returning to the Quad-Cities, where he has worked as a freelance medical writer since 2012 for several national websites. He recently purchased his childhood home and says he truly is living the dream.

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Fixing the Tomato: CRISPR Edits Correct Plant-Breeding Snafu … – Scientific American

From their giant fruits to compact plant size, todays tomatoes have been sculpted by thousands of years of breeding. But mutations linked to prized traitsincluding one that made them easier to harvestyield an undesirable plant when combined, geneticists have found.

It is a rare example of a gene harnessed during domestication that later hampered crop improvement efforts, says geneticist Zachary Lippman of Cold Spring Harbor Laboratory in New York. After identifying the mutations, he and his colleagues used CRISPR gene editing to engineer more productive plantsa strategy that plant breeders are eager to adopt.

Its pretty exciting, says Rod Wing, a plant geneticist at the University of Arizona in Tucson. The approach can be applied to crop improvement, not just in tomato, but in all crops.

Lippman knows his way around a tomato farm. As a teenager, he spent his summers picking the fruit by handa chore he hated. Rotten tomatoes. The smell lasts all day long, he says. I would always pray for rain on tomato-harvest day.

But years later, his interest in the genetics that control a plants shape led him back to tomato fields, to untangle the genetic changes that breeders had unknowingly made.

In the 1950s, researchers found a new trait in a wild tomato relative growing in the Galpagos Islands: it lacked the swollen part of the stem called the joint.

Joints are weak regions of the stem that allow fruit to drop off the plant. Wild plants benefit from dropping fruit because it helps seed dispersal. But with the advent of mechanical tomato pickers, farmers wanted their fruit to stay on the plant. Breeders rushed to incorporate the jointless trait into their tomatoes.

This new trait came with a downside. When it was crossed into existing tomato breeds, the resulting plants had flower-bearing branches that produced many extra branches and looked like a broom, terminating in a host of flowers. The flowers were a drain on plant resources, diminishing the number of fruits it produced. Breeders selected for other genetic variants that overrode this defect. But decades later, Lippman’s team went looking for the genes behind this phenomenon.

They had previously screened a collection of 4,193 varieties of tomato, looking for those with unusual branching patterns. From that collection, they tracked down variants of two genes that, together, caused extreme branching similar to what plant breeders had seen. One of the two genes, the team reports in a paper published online inCellon 18 May, is responsible for the jointless trait.

The other gene favours the formation of a large green cap of leaf-like structures on top of the fruita trait that was selected for thousands of years ago, in the early days of tomato domestication. The benefits of this trait are unclear, Lippman says, but it may have helped to support heavier fruits.

With these genes uncovered, his team used CRISPRCas9 editing to eliminate their activity, as well as that of a third gene that also affects flower number, in various combinations. This generated a range of plant architectures, from long, spindly flower-bearing branches to bushy, cauliflower-like bunches of flowersincluding some with improved yields.

The findings should help to quell lingering doubts among plant breeders that negative interactions between desirable genetic traits are a force to be reckoned with, says Andrew Paterson, a plant breeder at the University of Georgia in Athens. The idea has been controversial, he says, because the effects have been difficult to detect statistically.

Lippmans team is now working with plant breeders to use gene editing to develop tomatoes with branches and flowers optimized for the size of the fruit. Plants with larger fruit, for example, may have better yields if they have fewer flowering branches than those with smaller fruit.

We really are tapping into basic knowledge and applying it to agriculture, he says. And ironically, it happens to be in the crop that I least liked harvesting on the farm.

This article is reproduced with permission and wasfirst publishedon May 18, 2017.

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Fixing the Tomato: CRISPR Edits Correct Plant-Breeding Snafu … – Scientific American

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Beyond just promise, CRISPR is delivering in the lab today – The Conversation US

Precision editing DNA allows for some amazing applications.

Theres a revolution happening in biology, and its name is CRISPR.

CRISPR (pronounced crisper) is a powerful technique for editing DNA. It has received an enormous amount of attention in the scientific and popular press, largely based on the promise of what this powerful gene editing technology will someday do.

CRISPR was Science magazines 2015 Breakthrough of the Year; its been featured prominently in the New Yorker more than once; and The Hollywood Reporter revealed that Jennifer Lopez will be the executive producer on an upcoming CRISPR-themed NBC bio-crime drama. Not bad for a molecular biology laboratory technique.

CRISPR is not the first molecular tool designed to edit DNA, but it gained its fame because it solves some longstanding problems in the field. First, it is highly specific. When properly set up, the molecular scissors that make up the CRISPR system will snip target DNA only where you want them to. It is also incredibly cheap. Unlike previous gene editing systems which could cost thousands of dollars, a relative novice can purchase a CRISPR toolkit for less than US$50.

Research labs around the world are in the process of turning the hype surrounding the CRISPR technique into real results. Addgene, a nonprofit supplier of scientific reagents, has shipped tens of thousands of CRISPR toolkits to researchers in more than 80 countries, and the scientific literature is now packed with thousands of CRISPR-related publications.

When you give scientists access to powerful tools, they can produce some pretty amazing results.

The most promising (and obvious) applications of gene editing are in medicine. As we learn more about the molecular underpinnings of various diseases, stunning progress has been made in correcting genetic diseases in the laboratory just over the past few years.

Take, for example, muscular dystrophy a complex and devastating family of diseases characterized by the breakdown of a molecular component of muscle called dystrophin. For some types of muscular dystrophy, the cause of the breakdown is understood at the DNA level.

In 2014, researchers at the University of Texas showed that CRISPR could correct mutations associated with muscular dystrophy in isolated fertilized mouse eggs which, after being reimplanted, then grew into healthy mice. By February of this year, a team here at the University of Washington published results of a CRISPR-based gene replacement therapy which largely repaired the effects of Duchenne muscular dystrophy in adult mice. These mice showed significantly improved muscle strength approaching normal levels four months after receiving treatment.

Using CRISPR to correct disease-causing genetic mutations is certainly not a panacea. For starters, many diseases have causes outside the letters of our DNA. And even for diseases that are genetically encoded, making sense of the six billion DNA letters that comprise the human genome is no small task. But here CRISPR is again advancing science; by adding or removing new mutations or even turning whole genes on or off scientists are beginning to probe the basic code of life like never before.

CRISPR is already showing health applications beyond editing the DNA in our cells. A large team out of Harvard and MIT just debuted a CRISPR-based technology that enables precise detection of pathogens like Zika and dengue virus at extremely low cost an estimated $0.61 per sample.

Using their system, the molecular components of CRISPR are dried up and smeared onto a strip of paper. Samples of bodily fluid (blood serum, urine or saliva) can be applied to these strips in the field and, because they linked CRISPR components to fluorescent particles, the amount of a specific virus in the sample can be quantified based on a visual readout. A sample that glows bright green could indicate a life-threatening dengue virus infection, for instance. The technology can also distinguish between bacterial species (useful for diagnosing infection) and could even determine mutations specific to an individual patients cancer (useful for personalized medicine).

Almost all of CRISPRs advances in improving human health remain in an early, experimental phase. We may not have to wait long to see this technology make its way into actual, living people though; the CEO of the biotech company Editas has announced plans to file paperwork with the Food and Drug Administration for an investigational new drug (a necessary legal step before beginning clinical trials) later this year. The company intends to use CRISPR to correct mutations in a gene associated with the most common cause of inherited childhood blindness.

Physicians and medical researchers are not the only ones interested in making precise changes to DNA. In 2013, agricultural biotechnologists demonstrated that genes in rice and other crops could be modified using CRISPR for instance, to silence a gene associated with susceptibility to bacterial blight. Less than a year later, a different group showed that CRISPR also worked in pigs. In this case, researchers sought to modify a gene related to blood coagulation, as leftover blood can promote bacterial growth in meat.

You wont find CRISPR-modified food in your local grocery store just yet. As with medical applications, agricultural gene editing breakthroughs achieved in the laboratory take time to mature into commercially viable products, which must then be determined to be safe. Here again, though, CRISPR is changing things.

A common perception of what it means to genetically modify a crop involves swapping genes from one organism to another putting a fish gene into a tomato, for example. While this type of genetic modification known as transfection has actually been used, there are other ways to change DNA. CRISPR has the advantage of being much more programmable than previous gene editing technologies, meaning very specific changes can be made in just a few DNA letters.

This precision led Yinong Yang a plant biologist at Penn State to write a letter to the USDA in 2015 seeking clarification on a current research project. He was in the process of modifying an edible white mushroom so it would brown less on the shelf. This could be accomplished, he discovered, by turning down the volume of just one gene.

Yang was doing this work using CRISPR, and because his process did not introduce any foreign DNA into the mushrooms, he wanted to know if the product would be considered a regulated article by the Animal and Plant Health Inspection Service, a division of the U.S. Department of Agriculture tasked with regulating GMOs.

APHIS does not consider CRISPR/Cas9-edited white button mushrooms as described in your October 30, 2015 letter to be regulated, they replied.

Yangs mushrooms were not the first genetically modified crop deemed exempt from current USDA regulation, but they were the first made using CRISPR. The heightened attention that CRISPR has brought to the gene editing field is forcing policymakers in the U.S. and abroad to update some of their thinking around what it means to genetically modify food.

One particularly controversial application of this powerful gene editing technology is the possibility of driving certain species to extinction such as the most lethal animal on Earth, the malaria-causing Anopheles gambiae mosquito. This is, as far as scientists can tell, actually possible, and some serious players like the Bill and Melinda Gates Foundation are already investing in the project. (The BMGF funds The Conversation Africa.)

Most CRISPR applications are not nearly as ethically fraught. Here at the University of Washington, CRISPR is helping researchers understand how embryonic stem cells mature, how DNA can be spatially reorganized inside living cells and why some frogs can regrow their spinal cords (an ability we humans do not share).

It is safe to say CRISPR is more than just hype. Centuries ago we were writing on clay tablets in this century we will write the stuff of life.

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Beyond just promise, CRISPR is delivering in the lab today – The Conversation US

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What is CRISPR-Cas9, and will it change the world? | Alphr – Alphr

What is CRISPR-Cas9?

CRISPR-Cas9 is a genome editing tool thats able to cut DNA in a targeted fashion, allowing scientists to accurately edit the building blocks of life.

It was actually first observed in the 1980s as part of single-celled bacterias defence mechanisms, which ensure that the cells are able to remove unwanted intruders. Scientists have found that, by adapting the technology, they are able to target genome sequences with unprecedented speed, precision and accuracy.

Picture CRISPR-Cas9 as like a find and replace search in a computer document, only instead of words, youre editing genetic sequences.

Accurately modifying DNA is a scientific holy grail, and the potential is enormous. It could be used to eradicate diseases even hereditary ones such as cystic fibrosis, sickle-cell anemia and Huntington’s could become a thing of the past.

The name CRISPR is an acronym for the less catchy clustered regularly interspaced short palindromic repeats. The Cas part refers to CRISPR associated.

CRISPR is part of certain bacterias naturally occurring defences. When a bacteria detects an invading virus, it is able to copy and blend segments of the foreign DNA into its own genome around CRISPR.

The next time the virus is spotted, CRISPR has an exact copy of the genome sequence to look out for, which is where the Cas protein comes in: it can cut the DNA up, and disable unwanted genes with incredible accuracy.

Or, as Carl Zimmer explains: As the CRISPR region fills with virus DNA, it becomes a molecular most-wanted gallery, representing the enemies the microbe has encountered. The microbe can then use this viral DNA to turn Cas enzymes into precision-guided weapons. The microbe copies the genetic material in each spacer into an RNA molecule. Cas enzymes then take up one of the RNA molecules and cradle it. Together, the viral RNA and the Cas enzymes drift through the cell. If they encounter genetic material from a virus that matches the CRISPR RNA, the RNA latches on tightly. The Cas enzymes then chop the DNA in two, preventing the virus from replicating.

In 2012, scientists from the University of California, Berkeley, published a groundbreaking paper showing they were able to reprogramme the CRISPR-Cas immune system to edit genes at will. CRISPR-Cas9 uses a specific Cas protein and a hybrid RNA that can identify and edit any gene sequence. The possibilities are huge.

In short, CRISPR lists the DNA sequences to target, and then Cas9 does the cutting. Scientists just need to programme CRISPR with the right code, and Cas9 does the rest.

This could also apply to faulty genes sections currently causing problems could be removed with CRISPR-Cas9, and then replaced with healthy genetic code, theoretically solving the problem.

CRISPR is cutting edge technology, but while its true that its use has massively accelerated in recent years thanks to the above discovery, scientists have actually been aware of it in bacteria since the 1980s. Pubmed lists 5,775 papers discussing CRISPR but 5,575 of those have been in the three years since the UC Berkeley paper, and the number has jumped from 2,071 when I first wrote this article back in October 2015.

CRISPR-Cas9 isnt the first genomic editor, but it has a number of upsides that make it both simpler and far more efficient.

Firstly, CRISPR-Cas9 can edit multiple genes at once, whereas other genome editors such as zinc finger nuclease (ZFN) or transcription activator-like effector nucleases (TALENs) require painstaking modification of a single gene at a time. Its also quicker and cheaper, as you might expect.

Although ZFN and TALENs can recognise longer gene sequences than CRISPR-Cas9, custom proteins have to be created each time and its an inexact science, involving the creation of several variants before the winning combination is found.

On top of that, scientists tend to use ZFN and TALENs with organisms scientists know extremely well such as mice, rats and fruit flies. CRISPR-Cas9 should work with every organism ever evolved. Yes, including humans.

Yes, in China. Using human embryos sourced from a fertility clinic, scientists tried to use CRISPR-Cas9 to edit a gene that causes beta thalassemia in every cell. It should be noted that the donor embryos used were non-viable, and could not have resulted in a live birth.

In any case, it failed, and failed quite badly: 86 embryos were injected, and after 48 hours and around eight cells grown, 71 survived, and 54 of those were genetically tested. Just 28 had been successfully spliced, and very few contained the genetic material the researchers intended. If you want to do it in normal embryos, you need to be close to 100%, lead researcher Jungiu Huang told Nature. Thats why we stopped. We still think its too immature.

On top of that, its extremely likely more undocumented damage was done. As the New York Times explains: The Chinese researchers point out that in their experiment gene editing almost certainly caused more extensive damage than they documented; they did not examine the entire genomes of the embryo cells.

As you might imagine, it caused a huge amount of controversy in the scientific community.

In November 2016, another grouip of Chinese scientists became the first to use CRISPR-Cas9 on an adult human, injecting a lung cancer sufferer with the patient’s immune cells modified by CRISPR to disable the PD-1 protein, theoretically making the patient’s body fight back against the cancer. Results are still yet to be reported. The first American trial of CRISPR in humans is due to take place at the University of Pennsylvania later this year again with cancer.

Even though the Chinese scientists used embryos that were not going to develop into life, there are real ethical concerns about experimenting on human embryos indeed, just a month before the Chinese research was published, a group of American scientists urged the world not to do so.

Part of this comes down to how immature the technology is remember that its only been in active use since 2012, and it would be astonishing if it was fully matured at this point. Scientists warned that it was too misunderstood and dangerous to use on humans at this point, and the Chinese research certainly vindicates this concern. Even if it worked flawlessly, there are concerns that unforeseen consequences could occur over generations.

But, even if it were 100% safe and successful, there are other ethical concerns: while nobody argues that we should hold back the potential of wiping out killer genetic diseases such as Huntingtons and cystic fibrosis, CRISPR-Cas9 potentially offers the opportunity to change anything about a person. As long as the genetic sequence is identified, in theory, it can be edited.

Its one thing to remove life-impacting diseases before birth its quite another for parents to be able to design their babies to be stronger, faster or better looking. Even if you accept that this is something people should be allowed to do, the chances are this would be heavily commercialised, ensuring only the rich could afford all the extra life advantages this would afford, massively affecting inequality.

Of course, these ethical questions are a million miles away when the only recorded embryonic human experiment was such a high-profile set-back. However, CRISPR-Cas9 is now showing extremely promising results in smaller tests.

Examples include HIV infection prevention in human cells, curing genetic mouse diseases and a pair of monkeys born with targeted mutations. As Wired says, it “kills HIV and eats Zika like Pac-man,” with hopes that cancer could be the next disease in its sights.

Yes. Stem cell researchers in the UK sought permission to modify human embryos in an attempt to understand early human development, and reduce the likelihood of miscarriage. In February 2016, theHuman Fertilisation and Embryology Authority (HFEA) granted permission.

As mentioned previously, Cas9 can only recognise genetic sequences of around 20 bases long, meaning that longer sequences cannot be targeted.

More significantly, the enzyme still sometimes cuts in the wrong place. Figuring out why this is will be a significant breakthrough in itself fixing it will be even bigger.

Then, of course, theres the issue that CRISPR didnt work terribly well in human embryos. Scientists need to discover what went wrong there, and what the difference is between the success in single cells and the more patchy results with embryos.

That isnt a simple question to answer. Its subject to an ongoing patent battle surprisingly, given CRISPR is naturally occurring in certain bacteria.

Technology Review explains that, although CRISPR-Cas9 was first described in Science in 2012 by Jennifer Doudna from UC Berkeley, Feng Zhang from the Broad Institute won a patent on the technique by submitting lab notebooks proving hed invented it first.

First to file patent rights means that this should be granted to Doudna, but the decision could have been decided based on first to invent rules, which would have favoured Zhang. In the end, the case was resolved in February 2017, when the US Patent Trial and Appeal Board resolved that UC Berkeley would be granted the patent for the use of CRISPR-Cas9 in any living cell, while Broad would get it in any eukaryotic cell which is to say cells in plants and animals.

Images: Petra B Fritz, VeeDunn, NIH Image Gallery, and Steve Jurvetson used under Creative Commons

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What is CRISPR-Cas9, and will it change the world? | Alphr – Alphr

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A New Potential ALS Gene Therapy Delivers A Key Milestone – ALS Research Forum

About 1 out of 5 inherited cases of ALS occur due to mutations in SOD1. How these genetic changes contribute to ALS remains unclear. But according to a growing number of studies, these mutations result in the misfolding and aggregation of this metabolic enzyme, contributing to motor neuron toxicity by multiple mechanisms (see Taylor et al., 2016).

Silence, please. Scientists are developing gene therapy strategies for SOD1 ALS that aim to reduce levels of mutant SOD1 in key tissues affected by the disease including the brain and spinal cord. [Image: Rice University under a CC BY 4.0 license.]

A growing number of researchers are developing potential treatment strategies that aim to reduce levels of mutant SOD1 in the CNS in hopes to slow or stop the progression of the disease. One approach, which involves gene therapy, suppresses expression of the SOD1 gene through RNA silencing-based mechanisms. This strategy, according to a 2016 study led by University of Massachusetts Medical Schools Christian Mueller, can extend the lifespan of pre-onset adult SOD1 mice by up to 20% upon intrathecal injection (Borel et al., 2016).

Now, Martine Barkats and Maria Grazia Biferi of the Institute of Myology in Paris, France introduce a new gene therapy approach that increases survival of pre-symptomatic adult SOD1 G93A mice by more than 50%. An independent analysis, led by ALS Therapy Development Institutes Fernando Vieira and commissioned by Prize4Life, confirmed the teams results.

The Institute of Myology team received the Prize4Life $1.0 million USD Avi Kremer ALS Treatment Prize in recognition of reaching this key milestone. This is the best efficacy [observed] in a SOD1 mouse, said Nicole Szlezk, Chairman of Prize4Lifes Board of Directors in the US.

Maria Grazia Biferi unveiled the potential treatment strategy on April 25, 2017 at the ALS Association Drug Company Working Group, held during the 69th Annual Meeting of the American Academy of Neurology.

The approach builds on a previous strategy developed by Barkats team, using a related gene therapy delivery vehicle, for spinal muscular atrophy. A similar strategy, known as ChariSMA (AVXS-101), is now at the phase 1 stage and according to interim phase I results appears promising (see December 2015 news).

This is no longer an academic exercise, said Lucie Bruijn, Chief Scientist of the ALS Association. The current clinical trials in SMA confirm that this approach can succeed.

Going viral

In 2007, Martine Barkats team discovered that the recombinant adeno-associated virus AAV9 could penetrate the blood-brain barrier, opening the door to the development of gene therapies for motor neuron diseases. (see December 2008 news; Duque et al., 2009; Foust et al., 2009).

Every dog has its day. Researchers at Tufts University School of Medicine are now evaluating a potential gene therapy for SOD1-linked ALS in dogs. The approach aims to help dogs with a naturally occurring form of the disease known as canine degenerative myelopathy (DM), a late-onset disease first recognized in the 1970s in German Shepards. The trial is a key step toward developing a treatment for ALS, because dogs are larger and the disease is naturally occurring. [Image: Handicapped Pets. CC BY-SA 2.0 license.]

Building on these advances, research teams led by Nationwide Childrens Hospital Brian Kaspar in Ohio and University of Massachusetts Medical Centers Robert Brown began to develop potential therapies for SOD1 ALS. One of these strategies, being developed by Robert Brown and Christian Mueller at the University of Massachusetts Medical School, uses an artificial microRNA to reduce levels of mutant SOD1 synthesis in the brain and spinal cord. The approach is currently being evaluated at the preclinical stage in dogs with degenerative myelopathy (DM), a naturally occurring form of the disease. The clinical trial, being led by Tufts University School of Medicines Dominik Faissler in Massachusetts, launched in December 2016 and is ongoing.

The strategy builds in part, on previous studies led by Martine Barkats which found that AAV10 is more efficient than AAV9 in delivering genes into motor neurons in the spinal cord at lower doses, critical in developing a treatment for a disease (Tanguy et al., 2015). The approach, according to studies led by University of Californias Krystof S. Bankiewicz in San Francisco and University of Massachusetts Medical Centers Christian Mueller can be delivered efficiently intrathecally into motor neurons, at least in non-human primates.

Meanwhile, California Institute of Technologys Ben Deverman and Viviana Gradinaru used Cre-recombination-based AAV targeted evolution (CREATE), to develop novel gene therapy delivery vehicles that penetrate the blood brain barrier, to treat disorders of the central nervous system, including ALS. The vectors, which include AAV-PHP.B, can deliver genes into the motor cortex in the brain and the spinal cord at about 40 times greater efficiency compared to AAV9 upon intravenous injection (Deverman et al., 2016).

The delivery approach is now licensed to Cambridge startup Voyager Therapeutics in Massachusetts, which is also developing a gene therapy for SOD1 ALS. Voyager Therapeutics hopes to file an IND for their potential treatment strategy for ALS, known as VY-SOD101, at the end of 2017.

A key question is whether SOD1 is needed to reduce free radical levels that arise in key tissues affected by the disease. Therefore, a growing number of research teams are developing erase and replace strategies which aim to reduce mutant SOD1 while at the same time, produce the wild-type enzyme to help detoxify key tissues affected by ALS, including the brain, spinal cord and muscles.

A one, two punch?

Engineering a new approach. Researchers at University of Massachusetts Medical School are developing a CRISPR-Cas9-based gene therapy for SOD1-linked ALS that aims to permanently suppress mutant SOD1 synthesis. Meanwhile, Duke Universitys Charles Gersbach is developing a epigenomic editing-based strategy, also presented at AAN 2017, that may be of benefit to a wide range of diseases including the most common forms of ALS, C9orf72-linked disease (see January 2017 conference news; Thakore et al., 2015). [Courtesy of Ran et al., 2013, Nature Publishing Group.]

With the advent of new gene silencing technologies, research teams began to take another look at their gene therapy approaches and began to modify them in hopes to optimize their strategies to combat SOD1-linked disease. Robert Brown turned to CRISPR/Cas9 technologies in hopes to stop further mutant SOD1 synthesis. Their approach, unveiled at AAN 2017, uses imprecise CAS9-based editing to introduce indels in the SOD1 gene. The key obstacle, according to preliminary results presented by University of Massachusetts Medical Schools Zachary Taylor, is delivering sufficient Cas9 to modify the mutant SOD1 gene within motor neurons and glia in the central nervous system. Preclinical studies remain ongoing.

Across the globe, Martine Barkats and Maria Grazia Biferi, are developing a strategy using a novel gene silencing AAV10-based approach to tackle SOD1 ALS. The strategy is now being optimized and is at the preclinical stage. The approach involves the injection of the potential therapy into the blood and the brain. The reason, according to Biferi is to ensure that levels of the misfolded enzyme are reduced in key tissues outside the CNS including skeletal muscle.

This is important, explains Biferi, because ALS is beginning to be considered a multisystemic disease.

Now, the researchers are developing a similar strategy to tackle C9orf72 ALS, the most common form of the disease identified to date.

TARgeting ALS

A detox program for the CNS? Researchers at MeiraGTx in New York, in collaboration with Ronald Klein and Gregory Petsko, are developing a gene therapy strategy that aims to reduce the toxicity of TDP-43 by turning up nonsense-mediated mRNA decay. [Image: Emw, Wikimedia Commons.]

Meanwhile, Louisiana State Universitys Ronald Klein is setting his sights on helping to develop a gene therapy that targets more than 95% of cases of the disease. The approach, based on previous studies led by Gregory Petsko in New York, now at Weill Cornell Medical College in New York and Sami Barmada, now at the University of Michigan, aims to reduce cytoplasmic TDP43-mediated motor neuron toxicity by turning up nonsense-mediated mRNA decay. The gene therapy-based strategy increases levels of hUPF1, a key regulator of this process (see June 2015 news; Ju et al., 2011; Barmada et al., 2015).

The approach, according to a study from Kleins team, prolongs motor function at least for 8 weeks in a rat model of the disease. The study found that the potential therapy, when administered at day 1, preserved strength in the forelimbs of a rat model of ALS (see June 2015 news; Jackson et al., 2015).

It is really amazing that [increasing] hUPF has this really specific protective action against TDP-43, says Klein. We keep seeing it again and again.

How this strategy may mitigate TDP-43-mediated motor neuron toxicity remains unclear. The approach is one of at least two that aims to target TDP-43 buildup in the cytoplasm of motor neurons (see April 2017 news; Becker et al., 2017).

The strategy, now licensed to the New York biotech startup MeiraGTx, is at the preclinical stage. Evaluation of the approach in adult rat models of ALS is ongoing.

References

Borel F, Gernoux G, Cardozo B, Metterville JP, Toro Cabreja GC, Song L, Su Q, Gao GP, Elmallah MK, Brown RH Jr, Mueller C. Therapeutic rAAVrh10 Mediated SOD1 Silencing in Adult SOD1(G93A) Mice and Nonhuman Primates. Hum Gene Ther. 2016 Jan;27(1):19-31. doi: 10.1089/hum.2015.122. [PubMed].

Duque S, Joussemet B, Riviere C, Marais T, Dubreil L, Douar AM, Fyfe J, Moullier P, Colle MA, Barkats M. Intravenous administration of self-complementary AAV9 enables transgene delivery to adult motor neurons. Mol Ther. 2009 Jul;17(7):1187-96. [PubMed].

Foust KD, Nurre E, Montgomery CL, Hernandez A, Chan CM, Kaspar BK. Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes. Nat Biotechnol. 2009 Jan;27(1):59-65 [PubMed].

Tanguy Y, Biferi MG, Besse A, Astord S, Cohen-Tannoudji M, Marais T, Barkats M. Systemic AAVrh10 provides higher transgene expression than AAV9 in the brain and the spinal cord of neonatal mice. Front Mol Neurosci. 2015 Jul 28;8:36. doi: 10.3389/fnmol.2015.00036. eCollection 2015. [PubMed].

Barmada SJ, Ju S, Arjun A, Batarse A, Archbold HC, Peisach D, Li X, Zhang Y, Tank EM, Qiu H, Huang EJ, Ringe D, Petsko GA, Finkbeiner S. Amelioration of toxicity in neuronal models of amyotrophic lateral sclerosis by hUPF1. Proc Natl Acad Sci U S A. 2015 Jun 23;112(25):7821-6. [PubMed].

Jackson KL, Dayton RD, Orchard EA, Ju S, Ringe D, Petsko GA, Maquat LE, Klein RL. Preservation of forelimb function by UPF1 gene therapy in a rat model of TDP-43-induced motor paralysis. Gene Ther. 2015 Jan;22(1):20-8. [PubMed].

Ju S, Tardiff DF, Han H, Divya K, Zhong Q, Maquat LE, Bosco DA, Hayward LJ, Brown RH Jr, Lindquist S, Ringe D, Petsko GA. A yeast model of FUS/TLS-dependent cytotoxicity. PLoS Biol. 2011 Apr;9(4):e1001052. [PubMed].

Becker LA, Huang B, Bieri G, Ma R, Knowles DA, Jafar-Nejad P, Messing J, Kim HJ, Soriano A, Auburger G, Pulst SM, Taylor JP, Rigo F, Gitler AD. Therapeutic reduction of ataxin-2 extends lifespan and reduces pathology in TDP-43 mice. Nature. 2017 Apr 20;544(7650):367-371. [PubMed].

Further Reading

van Zundert B, Brown RH Jr. Silencing strategies for therapy of SOD1-mediated ALS. Neurosci Lett. 2017 Jan 1;636:32-39. [PubMed].

Tora MS, Keifer OP Jr, Lamanna JJ, Boulis NM. The challenges of developing a gene therapy for amyotrophic lateral sclerosis. Expert Rev Neurother. 2017 Apr;17(4):323-325. [PubMed].

AAN2017 c9orf72 disease-als gene therapy SOD1 tdp-43 topic-preclinical topic-randd

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A New Potential ALS Gene Therapy Delivers A Key Milestone – ALS Research Forum

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An Experimental Gene Therapy Uses Viruses to Stop Age-Related … – Futurism

In Brief Researchers from Johns Hopkins Medicine in Maryland have discovered a rather unusual way to treat a severe form of age-related blindness. They found a virus inserted into the retina can be used to halt or even reverse the disease. A Unique Treatment

They say you dont fight fire with fire. However, researchers from Johns Hopkins Medicine in Maryland have found that sometimes a virus may be the best weapon against a disease.Their studyhas been publishedin The Lancet

The researchers werelooking for ways to treat a particular type ofage-related macular degeneration (AMD)known as a wet AMD. Its a rare and more severe form of the disease,affecting just 10 percent of all AMD patients, and it causes new blood vessels to grow under the retina, which then leak blood and fluid into the eye, leading to vision problems.

The researchers knewthey could halt and even reverse the condition by suppressing an overactive protein called vascular endothelial growth factor (VEGF). Other researchers had been able to do it with monthly eye injections, but this team was hoping to do it with just one injection.

The best way they found to do this was by using a common cold-like virus called AAV2 as a carrier of gene that activates the production of a differentprotein,sFLT01, tocounter VEGF.

In a preliminary trial involving 19 men and women 50 years old and above, the researchers injected the patients with a form of AAV2that was genetically engineered to penetrate retinal cells and deposit the gene. After the virus deposited the gene, the cells began secreting sFLT01 which bound to VEGF and prevented it from stimulating leakage and growth of abnormal blood vessels, explained a Johns Hopkins press release.

The clinical trial showed promising results, with the condition of four of the patients improving dramatically after just one viral injection. Two others saw some reduction in the fluid build up, and the treatment didnt produce any side effects in any patients. Even at the highest dose, the treatment was quite safe. We found there were almost no adverse reactions in our patients, said researcher Peter Campochiaro.

Of the patients that didnt respond, the researchers discovered that five naturally produced antibodies that would attack the AAV2 virus, rendering it unable to complete its gene depositing mission. They think these antibodies could be prevalent throughout the population, making it difficult to determine how effecting the treatment would actually be.

Nevertheless, this research is a step in the right direction, especially with AMD expected to affect almost 5.44 million people in the U.S. by 2050. This preliminary study is a small but promising step towards a new approach that will not only reduce doctor visits and the anxiety and discomfort associated with repeated injections in the eye, but may improve long-term outcomes, Campochiaro said.

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An Experimental Gene Therapy Uses Viruses to Stop Age-Related … – Futurism

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Gene therapy might someday help mend badly broken bones … – Health24

19 May 2017 Gene therapy might someday help mend badly broken bones This experimental method combines gene therapy, stem cells and ultrasound

Researchers have found that an experimental technique has healed large bone breaks in lab animals, researchers have found.

The technique is still far from becoming a reality, but, it repaired large bone gaps in the mini-pigs scientists studied. The hope, the researchers say, is to eventually help people with badly broken bones that won’t heal.

The results of the study were published in Science Translational Medicine.

When a bone sustains a simple fracture, it is usually able to self-repair with time (and a cast). However, severe fractures can leave large gaps in the bone that the self-healing process cannot bridge.

The aim of gene therapy

Health24 previously reported that the basic function of genes is to regulate the production of proteins required for the healthy working of cells. Thus, genetic defects manifest in either too little or too much of a protein being produced.

The aim of gene therapy is to replace the defective gene with a healthy one. The correct amount of proteins will be produced, and the disease will then be cured.

Geneticists are literally snipping defective pieces out of a strand of DNA with molecular scissors called CRISPR.

Bone grafting

Right now, the “gold standard” treatment for those fractures is bone grafting, said Dan Gazit, one of the senior researchers on the new study.

There, surgeons take bone tissue from elsewhere in the body or from a donor and use it to repair the damaged bone.

When bone grafting is done with a patient’s own tissue often taken from the pelvis that means additional surgery. And it can leave patients with prolonged pain and added risk of infection, Gazit said.

Newapproach

First, the researchers implanted a matrix of collagen a protein in bone into the gap between the two sides of a fractured bone.

That collagen then attracted the bone’s resident stem cells, and gave them a structure to settle into. Stem cells are early cells that develop into mature tissue, including bone.

Once those cells have populated the gap in the bone, the next step involves gene therapy. The researchers injected a mixture of “microbubbles” and genetic material for a bone-promoting protein, called BMP, into the injury site.

That spurred the stem cells to form new bone tissue, according to the report.

In this study, the tactic healed bone breaks in all of the lab animals the researchers treated, Gazit said. In untreated pigs, the breaks did not heal, the findings showed.

A sophisticated approach needed

“But there are problems with BMP,” said Dr Joseph Lane, an orthopaedic trauma surgeon at the Hospital for Special Surgery in New York City.

A central issue, he said, is that very high BMP doses may be needed, and side effects including infections and excess bone growth are common.

The new approach is “going in that direction”, said Lane, who was not involved in the research. The “beauty” of it, he said, is that it harnesses the bone-promoting effects of BMP in a more natural way.

A number of questions should be answered before human trials are done, according to Lane. For example, he said, future animal research should look at more complicated fractures. The bone injuries used in this study are relatively easy to heal, versus severe fractures, Lane said.

Read more:

6 lifestyle triggers for broken bones

Menopause before 40 carries higher risk of broken bones

Patients in Mpumalanga are going home with broken bones

People with recessive dystrophic epidermolysis bullosa aren’t able to produce a protein that binds the upper and lower levels of skin together, and at the slightest friction, these layers slide and create blisters.

Tereza is the CEO of the National Osteoporosis Foundation and worked as a Nursing Sister in the field of Osteoporosis for 18 years prior to her appointment with the Foundation. She used to be the Educational Officer for the Foundation and co-wrote the patient brochure on Osteoporosis. Read more

The information provided does not constitute a diagnosis of your condition. You should consult a medical practitioner or other appropriate health care professional for a physical exmanication, diagnosis and formal advice. Health24 and the expert accept no responsibility or liability for any damage or personal harm you may suffer resulting from making use of this content.

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Gene therapy might someday help mend badly broken bones … – Health24

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New gene therapy for vision loss is safe in humans, study suggests – Science Daily

New gene therapy for vision loss is safe in humans, study suggests
Science Daily
In a small and preliminary clinical trial, Johns Hopkins researchers and their collaborators have shown that an experimental gene therapy that uses viruses to introduce a therapeutic gene into the eye is safe and that it may be effective in preserving

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New gene therapy for vision loss is safe in humans, study suggests – Science Daily

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Scientists identify biomarkers to guide hormone therapy for prostate cancer – University of California

A test commonly used in breast cancer has been found to also identify which patients with aggressive prostate cancer will benefit from hormonal therapy, according to a study led by scientists at UC San Francisco and the University of Michigan.

While hormone therapy has been used successfully to treat many prostate cancer patients, until now, researchers have been unable to predict which patients would benefit from early initiation of this therapy following surgery. The study, conducted by a team of researchers at 11 medical centers nationwide and in Canada, demonstrates the first new way to select the best treatment for specific patients.

In the study, which appears today in the journalJAMA Oncology, the researchers divided prostate tumors into three subtypes based on genetic patterns. Their results reveal that starting hormone treatment after surgery prevents the spread of the tumor in only one of the three types, known as luminal B, a particularly aggressive form that affects about one-third of those with the disease.

Hormone therapy carries significant side effects, so knowing which patients are likely to benefit from it can focus treatment on the right patients at the appropriate time, while sparing the others of increased risk of fatigue, sexual dysfunction, osteoporosis, diabetes and other conditions.

If confirmed, patients with the luminal B subtype could be selected for early initiation of hormone therapy, which would allow for treatment intensification for patients most likely to benefit from it, saidFelix Feng, a radiation oncologist with UCSF Health and a senior author of the study.

Weve clearly shown that there are different molecular subtypes of prostate cancer and that a test widely used in breast cancer can also potentially be used to help individualize therapy for prostate cancer patients as well. said Feng,a UCSF associate professor of Radiation Oncology, Urology, and Medicine, who specializes in the treatment of high-risk, aggressive prostate cancers. He is also a member of the UCSF Helen Diller Family Comprehensive Cancer Center.

The hormone treatment is known as androgen-deprivation therapy, or ADT. Just as estrogen has been found to promote breast cancer growth, male sex hormones called androgens notably testosterone stimulate prostate cancer. As in breast cancer treatment, depriving cancer of the critical sex hormone can starve some prostate tumors.

The test, called PAM50, has been used for over a decade to identify which breast cancers are the best candidates for hormone treatment. But no such screen has been available for prostate cancer, Feng said. The new research shows that PAM50 can also distinguish between the three prostate cancer subtypes.

Ultimately, our goal is to find the right treatment for the right patient at the right time, said Feng. Using the PAM50 test may allow us to take the first step towards this goal, in the setting of hormone therapy for prostate cancer patients treated with surgery.

Fengs co-senior author on the research paper, Daniel Spratt, a radiation oncologist at the University of Michigan, commented on the potential of the biomarker to distinguish between the three prostate cancer subtypes: luminal B, luminal A and basal.

Prostate cancer has seen a recent surge of both investigational and commercially available prognostic biomarkers, Spratt said. Luminal and basal subtyping can be added to a very short list of predictive biomarkers in prostate cancer to truly personalize treatment for prostate cancer patients.

The retrospective study focused on 1,567 prostate cancer samples from high-risk patients who had undergone radical prostatectomy. The scientists identified the three distinct gene expression profiles that define the three cancer subtypes and confirmed the finding in another 6,300 prostate cancer samples.

They determined that luminal B disease was the most aggressive, with metastases recurring in about half of the patients over 10 years, compared to about one quarter of the patients with the luminal A or basal subtype.

They found that ADT treatments were more effective with luminal B tumors and may even have worsened prognosis in the other types of tumors a finding that would need to be confirmed with a prospective study and to firmly establish the biomarker finding as a diagnostic tool to guide treatment, said Feng.

Feng and Spratt will co-lead a large, National Cancer Institute-funded prospective clinical trial involving as many as a hundred clinical research sites, using the PAM50 assay to identify patients by their cancer subtype, and then randomly assign them to treatment with radiation and a placebo or radiation and hormone therapy treatment.

Our research published today, while very provocative, needs to be validated in this prospective study, the researchers said. Were hopeful that the biomarkers will prove to be a robust predictor of hormone treatment success, so we can increase survival of even the most aggressive cases and at the same time limit hormone treatment to those patients most likely to benefit from it.

In addition to Feng and Spratt, co-authors include first author Shuang G. Zhao, from the Department of Radiation Oncology, University of Michigan, as well as additional researchers from UCSF; the University of Michigan, Ann Arbor, Mich.; GenomeDx Biosciences, Inc., Vancouver, British Columbia; the University of Wisconsin, Madison; Thomas Jefferson University, Philadelphia, Penn.; Cedars-Sinai Medical Center, Los Angeles, Cal.; Cleveland Clinic, Cleveland, Ohio; University of British Columbia, Vancouver, BC; Mayo Clinic, Rochester, Minn.; Johns Hopkins Medical Institutions, Baltimore, Md.; Northwestern University, Chicago, Ill.; and Harvard Medical School, Cambridge, Mass. The full list of authors, institutional citations, and declared conflicts of interest can be found in the full paper.

Funding for the study was provided by the Prostate Cancer Foundation, Evans Foundation, V Foundation for Cancer Research, and A. Alfred Taubman Medical Research Institute.

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Scientists identify biomarkers to guide hormone therapy for prostate cancer – University of California

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When Your Doctor Prescribes A Vibrator – HuffPost

Doctors have been adding a new tool to the arsenal of how they restore the sex lives ofmenopausaland post-menopausal women: the humble vibrator.

With the onset of menopause, a decrease in the production of hormones causes vaginal tissue to get thinner and drier. Vaginal muscles can also atrophy, leading to painfulsex a problem for half of all menopausal and post-menopausal women, according to the National Institutes of Health.But the solution might be as simple as a vibrating piece of silicon.

Vibrators that are used internally stimulate pelvic blood flow, which increases vaginal moisture and boosts sexual response, all of which makes sex (with or without a partner) better. Like any muscle, the vagina is best kept healthy with regular exercise its the use it or lose it thing. Deterioration of this muscle becomes more common as middle-age or older women find themselves in situations where they arent sexually active anymore single, divorced, widowed or just not having regular sex with partners.

Therapeutically speaking, frequent vibrator use can prevent and ward off conditions such as painful vaginal dryness and atrophy. And yes, doctors are recommending their use with the caveat that since the vibrator industry isnt regulated, certain cautionary steps should be taken. (In brief:Keep anything you put inside your privates clean, and dont share your toys with friends.)

Dr. Barb DePree, whos been a gynecologist for about 30 years and was recognized by the North American Menopause Society in 2013 as the practitioner of the year for her exceptional contributions to menopause care, has long been prescribing vibrators to her patients. She keeps one handy in the exam room when she explains to her menopausal patients why regular vibrator use will be beneficial to their health, and suggests they try it.

While a few patients might have blushed through the years, all of them have been willing to take it for a spin, DePress told HuffPost. She explains that vibrators that stimulate just the clitoris might be fun, but for intercourse with a partner to resume pain-free, there must be pelvic floor activity.

One of her patients is a 70-year-old woman who reports having sex two or three times a week now without the use of lubricants or estrogen creams. She doesnt always achieve an orgasm, but according to her doctor, is quite pleased with what working with a vibrator for a few months accomplished.

DePree draws this analogy: When your vision started to fail, you didnt give up reading. You went out and bought yourself a pair of readers. Same thing is true about sex.

A survey of more than 2,000 women aged 18 to 60 indicated that 52 percent have used a vibrator.

Another benefit of vibrator use, said DePree, is they can help address the fact that orgasm intensity weakens with age. She said she commonly hears women say, Orgasm takes so much longer, and comes and goes so quickly its hardly worth it. She said, Those are the women who may benefit from introducing a vibrator too.

In a published paper she authored, DePree discussed a 52-year-old post-menopausal patient who sought her help. The woman estimated that at least five years had passed since she last experienced an orgasm. The patient had multiple sclerosis and was taking a selective serotonin reuptake inhibitor. She had tried a vibrator in the past, without success.

As a physician, I knew that she needed a more powerful motor for more intense stimulation. I was able to let her feel the difference and obtain the appropriate vibrator. Imagine her appreciation when she returned after achieving success, DePree said.

Having vibrators to road test in the safety of a doctors office also seems to be a boon. Not every woman feels comfortable going into a sex toy shop for the purchase. Online, the choices are mind-boggling. There are hundreds to choose form, and they can range in price from under $10 to the super-deluxe MotorBunny for $900 and the even higher priced Sybian.

Dr. Mary Jane Minkin, a Yale University obstetrician and gynecologist, brought vibrators out from under the bed a few years ago when she began prescribing them to Yale Cancer Clinics cancer patients, who often struggle with early menopause and need to combat its side effects. The vibrators increased her patients blood flow, and yes, improved their sex lives.

While the American Congress of Obstetricians and Gynecologists, the primary professional organization for ob-gyns, doesnt have an official policy on using vibrators to treat menopause and post-menopausal symptoms, a spokeswoman from the group told HuffPost that the organization doesnt really take issue with it.

And the organization does recommend masturbation to combat painful sex. I believe you could extrapolate that external stimulus, like a vibrator, fits into those categories, said Maggie McEvoy of the ACOG communications staff.

There are, of course, other options to help restore the vaginas elasticity and health for those who are unable or unwilling to go the vibrator route.

Hormone replacement therapy is controversial, but still on the table. Its use to treat symptoms of menopause changed abruptly after a large clinical trial in the U.K.found that the treatment actually posed more health risks, like breast cancer,than benefits for one type of hormone therapy.

But further review of clinical trials and new evidence show that hormone therapy may be a good choice for certain women, depending on their risk factors.Low-dose vaginal preparations of estrogen which come in cream, tablet or ring form can effectively treat vaginal symptoms and some urinary symptoms, while minimizing absorption into the body, says the Mayo Clinic.

There are also vaginal lasers, a relatively new FDA-approved treatment, that work by stimulating collagen production along vaginal walls, helping to build up the tissue again. The MonaLisa Touch and similar laser processes require three treatments (spaced a month apart) and cost about $3,000 that likely wont be covered by your insurance.

On the plus side, there have been18 studies that speak to the MonaLisa Touchs efficacy, all largely positive. One Stanford university study of 30 women found that all of them responded positively to the treatment. They showed highly statistically significant improvement in symptoms including dryness, pain, itching, painful urination and painful intercourse after the first treatment.

The North American Menopause Society gives the process a resounding maybe. It notes that the FDA approval process for devices is less strenuous than the one for new drugs, and these products havent survived the test of time yet. Meaning: They havent been around long enough to know the longer-term results.

The procedure itself doesnt hurt, but does require an annual maintenance treatment.You also shouldnt have laser therapy until youve had a Pap test and a thorough exam by your doctor to ensure that there are no other medical issues such as fibroids causing the pain.

Options are a good thing, right?

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When Your Doctor Prescribes A Vibrator – HuffPost

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What Is Metabolism? – Vogue.co.uk

Agnes LLOYD-PLATT

This isnt what I came for. Id walked into the acupuncture clinic close to my house – one of those mysterious places that lists ailments in the window to draw people in – in desperation with my painful shoulder, and a few minutes pulse-checking and tongue-inspecting later, I got this: Your metabolism is like a belligerent, ageing dog, unwilling to go for a walk. Im affronted, which seems to spur the Chinese-medicine therapist on: You are a tortoise when you should be a hare. Or at least a rabbit. Right. Im too polite to tell her to stop the animal metaphors, but Im concerned. I do feel sluggish, but then doesnt everyone? Or perhaps everyone doesnt feel like this and I am indeed a tortoise.

The word metabolism is bandied about all the time as women we decide the type of metabolism we have when were teenagers, and this notion sticks. Increasingly, though, its being seen as one of the pillars of preventative medicine – that current health buzz phrase. Its a major shift in perception for doctors and patients alike. Its vital to recognise the warning signs your body is giving you and act to prevent avoidable damage. You can outfox ageing, declares Dr Sara Gottfried, epigenetics expert and author of the New York Times bestseller The Hormone Cure, as well as a new book enticingly titled Younger. Certainly, it feels compelling to ease the gradient and speed of hormonal decline to protect heart and bone health and OK, I admit it, to stave off a middle-age spread rather than tackling it once it appears.

But it occurs to me that I still dont really know what metabolism actually means. The dictionary definition is uninspiring: The chemical processes within a living organism in order to maintain life. I mention it to my psychologist friend Nicole Sihera, who rings later that day. Well, its easier to blame metabolism than take responsibility for ourselves, isnt it? Its called a self-serving bias, she says. Of course, it does feel very unfair when you see someones Instagram account where they spring out of bed at 6am every day, citing the power of positivity and theres not a bloated stomach or podgy arm in sight. Its enough to make me reach for a pain au raisin and blame my metabolism, but I suspect theres more at play.

The fact is, I do feel lethargic in the mornings, even after a good nights sleep, and my weight has crept up by several kilos in the past few years despite no obvious change in my diet. I drink more alcohol than I used to and am probably not as active. My first thought is to have a full fitness analysis to get some truths. I decide to book in with head trainer and sports-medicine specialist Luke Worthington at the Third Space and make a mental note to be as transparent with him as I can.

I walk in to discover that Luke is an Adonis and I am immediately disinclined to reveal anything, especially not my suspected too-high body-fat percentage. I know youd like me to tell you that people can have a fast or a slow metabolism but that isnt the case, he says. The differences between our metabolic rates are marginal, to say the least. In fact, the number of calories we need is highly correlated with lean muscle mass. The higher the muscle mass, the higher the metabolic rate. This is why men can eat more. Its also a main factor in why we put on weight as we age, because our muscle mass declines. Well, that isnt the answer I wanted. I rail at him, giving him anecdote upon anecdote about the girl we all know who has Dairy Milk and lattes for breakfast but is a size eight. Luke listens patiently and says: The very best advice I can give you is to start weight-bearing exercise. The tipping point for muscle decline is 30. By 40 you start to see the visible physical effects unless you put in the work. The benefits to the body are numerous, not least an increased sense of energy and wellbeing.

I undergo a full scan, which enthusiastically spews out all kinds of stats about the state of my body. I am less than wowed. My magic personal metabolic rate is 1,424 calories, the number that my body would need to keep going each day if I just sat still. For comparison purposes, Luke tells me that his gym-bunny colleague, who is a similar age and height but has a higher lean muscle mass than me, has a personal base rate of 1,600. Theres a handful of nuts in it, calorifically speaking. Luke does crack and say there are other factors, which can be implicated in a feeling of sluggishness that we commonly call a slow metabolism, and I pounce on them, disliking myself for my desire for a quick fix. Thyroid function plays a role, as do insulin response and hormone profile, all of which can be affected by age. But if we eat well and exercise regularly, then much of this negative change is avoided, he explains. My next move, then, is to book in for blood tests to see if hormone function is at play.

Its no coincidence the majority of my patients are over 40 and report the same unhappy triumvirate: fatigue, a sluggish digestion and weight gain, says Dr Sohre, a GP-turned-private-wellness doctor from the Omniya clinic in London. The common factor is a changing hormone profile which can have a negative effect on our wellbeing and certainly influences our metabolism. Quite literally we start to feel less energetic. I undertake a sweep of tests to determine the state of my hormones. Testosterone, which women need to feel vital and maintain muscle mass, is often the first to fall, Sohre continues. I ask what metabolism means to her. For me, it means how healthy we feel and how well we process what we eat. Weve all had that heavy feeling after a meal that, for some, can last for days. I believe improving gut health, optimising hormone levels before the crisis of menopause and eating a healthy diet is the key to getting our metabolic processes firing on all cylinders.

While I wait for the results, I throw myself into some gym visits. I spend time on the weight machines because Luke Worthington and Dr Sohre were both unequivocal: muscle equals metabolic oomph. I tell myself Ill reap the rewards of the afterburn the brilliantly fizzy metabolic term for the two-hour period after exercise when the metabolic rate is proven to increase two- to threefold. Exercise increases metabolism, says Dr Thomas Barber, an obesity researcher and associate professor of clinical endocrinology at the University of Warwick, but it doesnt have to be strenuous. Just by walking about, youre boosting your metabolism and improving health. Weve found that the process of simply contracting a muscle releases beneficial hormone signals called myokines, he explains.

Results day, and Dr Sohre draws a circle on a piece of paper, placing the words thyroid, cortisol, insulin, female hormones around the outside. Each of these will impact your wellbeing and all are mutually dependent. So, for example, a waning thyroid will drain the bodys progesterone production, and a body pumping out the stress hormone cortisol will drain the thyroid, she explains. Results bands for blood tests are typically quite broad. If you were being assessed in the NHS, you would be told you are OK. Theres a pause. But Im looking for optimum health and all of your results are in the bottom third of these reference bands. Your thyroid function isnt clinically abnormal but with levels like this at your age I would expect you to feel the cold more than most, accumulate fat on your tummy and be fatigued. Yes, yes and yes. Your results are clearly sub-optimum and only headed in one direction without intervention. Im starting to feel that the grim reaper will lurch out of the supplies cupboard. No one wants the blood results of a septuagenarian, not even a septuagenarian.

Dr Sohre lifts the mood with her can-do attitude and a plan of action that includes a high-strength thyroid-support supplement, which I am to take as religiously as a medicine to see if we can pep it up without recourse to a prescription for something stronger. A well-functioning thyroid means feeling rested on waking, an efficient digestion and the body basically running more sparkily. I resist knocking back the whole bottle right there at her desk. Im also dispensed a bio-identical progesterone hormone to top up my waning supplies to balance my oestrogen, which she promises will make me feel less grumpy, less puffy and more energetic. Lastly, I am prescribed DHEA to bolster my below-average results. Its the mother hormone made in the adrenal glands. It manages the metabolic processes in the body and cascades to make lots of other hormones, and dwindles with age. By 70 we make around 20 per cent of what we make in our twenties, explains Dr Sohre. DHEA production is also hampered by stress because the body diverts attention to pumping out cortisol, so the stressed-out middle aged are hardest hit. DHEA is considered by many to be a panacea for all ageing ills and is available over the counter in many countries but not in Britain. I realise I am clutching the bottle like Gollum with his ring.

I leave Omniya feeling optimistic, reflecting on the decision Ive made to take medication to optimise my wellbeing rather than treat illness. Its quite clear that metabolism is more than just a weight-gain/weight-loss stooge. Its a catch-all for all the biochemical reactions happening in the body and the trick is to set the conditions to help it flourish. So dont question whether yours is fast or slow, ask instead: is it functioning well?

The fast lane Your thyroid is the main driver of your metabolism. Look after it. Natures Plus Ageloss Thyroid Support, 31 for a months supply, at Amazon.co.uk or Omniya.co.uk

Listen to your body If youve slowed down, think about a body MOT with a preventative medicine specialist. Metabolism & Energy consultation with Dr Sohre at Omniya (3a Montpelier Street, SW7), 250

Help your body burn energy efficiently Healthy gut flora have been proven to support metabolic processes from insulin sensitivity to the livers ability to metabolise fat, explains nutritional therapist Kerry Beeson. Optibac Probiotics Extra Strength, 22.99, Optibacprobiotics.co.uk

Cooling the body induces a metabolic kick The latest fad is to lock yourself in a cryo chamber at -90C to burn calories, heal injuries, pump up the endorphins and give your body a turbo boost. I left bouncing around like a teenager. 95 per session, at 111cryo.com

Metabolism is like moving a boulder Getting started is the tricky part, then momentum takes over. For impetus, drink strong green tea, which has thermogenic properties, and take a mood-enlivening supplement: try Higher Nature Drive (18.30, Victoriahealth.com) which provides the co-factors for energy, balanced brain chemistry and get up and go.

Continue reading here:
What Is Metabolism? – Vogue.co.uk

Recommendation and review posted by sam

Hormone therapy aygestin – Aygestin therapy – Aygestin abdominal pain – The Independent News


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Hormone therapy aygestin – Aygestin therapy – Aygestin abdominal pain
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Hormone therapy aygestin – Aygestin therapy – Aygestin abdominal pain – The Independent News

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