The international group of scientists knew they were setting out to investigate an explosive subject: the hereditary basis of human same-sex behavior. Even so, the members of the prestigious Broad Institute in Cambridge, Massachusetts, may not have anticipated the magnitude of the public furor that erupted when they published their study, which identified several markers in certain genetic loci in the human genome related to same-sex sexual experience. The storm of reactions ranged from those who welcomed something seen as heralding significant progress in the field, to others who maintained that it would have been better if the scientists hadnt published anything.

The research results were published in full in the journal Science, at the end of August. This was the most extensive study of its kind ever conducted (there were about a half a million subjects), in which use was made of the GWAS (genome-wide association studies) method to analyze genetic big data. The researchers discovered five genetic markers (frequent, minor changes in the DNA segments of certain chromosomes) that appeared repeatedly among individuals who reported having had same-sex sexual experiences. Slight and frequent genetic variations were identified in both women and men, two others in men only and one more only in women.

No less important in the study, entitled Large-scale GWAS reveals insights into the genetic architecture of same-sex sexual behavior, is the scientists claim that a large number of genetic markers, perhaps even thousands, might operate simultaneously together although each in and of itself is of minuscule weight and influence ones same-sex orientation. Moreover, their study led the researchers to the conclusion that human genetics can explain up to 32 percent of same-sex sexual behavior.

What is at issue here, however, is not what the study contains but what it does not contain. As Melinda Mills, a sociology professor at Oxford, writes in the same issue of Science, there is no way that the researchers findings can be used as a tool to accurately predict same-sex behavior. Specifically, the fact that genetics can explain up to 32 percent of the fact that someone is gay or lesbian, does not mean that sexual identity is determined primarily by environmental factors not to mention social ones. This story is far more complex and has not yet been fully deciphered. Mills views are shared by Andrea Ganna, one of the chief authors of the new study.

What we basically do is statistical associations between having and not having these genetic markers and having or not having same-sex behavior, Ganna told Haaretz in a phone interview. Because we had this uniquely large study, he continued, which allowed us to have robust conclusions, and because we had the technology to measure the genetic markers of so many individuals, the time was right to confirm something that we expected: There is no one specific gay gene. Instead there are a lot of relatively common genetic markers, genetic mutations, that have a small effect on same-sex behavior.

At the same time, adds Ganna, a geneticist at Harvard Medical School and at Finlands Institute of Molecular Medicine, Not everyone is interpreting the fact that theres no single gay gene in the right way.

Gannas concern is shared by scientists around the world. Theyre worried that the researchers findings will fuel prejudice and discrimination against the LGBTQ community, and even spark calls for genetic engineering and genetic diagnosis among its members. So serious are these apprehensions that some have wondered whether the study would not do more harm than good.

As a queer person and a geneticist, I struggle to understand the motivations behind a genome-wide association study for non-heterosexual behavior, Joseph Vitti, a postdoctoral researcher at the Broad Institute, wrote on its blog, adding, I have yet to see a compelling argument that the potential benefits of this study outweigh its potential harms [T]he results presented not only oversimplify the question of biological causality, but also threaten direct damage by perpetuating the stereotype of LGBTQIA+ people as imprudent, while also likening same-sex attraction to a medical or psychological disorder.

Moreover, a website called The American Conservative posted an article entitled Not Born This Way After All? which wondered, skeptically: If the study proves that homosexuality is related to the environment, above all, and not to heredity why isnt it right and proper, in scientific terms, to allow those who so desire to undergo treatment in order to reduce their same-sex desires, which have now been shown not to be genetic?

That, however, is a simplistic reading of the studys findings. According to Michael Bailey, a professor of psychology at Northwestern University in Illinois, who was not involved in the study but has been conducting research on sexual orientation for 30 years, Its very important to understand that environment does not simply refer to social surroundings, like what your parents teach you and what kids you know, trauma and so on theres also a biological environment that begins right after conception.

Three years ago, Bailey and several colleagues published a survey of all the studies and professional literature in the field. The best studies have shown that genes are probably important but not overwhelmingly important, he tells Haaretz. We estimated in our 2016 review that 30 percent of the variation in sexual orientation is due to genetic variations. It may be this finding that led him to conclude that it is the biological environment that is mostly important. Bailey is convinced that men are born with their sexual orientation and that it is not subsequently acquired at any stage. He notes that there are several cases, I think there are seven throughout the professional literature, in which a baby boy was changed into a girl for medical reasons and was raised as a girl. When you follow these individuals through adulthood, you find that they are attracted to women and not to men.

In Baileys view, the best example of how biological-environmental factors can influence sexual orientation is the fraternal birth order effect. The phenomenon, whose existence is well established, he says, shows that the more older brothers a man has, the more likely he is to be homosexual. In practice, every older biological brother increases the probability that the youngest brother will be gay by about 33 percent. Thus, if the probability that a man with no older brothers will be gay is 2 percent, one older brother will increase the probability to 2.6 percent, and a second, third and fourth brother to 3.5 percent, 4.6 percent and 6 percent, respectively. Whats not yet clear is the reason for this.

In my mind, Bailey suggests, the best hypothesis as to why this happens is that a mothers immune system becomes increasingly active and produces antibodies against male proteins over successive births.

Fingers and hands

Behind this hypothesis is one of the most influential figures in the field, American-Canadian clinical psychologist and sexologist Ray Milton Blanchard. He was also among those who linked the fraternal birth order effect to another phenomenon of interest to scientists: the connection between being left-handed and having a same-sex orientation. The most extensive study in this regard was conducted in 2000, incorporating 20 different studies involving 7,000 gay male and female subjects and 16,000 heterosexual ones. It was found that gay men were 34 percent more likely to be left-handed. The situation was more extreme among lesbians: They were seen to have a 91 percent greater chance than straight women of writing with their left hand.

As a result, six years later, a research team led by Blanchard argued that the fraternal birth-order effect is relevant only among right-handed men. The reason is that, in any case, left-handed men who dont have older brothers already have a greater likelihood of being gay than right-handed men with such siblings.

A persons dominant hand turns out to be significant in another sense as well. An article published two years ago (about a study in which all the subjects had taken part in a gay pride parade in Toronto) found a connection between that hand and the gay persons role in bed: that is, the proportion of left-handed gays who defined their sexual behavior as passive or versatile (i.e., sometimes passive, sometimes not) was significantly higher than among those who described themselves as actives who clearly tended to be right-handed.

In research conducted over the years on the subject of the connection between sexual orientation and other attributes of the body, the hand holds a place of honor. But while Blanchard developed his theory on the basis of the whole hand, sometimes a few fingers are also enough: two, to be exact. In his 1998 study, British biologist John Manning confirmed a relatively old hypothesis, first put forward in Germany almost 150 years ago. Its gist is that the proportion between the length of index and ring fingers is, typically, different in men and women. Manning found that this phenomenon was detectable as early as age 2, which led to the observation that its source lies in the differences in testosterone and estrogen levels that already exist in the womb hereinafter: a biological-environmental factor.

Manning did not emphasize the element of sexual orientation in the two books and over 60 articles he wrote on this subject, but in the two decades that have elapsed since his study, more than 1,400 papers have been written on the ratio between the length of the second and fourth fingers (known as 2D:4D) and the connection between it and the level of risk of contracting certain diseases, as well as personality traits, cognitive and athletic abilities and sexual orientation.

One such study, published in 2010, maintained that straight and lesbian women are differentiated by the ratio between the length of the index and ring fingers, with lesbians tending to show a more masculine ratio i.e., closer to the average difference between the length of the fingers, among men. However, no such differences were found between gay and straight men.

Last year a team of scientists led by a British psychologist measured the fingers of 18 pairs of identical female twins, one lesbian, the other straight. Overall, differences in proportion were documented only in the lesbians and only in their left hand, and were comparable to the situation among men. This fact, the team concluded, could indicate a heightened exposure to testosterone in the womb but their study was based on a very small sample and drew much criticism. The critics charged that the conclusion was based on an overly simple means of measurement: of the way only two variables impacted each other. And, they added to bolster their argument, findings of studies involving those fingers have not been replicated in scientific experiments.

The field of gay science has been on a roll in recent years, but has a far longer history. Its modern phase dates to the early 1990s, when scientists began to publish increasing numbers of studies arguing that sexual orientation has a biological component. A leading scientist in this field is British-American neurobiologist Simon LeVay, who in 1990 performed autopsies on the bodies of 41 people: 19 gay men, 16 straight men and nine women. He discovered that the brain cells known as INAH-3 among the deceased gay men were relatively small, and closer in size to those of women than to heterosexual males.

In 1991, LeVay told Haaretz in a phone conversation, I published a study that got a lot of media attention, related to my observation that there was a region inside the hypothalamus that was different in size between men and women, and also between gay and straight men My additional finding was the difference in size between gay and straight men in this region inside the hypothalamus that is involved in the regulation of sexual behavior.

Adds LeVay, My general feeling is that there are certainly strong biological influences on peoples sexual orientation, but we cant say everything is genetic.

In the spirit of the period, and in light of the AIDS epidemic at the time, LeVay tried to be as cautious as possible about his conclusions. Its important to stress what I didnt find, he said in an interview to Discover magazine, in 1994. I did not prove that homosexuality is genetic, or find a genetic cause for being gay. I didnt show that gay men are born that way, [which is] the most common mistake people make in interpreting my work.

Three decades after publishing his study, he still thinks media coverage is doing an injustice to research even if its not his. Ive seen some headlines saying, basically, that this study [i.e., that of Ganna and his associates] shows its not genetic, or that are no gay genes, or something like that; and, of course, its not what the study shows at all.

Truly gay

In recent decades, scientific research (on men and women alike) in this realm has relied on an additional field: molecular genetics. The pioneer is geneticist Dean Hamer, who in 1993 conducted the first study of its kind.

We noticed that being gay, for males, tended to pass down through the mothers side of the family, he told Haaretz. And that is characteristic in genetics of something on the X chromosome because males get their X chromosomes from their moms That led us to look in families where there were gay brothers, to see if they shared anything on the X chromosome.

And thus, recalls Hamer, he and his team discovered Xq28: a genetic marker that plays a part in determining whether a person will be heterosexual or gay. He emphasizes that this is a factor, its not the factor and actually, overall, its not even the most important factor. He adds, Whats good about genetic studies, is that you know that whatever you find is a causal factor, because of course people are born with their genes, and its not something that changes over time.

LeVay, he explains, is looking directly at the brain, and were looking at what we think is building the brain and genes. Yet, its very difficult to know whether one was born with a brain like that, or whether that brain developed that way because of your behavior the causality is rather unknown.

At the same time, Hamer adds, That doesnt mean there arent specific pathways, because there has to be some sort of a pathway in the brain that controls sexual orientation. We know, for example, that the reason you become a male or a female is very simple: If you have a certain gene on the Y chromosome, you will produce male hormones, and if you have those you make a penis and scrotum and you become male. Accordingly, Theres probably some pathway in the brain that does same thing for sexual orientation, but were not going to discover it from genetics The answer will probably emerge from some sort of very sophisticated brain and developmental studies.

For 35 years, Hamer accumulated experience as a scientist at the National Institutes of Health in Bethesda, Maryland. That period is behind him. He doffed the white coat and now lives in Hawaii, where he makes films. But even if hes no longer occupied with research, it still occupies him.

Hamer: Back in the 1990s, I, along with all the scientists involved, believed that if we did good genetic studies wed find the important genes. For example, well find a gene that is responsible for the production of testosterone, and if its functioning was low, it would be possible to say that this is the cause of homosexuality in a particular person. But it turns out that it doesnt work that way. For every mental trait that has been studied everything you can imagine in the brain, for every single trait, theres a [vast number of] genes not to mention a host of complex societal and environmental factors.

For his part, Hamer has much praise for the Broad Institute study: The new GWAS study is really important, because for the very first time they used a huge sample and they mapped every inch of the genome. And this has never been done before. All the other studies were much smaller, or used many fewer genetic markers. But he also demurs: Whats very important is to look at what they actually analyzed. They didnt analyze people who were gay or lesbian, but anyone who had one single same-sex experience, which is quite different... They were measuring something more like openness to sexual experimentation.

As Hamer sees it, If you look for those five markers, or even just the three strongest markers, they are not necessarily found in people who actually identify as gay or lesbian. If you take people who are gay, like me, and look for those markers theyre not significantly there.

Hamer thinks that the whole field is lagging behind because of insufficient research, owing to the stigmas that plague the subject. I dont think sexuality is any more complicated than many other areas of human personality and individual differences, he observes, noting, We formally established that male sexuality is something that is deeply ingrained in people, its not any sort of choice really. It starts really early in life, and it has a major biological component to it. But, how it works? What the biological component is? Were completely unaware and dont know anything, and we barely know more than we did 25 years ago, or in the 1940s, when Kinsey did his work, to be honest.

Hamer was referring to biologist Alfred Kinsey, who in 1948 stunned the American public with his book, Sexual Behavior in the Human Male, which addressed previously taboo subjects, and challenged the traditional beliefs and existing knowledge about human sexuality. Kinsey had conducted a survey of men, which found that 37 percent of his subjects said they had undergone a homosexual experience of some kind, and 10 percent said they had been exclusively gay for three years of their adult life a statistic which to this day is generally said to represent the proportion of people engaging in same-sex behavior.

At the same time, subsequent studies reveal that the percentage of people who define themselves as exclusively homosexual is far lower, though it fluctuates from one article to the next. For example, a 2011 survey of nine different studies on the subject revealed that approximately 3.5 percent of Americans identify themselves as gays, lesbians or bisexuals. A poll involving 1,000 Jewish Israelis in 2012 found that 11.3 percent of the male respondents and 15.2 percent of the female ones said they felt an attraction to members of the same sex. However, only 8.2 percent of the men categorized themselves as gay or bisexual, while 4.8 percent of the women said they were lesbian or bisexual.

For his part, Ganna, of the Broad Institute, understands some of the criticism of his research. What we studied is not related directly to the biology, but to extended environmental factors related to it. Its not about our sample size once you have a lot of individuals, you can capture very small effects. But are these directly influencing same-sex behavior, or other things related to this topic? As a medical example, think about a study that looks for associations between genetic markers and lung cancer. In that example, what we found are genetic variants regarding how much you smoke, which is related to lung cancer.

One of the lessons, and one of the most interesting points arising from the study has to do, says Ganna, with the mode of measurement that had been in use since 1948, when Kinseys scale ranked individuals as being between 0 (totally heterosexual) and 6 (totally homosexual).

Ganna: Basically, the tendency is to locate individuals on a continuum. You can supposedly be anywhere between 100 percent heterosexual to 100 percent homosexual, which implies that the more youre homosexual, the less youre heterosexual, and vice versa. We show that this assumption actually doesnt hold water: When we look at the genetic data, its not that straightforward, theres no simple continuum of sexuality.

So, actually, you are refuting the Kinsey scale?

Ganna: Thats exactly one of our conclusions. What were now doing is, rather than asking people to put themselves on a scale somewhere between being exclusively heterosexual or exclusively homosexual, we ask them how much theyre attracted to men and women. You could be attracted to either of them, very attracted to both of them or to one more than the other. And that information will be crossmatched with genetic markers.

In the final analysis, he adds, We showed that this is just another natural human variation. Sexual orientation, similar to many other behavioral traits, is complicated and is composed of different factors. The interesting thing is how genetics and environment work together. If you think about how much more prevalent same-sex behavior has become lately, people engage in it more than in the past. And thats clearly not because our genetics are changing. Its because of the environment, because society is becoming more open and laws are changing.

Further research should focus on the relationship between environmental factors and genetics, Ganna says, and on how they interact. Its somewhat misleading to think of nature and nurture as separate aspects; they both contribute. So, it would be wrong to say that you can use only DNA to predict if someone will engage in same-sex behavior, but you also cant say its simply a [matter of] choice.

In summary, he says, I think that the more people who will understand that there are genetic and environmental components to sexual behavior, the better and this is a message that goes beyond just sexuality.

Choice and lifestyle

However, the relationship between science and the environment, and particularly the people living in it, is a complicated one. The subject definitely should be studied, but the social aspect of it is problematic, says LeVay, the neurobiologist. I am gay myself, and I feel strongly that gay people should be valued and accepted into society, regardless of what caused their sexual orientation. I dont think its vital for gay liberation to prove that gay people cant help but be gay there are plenty of other reasons [for accepting them], including basic human rights.

At the same time, he adds, this issue is socially relevant, because of traditional notions that see same-sex relations as a choice, a lifestyle or sinful behavior.

In recent years, there have been many studies showing that peoples attitudes toward homosexuality are closely tied to their beliefs about what makes people gay, says LeVay, citing a survey that showed there was a high probability that people who think homosexuality is a choice will object to a gay person being their childrens teacher which in a way might make sense, he adds: If you think being gay is something infectious, socially contagious, and you didnt want your kid to be gay, then you wouldnt want their teacher to be gay ... It follows that demonstrating that biological factors are involved, helps counter those ideas. Still, Im a bit ambivalent about the use of this type of research as some sort of a political weapon in the struggle for gay rights.

The Broad Institute study contains a reminder of the problems and stigmas that still exist with regard to the LGBTQ community. One of the parameters it considers are genetic correlations between genes that are ascribed to homosexuality, and certain psychological problems.

Bailey, the psychologist: One thing that was perceived as controversial, was to look for and find a genetic overlap between homosexual sex genes and genes associated with depression. Its not the same as saying all people who engage in homosexual sex are depressed for genetic reasons, but its also not something that can be easily ignored. There are assumptions that the higher rates of depression among gay men and lesbians is due to the way they are mistreated by society, but the evidence for that is not so overwhelming. There is also the fact, for example, that you have as high a rate of depression among homosexual men in the Netherlands, which is very tolerant, as you have in some less tolerant places, like the United States.

Ganna, for his part, tries to soften that criticism: Even if we see genetic overlap, or correlation, it is not set in stone that weve found a biological mechanism that causes depression and same-sex behavior, he says. There are many explanations for why this one genetic marker is associated with both things. But finding these correlations help us study human traits in general.

In the meantime, there is a price to be paid for conducting research in this realm, which all those involved must be aware of. Reminders of this abound, and are almost routine. In some cases whats at stake is not even a groundbreaking study or one of tremendous scientific importance. In 2017, for example, two researchers from Stanford published an article stating that gay men are predicted to have smaller jaws and chins, slimmer eyebrows, longer noses, and larger foreheads; the opposite should be true for lesbians. In the next stage, they created a facial-recognition program with the aid of more than 14,000 images taken from a singles site of straights and LGBTQs. The program was able to distinguish between gays and lesbians and heterosexuals with an accuracy of 81 percent for men and 71 percent for women, in contrast to an average rate of successful human guesses of 61 percent and 54 percent, respectively. Even though the program achieved relatively impressive results, the study as such drew widespread criticism not unusual for researchers engaged in such studies.

The Stanford gays identification program may be an extreme example, in this respect, but its also a byproduct of the considerable surge in studies in this field, a trend that began in the early 1990s. Together with the scientific community, media interest in the subject of same-sex orientation and its causes has contributed substantially to transmitting messages and shaping public opinion.

In the United States, this can be seen in a series of polls conducted by Gallup, Inc. The first one, conducted in 1977, found that only 13 percent of the respondents believed that homosexuality is an innate tendency, while 56 percent attributed it to environmental factors. This approach remained largely constant until the period between 1989 and 1996, when the rate of those supporting the innate thesis leaped from 19 percent to 31 percent; by 2001, it stood at 40 percent. Almost a decade and a half later, the annual poll produced, for the first time, a larger proportion who agreed with the innate argument. The latest survey, from the end of last year, showed this trend continuing: More than half of the American public believes that gay people are born with their sexual orientation, whereas only 30 percent attribute it to environmental factors (10 percent said both factors play a part, 4 percent cited other factors and 6 percent said they werent sure).

Changes in the perceptions of the origins of sexual orientation are having a pronounced effect on the struggle LGBTQ individuals are waging for equal rights. The latest Gallup poll shows that an absolutely majority (88 percent) of those who believe that homosexuality is an innate trait also support legitimizing same-sex marriages. In contrast, most of those who see this orientation as being environmentally driven (61 percent) are against.

When it comes to public opinion, which is very important, the born this way idea has been really resonant and has had a very positive impact on society, Hamer maintains. Public opinion polls asked people whether they think [gays] were born this way or not, and we know that believing that homosexuality is innate correlates with having positive feelings toward gay rights. Overall, its been important in educating the public about who we are, as gay people.

Such messages are reaching Israel as well. A poll conducted by the Dialog Institute for Haaretz at the end of 2013 found that 70 percent of those questioned favored full rights for same-sex couples, while 64 percent specifically backed their right to surrogacy. However, two polls conducted in the wake of the surrogacy law protest in July 2018 presented slightly lower numbers: About 57 percent of respondents expressed support for the right of same-sex male couples to surrogacy.

These polls did not ask Israelis whether they believe the origin of same-sex orientation is innate or environmental. If you ask Bailey, though, that doesnt really matter.

Ive gone to great lengths to try to persuade people not to base equal rights for gay people on the causal hypothesis, he says. Its a terrible idea to say gay people should have equal rights because they were born that way. Its terrible in part because some criminals might be born that way, and you dont want to them to have the same rights. Being gay doesnt harm anybody, other than people who are close-minded and easily offended. Preventing people from expressing their homosexuality is quite destructive for them. Thats true whether gay people are born that way or not.

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Is sexual orientation genetic? Yes and no, an extensive study finds - Haaretz

Could one woman's rare genetic mutation one day have a global impact on dementia risk?

It's possible, say investigators who report on a potentially groundbreaking case of a woman whose genetic mutation staved off dementia for decades, even though her brain hadalreadybeen damaged by Alzheimer's disease.

While most Alzheimer's cases are not driven by genetic predisposition, one woman in Colombia is among about 1,200 in her country who do face a genetically higher risk for early-onset Alzheimer's.

Why? They all carry the E280A mutation of a gene called Presenilin 1 (PSEN1), which is known to increase the chances for Alzheimer's at a far younger age than usual.

"We identified an individual that was predisposed to develop Alzheimer's in her 40s," noted study author Dr. Joseph Arboleda-Velasquez. He's an assistant professor of ophthalmology with the Schepens Eye Research Institute of Mass Eye and Ear at Harvard Medical School, in Boston.

But, strangely, the woman "remained unimpaired until her 70s," Arboleda-Velasquez added.

The twist: the woman had, in fact, developed clear telltale signs of Alzheimer's in her brain. She just hadn't developed dementia.

For example, while she had fewer neural "tangles" in her brain than is typical for Alzheimer's patients, by the time she hit her 40s she did have the same unusually high level of brain amyloid-beta deposits as her E280A peers. Such deposits are a key signature of Alzheimer's.

So why didn't she develop middle-aged dementia like her peers?

To unravel the mystery, Arboleda-Velasquez and his colleagues ran an in-depth genetic analysis on the woman. And what they found is that she had not just one mutation, but two.

In addition to the E280A mutation, she also carried the so-called "Christchurch" mutation in the APOE3 gene.

But there's more. Not only did she carry the Christchurch mutation, but she hadtwoof them. Some of her E280A peers (about 6%) also carried a single copy of Christchurch. But she was the only one who carried two, the investigators found.

"It is ultra-rare, with an approximate prevalence of less than one in every 200,000 individuals," Arboleda-Velasquez said.

And having one such rare mutation did not appear to be enough. No protection against dementia was linked to only one Christchurch mutation. But as this woman's case suggests, having two such mutations did seem to throw up a shield against Alzheimer's, preserving her ability to remember things and think clearly for a few decades, long after her E280A peers had started experiencing cognitive decline.

"This is the first time a specific patient who carries the [double] mutation has been linked to such a protective benefit," Arboleda-Velasquez noted.

How does it work? It seems that "the mutation puts a block on the cascade of events linking amyloid accumulation to neural [brain cell] death," he explained.

The team did acknowledge that more research will be needed to definitively confirm the Christchurch mutation's impact, and to further explore how this mutation/dementia delay connection truly works.

But, in theory, the incredibly rare experience of this one woman in Colombia could ultimately have profound ramifications for Alzheimer's patients around the world, if "new drugs that mimic the effect of [the] mutation" could be developed, said Arboleda-Velasquez. Rather than stopping Alzheimer's from developing, such drugs would prevent Alzheimer's from causing dementia.

The study was published Nov. 4 in the journalNature Medicine, and was partly funded by the U.S. National Institutes of Health and the Alzheimer's Association.

Heather Snyder, vice president of medical and scientific relations at the Alzheimer's Association, characterized the findings as "an important discovery."

The insights gleaned from a look at this particular patient's experience are "full of possibilities for increasing our understanding of Alzheimer's disease and all dementia, and advancing potential avenues for treatment," Snyder suggested.

"Understanding what is happening in the brains of people when there appears to be a delay or stopping of the disease progression because of this gene form or otherwise gives rise to many possibilities for investigating new treatment and risk-reduction opportunities," she added.

At the same time, Snyder cautioned that "more research is needed to understand more thoroughly how genetics impacts Alzheimer's/dementia risk, and to expand and confirm these findings in a larger number of people."

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Alzheimer's disease: Rare genetic mutation might hold clues to preventing or treating dementia - CBS News

Raleigh, N.C. Many people spend years searching for a diagnosis of a debilitating medical problem, paying for treatments or surgery that don't help. Now, researchers at UNC say that, for some, recent advances in genetic testing could fix their problems once and for all.

Elizabeth Davis, a local genes study participant, does not take walking for granted. For 30 years, she could barely walk at all. "When I was 6, I started walking on my toes," she said. "I started going to different doctors, trying to find out what it was."

The muscles in Davis' foot had tightened up, causing her pain. She needed crutches and, sometimes, a wheelchair. For years, the cause of her condition remained a mystery.

According to Dr. James Evans, a researcher at UNC's Center for Genetic Medicine, about 30 percent of patients find an answer to their problems when they participate in a genes study. Participants' blood samples are analyzed with the latest advances in DNA sequencing.

"The patients themselves typically seek us out because they've been looking for answers for a long time," said Evans. "There might not be a known treatment, so sometimes that answer doesn't really change their life significantly."

Davis saw positive results after participating in the study, and Dr. Jonathan Berg, an Assistant Professor of Genetics at UNC, was happy with the results. "Her case is an unusual one in that it just happened to be a condition that is exquisitely treatable -- with just a pill," said Berg.

The genes study discovered that Davis had a muscle rigidity problem similar to that of many people with Parkinson's Disease. Doctors learned that it was Dopa, a drug used by millions of Americans with the disease, could help Davis walk again.

"The relief was fast and just by taking a quarter of a pill," said Davis. "I overheard my oldest son telling his friend that 'his mom is not on crutches anymore.' I'll never forget him saying that."

The study, funded by the National Institutes of Health, has even bigger plans for the future. UNC researchers say they're planning a randomized controlled trial to see if these types of genetic tests can benefit patients in the long run and prove to be a cost-effective diagnostic test.

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In pain? For some, gene studies could provide a quick cure - WRAL.com

Each year, some 30,000 patients undergo transplant surgery to receive an organ from a donor. Transplant medicine saves lives, but not enough people are willing to donate. Patients cant rely on the generosity of fellow humans to replace a heart, kidney or lungs. According to the United Network for Organ Sharing (UNOS), one patient is added to the U.S. transplant waiting list every 10 minutes, and 20 people on the national list die each day.

For decades, scientists have been hoping to address the organ shortage in more innovative ways, namely by tweaking the innards of other mammals to make them compatible with humans. Successfulanimal-to-human transplants (also known as xenotransplantation) would create a sustainable organ supply.

Pigs are the strongest contender for xenotransplantation because they have organs similar in size and physiological function to those found in humans. But pig organs on their own arent suitable for transplant. Human immune systems would most definitely reject pig organs. But an even greater challenge is the risk of animal viruses infectinghumans. Pigs carry active porcine endogenous retrovirus, and it remains unclear whether these viruses could becommunicable or fatal in humans. PERV infection would be dangerous becausetransplant recipients are routinely put on immunosuppressant drugs that make it difficult to fight off any bacteria or viruses.

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If animal-to-human transplants can be achieved successfully, it would create a sustainable organ supply. Thanks to gene editing, this may be possible in the future. REUTERS

Nowa team of researchers affiliated with Harvard Medical School appear to have solved one of these problems. Not only have these scientistsmade a controversial possibilityanimal organs in humansmore likely, but theyve done so using a controversial technology: CRISPR-Cas9 gene editing.

Through gene editing, the team eliminated all traces of the PERV virus from the cell line and conducted in vitro fertilization. There are 25 strains of PERV, which is the only known active retrovirus found in pigs. In the study, published Thursday in the journal Science, biologist Luhan Yang and her team implanted the PERV-free embryos into surrogates. The fetuses did not become reinfected with the virus, and the newbornpiglets are the first animals born without PERV. Yangwho founded eGenesis a few years ago to harness advances in CRISPR-Cas9 for the worldwide organ shortagewill now monitor the animals for any long-term effects.

Im a strong believer that science can help us improve health care if we look holistically for a solution, says Yang, lead author on the paper and chief science officer of eGenesis, the biotechnology company funding advancements in the research. Because there are millions of patients who suffer from end-stage organ failure, their life could potentially be saved, or largely improved, by this potential organ resource.

CRISPR-Cas9, or CRISPR (pronounced crisper) for short, is an experimental biomedical technique. The technology utilizes snippets of certain bacteria that allow for selective modifications of DNA segments, such as changingthe misspellings of a gene that contributeto mutations. Since CRISPR was identified several years ago, scientists have been using it in the laboratory to alter the genetic codes of living organisms. The new technologyis already leading advances once considered the stuff of science fiction. In astudy published last week in Nature,scientistseliminated a genetic abnormality in a human embryo.

Yang has been determined tousegene editing to solve the organ shortage problemfor several years. In 2013, sheand her team published the first paper showing CRISPR could be used to accurately and effectively alter the immune system. In 2015, she eradicated 62 copies of the PERV virus from a pig cancer cell line, which she says is a world record for researchers using CRISPR. The next step, she says, is to tweak the porcine genome further to prove the organs can be compatible with the human immune system.

Resurrecting aScientific Vision

For decades, xenotransplantation research seemed impossibly dangerous and financially risky both for small biomedical companies and large pharmaceutical companies. In the early 2000s, Novartis stopped funding xenotransplantation research. The U.S. Food Administration, fearing a public health disaster, began placing regulations on research facilities, whichmade studies even more challenging. The projects were costly andtoo complicated, and animal rights activists frequentlytargeted the scientists. But CRISPR is reviving the area of research once again, says Yang.

Transgenic PERV-free pigs could provide a source for solid organs as well as islet cells, which are tiny cells scattered throughout the pancreas that secrete insulin. Some successful pilot studies looked at porcine islet cell transfusions as a potential treatment for diabetes.

Dixon Kaufman, president-elect of the American Society of Transplant Surgeons and a transplant surgeon at the University of Wisconsin School of Medicine and Public Health, says its only a matter of timeprobably a few yearsbefore xenotransplant studies are open to patients. I think it is a realistic, almost palpable opportunity, he says. Anything that will improve safety, such as deleting this risk of the PERV infection, makes this more viable.

Kaufman thinks kidneys and pancreases will be the first solid animal organs transplanted into humans. Because these are non-vital organs, failure wouldnt necessarily lead to death. Patients who need a kidney could still receive dialysis, and those who need a pancreas could still access insulin.

These advances are a boon for transplant surgeons like Kaufman, who regularly have to tell patientsthey will probably die before a donated organ becomes available. He doesnt think a pig organ would be a hard sell to most of these patients, who are otherwise facing certain death.

The field is inherently sort of risky to begin with, and I think a lot of patients have already processed that, he says. I tell patientsin the grand designwe were not meant to swap body parts between ourselves.

More:
How Gene Editing And Pig Organs Can End The Human Transplant Shortage - Newsweek

The Department of Human Genetics is the youngest basic science department in the Geffen School of Medicine at UCLA. When the Department was launched just prior to the sequencing of the human genome, it was clear that the practice of genetics research would be forever changed by the infusion of massive amounts of new data. Organizing and making sense of this genomic data is one of the greatest scientific challenges ever faced by mankind. The knowledge generated will ultimately transform medicine through patient-specific treatments and prevention strategies.

The Department is dedicated to turning the mountains of raw genetic data into a detailed understanding of the molecular pathogenesis of human disease. The key to such understanding is the realization that genes not only code for specific proteins, but they also control the temporal development and maturation of every living organism through a complex web of interactions.

Housed in the new Gonda Research Center, the Department serves as a focal point for genetics research on the UCLA campus, with state of the art facilities for gene expression, sequencing, genotyping, and bioinformatics. In addition to its research mission, the Department offers many exciting training opportunities for graduate students, postdoctoral fellows, and medical residents. Our faculty and staff welcome inquiries from prospective students. We also hope that a quick look at our web pages will give you a better idea of the Department's research and educational activities.

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UCLA Human Genetics

MONDAY, June 5, 2017 (HealthDay News) -- Genetically tuning a person's own immune cells to target cancer appears to provide long-lasting protection against a blood cancer called multiple myeloma, an early trial from China shows.

The treatment, called CAR T-cell therapy, caused 33 out of 35 patients with recurring multiple myeloma to either enter full remission or experience a significant reduction in their cancer.

The results are "impressive," said Dr. Len Lichtenfeld, deputy chief medical officer for the American Cancer Society.

"These are patients who have had prior treatment and had their disease return, and 100 percent of the patients are reported to have had some form of meaningful response to these cells that were administered," Lichtenfeld said.

The new therapy is custom-made for each patient. Doctors collect the patient's own T-cells -- one of the immune system's main cell types -- and genetically reprogram them to target and attack abnormal multiple myeloma cells.

Lead researcher Dr. Wanhong Zhao likened the process to fitting immune cells with a GPS that steers them to cancer cells -- making them into professional killers that never miss their target.

Zhao is associate director of hematology at the Second Affiliated Hospital of Xi'an Jiaotong University in Xi'an, China.

CAR T-cell therapy is promising because the genetically altered T-cells are expected to roost in a person's body, multiplying and providing long-term protection, Lichtenfeld said.

"The theory is they should attack the tumor and continue to grow to become a long-term monitoring and treatment system," Lichtenfeld said. "It's not a one-shot deal."

The technology represents the next step forward in immunotherapy for cancer, said Dr. Michael Sabel, chief of surgical oncology at the University of Michigan.

"Immunotherapy is now really providing hope to a lot of patients with cancers that were not really responding to our standard chemotherapies," Sabel said.

CAR T-cell therapy previously has been used to treat lymphoma and lymphocytic leukemia, Lichtenfeld said.

Zhao and his colleagues decided to try the therapy to treat multiple myeloma. They re-engineered the patients' T-cells and then reintroduced them to the body in three infusions performed within one week.

Multiple myeloma is a cancer that occurs in plasma cells, which are mainly found in bone marrow and produce antibodies to fight infections. About 30,300 people will likely be diagnosed with multiple myeloma this year in the United States, researchers said in background notes.

"Multiple myeloma is a disease that historically was fatal in the course of a couple of years," Lichtenfeld said. During the past two decades, new breakthroughs have extended survival out 10 to 15 years in some patients, he noted.

To date, 19 of the first 35 Chinese patients have been followed for more than four months, researchers report.

Fourteen of those 19 patients have reached the highest level of remission, researchers report. There hasn't been a relapse among any of these patients, including five followed for more than a year.

"That's as far as you can go in terms of driving down the amount of tumor that's in the body," Lichtenfeld said.

Out of the remaining five patients, one experienced a partial response and four a very good response, researchers said.

However, about 85 percent of the patients experienced cytokine release syndrome (CRS), a potentially dangerous side effect of CAR T-cell therapy.

Symptoms of cytokine release syndrome can include fever, low blood pressure, difficulty breathing, and impaired organ function, the researchers said. However, most of the patients experienced only transient symptoms, and "now we have drugs to treat it," Lichtenfeld said.

History suggests the therapy will cost a lot if it receives approval, Lichtenfeld said. However, prior to approval, much more research will be needed, he added.

The Chinese research team plans to enroll a total of 100 patients in this clinical trial at four hospitals in China. They also plan a similar clinical trial in the United States by 2018, Zhao said.

The study was funded by Nanjing Legend Biotech Co., the Chinese firm developing the technology.

The findings were presented Monday at the American Society of Clinical Oncology annual meeting, in Chicago. Data and conclusions presented at meetings are usually considered preliminary until published in a peer-reviewed medical journal.

Link:
Gene-Based Therapy May Thwart a Tough Blood Cancer - Montana Standard

MOUNTAIN VIEW, CA--(Marketwired - May 15, 2017) - SENS Research Foundation (SRF) has launched a new research program focused on somatic gene therapy in collaboration with the Buck Institute for Research on Aging. Brian Kennedy, PhD, a leading expert on the biology of aging, will be running the project in his lab at the Buck.

Many potential treatments of age-related diseases require the addition of new genes to the genome of cells in the body, a technology known as somatic gene therapy. The technology has been hampered, up until now, by the inability to control where the gene is inserted. That lack of control resulted in a significant risk of insertion in a location that encourages the cell to become malignant.

SRF has devised a new method for inserting genes into a pre-defined location. In this program, this will be done as a two-step process, in which first CRISPR is used to create a "landing pad" for the gene, and then the gene is inserted using an enzyme that only recognizes the landing pad. SRF has created "maximally modifiable mice" that already have the landing pad, and this project will evaluate how well the insertion step works in different tissues.

"Somatic gene therapy has been a goal of medicine for decades. Being able to add new healthy genes will enable us to address treatments of such age-related diseases as atherosclerosis and macular degeneration. Our collaboration with SRF will substantially move us toward finding effective treatments to genetically based age-related diseases," said Dr. Kennedy.

"Partnering with Brian Kennedy and the Buck enables SRF to continue towards our goal of achieving human clinical trials on rejuvenation biotechnologies in the next five years. Brian's leadership in moving this technology into mammals is a huge step forward," said Dr. Aubrey de Grey, CSO, SENS Research Foundation.

This research has been made possible through the generous support of the Forever Healthy Foundation and its founder Michael Greve, as well as the support of our other donors. The Forever Healthy Foundation is a private nonprofit initiative whose mission is to enable people to vastly extend their healthy lifespans and be part of the first generation to cure aging. In order to accelerate the development of therapies to bring aging under full medical control, the Forever Healthy Foundation directly supports cutting-edge research aimed at the molecular and cellular repair of damage caused by the aging process.

About SENS Research Foundation (SRF)SENS Research Foundation is a 501(c)(3) nonprofit that works to research, develop, and promote comprehensive regenerative medicine solutions for the diseases of aging. SRF is focused on a damage repair paradigm for treating the diseases of aging, which it advances through scientific research, advocacy, and education. SENS Research Foundation supports research projects at universities and institutes around the world with the goal of curing such age-related diseases as macular degeneration, heart disease, cancer, and Alzheimer's disease. Educating the public and training researchers to support a growing regenerative medicine field are also major endeavors of the organization that are being accomplished though advocacy campaigns and educational programs. For more information, visit http://www.sens.org.

About Buck Institute for Research on AgingBuck Institute is the U.S.'s first independent research organization devoted to Geroscience -- focused on the connection between normal aging and chronic disease. Based in Novato, California, the Buck is dedicated to extending "healthspan," the healthy years of human life, and does so by utilizing a unique interdisciplinary approach involving laboratories studying the mechanisms of aging and others focused on specific diseases. Buck scientists strive to discover new ways of detecting, preventing and treating age-related diseases such as Alzheimer's and Parkinson's, cancer, cardiovascular disease, macular degeneration, osteoporosis, diabetes and stroke. In their collaborative research, they are supported by the most recent developments in genomics, proteomics, bioinformatics and stem cell technologies. For more information: http://www.thebuck.org.

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SENS Research Foundation Announces New Research Program on Somatic Gene Therapy With Buck Institute for ... - Marketwired (press release)

Scientists from University College London and Imperial College London in the United Kingdom have identified new genetic locations that might make some people more prone to developing type 2 diabetes.

Type 2 diabetes affects hundreds of millions of people worldwide, and the numbers have skyrocketed in recent years. According to the World Health Organization (WHO), the number of people with diabetes has almost quadrupled in the past few decades, from 108 million in 1980 to 422 million in 2014.

In the United States, 29 million people currently have diabetes, and 86 million are thought to have prediabetes.

Until now, researchers were aware of 76 chromosomal locations, or "loci," that underlie this metabolic disease. However, new research analyzed the human genome further and found an additional 111.

The new study - published in the American Journal of Human Genetics - was co-led by Dr. Nikolas Maniatis of University College London's (UCL) Genetics, Evolution, and Environment department, together with Dr. Toby Andrew of Imperial College London's Department of Genomics of Common Disease.

Using a UCL-developed method of genetic mapping, Maniatis and team examined large samples of European and African American people, summarizing 5,800 cases of type 2 diabetes and almost 9,700 healthy controls.

They found that the new loci - together with the ones previously identified - control the expression of more than 266 genes surrounding the genetic location of the disease.

Most of the newly discovered loci were found outside of the coding regions of these genes, but within so-called hotspots that change the expression of these genes in body fat.

Of the newly identified 111 loci, 93 (or 84 percent) were found in both European and African American population samples.

After identifying genetic loci, the next step was to use deep sequence analysis to try to determine the genetic mutations responsible for the disease.

Maniatis and colleagues used deep sequencing to further examine three of the cross-population loci with the aim of identifying the genetic mutations. They then investigated a different sample of 94 Europeans with type 2 diabetes, as well as 94 healthy controls.

The researches found that the three loci coincided with chromosomal regions that regulate gene expression, contain epigenetic markers, and present genetic mutations that have been suggested to cause type 2 diabetes.

Dr. Winston Lau, of UCL's Genetics, Evolution, and Environment department, explains the significance of these findings:

"Our results mean that we can now target the remaining loci on the genetic maps with deep sequencing to try and find the causal mutations within them. We are also very excited that most of the identified disease loci appear to confer risk of disease in diverse populations such as African Americans, implying our findings are likely to be universally applicable and not just confined to Europeans."

Dr. Maniatis also highlights the contribution their study brings to the research community:

"No disease with a genetic predisposition has been more intensely investigated than type 2 diabetes. We have proven the benefits of gene mapping to identify hundreds of locations where causal mutations might be across many populations, including African Americans. This provides a larger number of characterized loci for scientists to study and will allow us to build a more detailed picture of the genetic architecture of type 2 diabetes," says the lead author.

Dr. Andrew also adds, "Before we can conduct the functional studies required in order to better understand the molecular basis of this disease, we first need to identify as many plausible candidate loci as possible. Genetic maps are key to this task, by integrating the cross-platform genomic data in a biologically meaningful way."

Learn how gene discovery could yield new treatments for type 2 diabetes.

Excerpt from:
Scientists find new genetic locations for type 2 diabetes - Medical News Today

From left, Dr. Teresa Sim, Dr. Magdalena Walkiewicz and Dr. Jason Heaney discuss their recent paper in the American Journal of Human Genetics.

An international team of researchers from institutions around the world, including Baylor College of Medicine, has discovered that mutations of the OTUD6B gene result in a spectrum of physical and intellectual deficits. This is the first time that this gene, whose functions are beginning to be explored, has been linked to a human disease. The study appears in the American Journal of Human Genetics.

Our interest in this gene began when we carried out whole exome sequencing the analysis of all the protein-coding genes of one of our patients who had not received a genetic diagnosis for his condition that includes a number of intellectual and physical disabilities, said co-first author Dr. Teresa Sim, a postdoctoral associate of molecular and human genetics and a fellow in Clinical Molecular Genetics and Genomics. We identified OTUD6B, a gene that until now had not been linked to a health condition.

We identified a presumed loss-of-function mutation in the OTUD6B gene in our first patient, said co-senior author Dr. Magdalena Walkiewicz, assistant professor of molecular and human genetics at Baylor and assistant laboratory director at Baylor Genetics. We discovered that this gene seemed to be highly involved in human development; when the gene cannot fulfill its function, the individual presents with severe intellectual disability, a brain that does not develop as expected and poor muscular tone that limits the ability to walk, as well as cardiovascular problems.

Making a convincing case for OTUD6B

However, one case does not represent sufficient evidence to support the involvement of OTUD6B in the medical condition.

To make a convincing case that this gene is essential for human development we needed to find more individuals carrying mutations in OTUD6B, Walkiewicz said.

Mutations in OTUD6B are rare so the researchers had to look into the exomes all the protein-coding genes of a large number of individuals to find others carrying mutations in this gene. Walkiewicz and her colleagues first looked into their clinical exome database at Baylor Genetics labs, specifically into the data of nearly 9,000 unrelated, mostly pediatric-age individuals, many of which carrying neurologic conditions, and found an additional individual carrying genetic changes in the same gene. The clinical characteristics of this individual were strikingly similar to those of the first patient, which led the team to expand their search for more patients.

When we study very rare disorders we rely on collaborations with scientists around the world to find other families affected by mutations in one gene, said Walkiewicz.

One of the strategies that helps researchers find more cases is running the gene of interest through GeneMatcher, a web-tool developed as part of the Baylor-Hopkins Center for Mendelian Genomics for rare disease researchers. Similar to online dating websites that match couples, GeneMatcher allows researchers to find others that are interested in the same genes they are working on.

Without this type of collaborations it would be very difficult to make a convincing case. Between GeneMatcher and our database we found a total of 12 individuals carrying mutations in OTUD6B and presenting with similar clinical characteristics, Walkiewicz said.

An animal model corroborates the human findings

Animal models are one way to determine whether a change in this gene is actually causing the condition, said co-senior author Dr. Jason Heaney, assistant professor of molecular and human genetics and director of the Mouse Embryonic Stem Cell Core at Baylor. Having a similar change in an animal model gene that results in similar characteristics in a mouse can show us whether the gene is causing the condition.

Baylor is part of the International Mouse Phenotyping Consortium. Its goal is to generate a knockout model for every gene in the mouse genome, about 20,000 protein-coding genes, and determine what each gene is involved with.

In this case we learned in the animal model lacking the OTUD6B gene that the gene is highly expressed in the brain and we knew that the patients had reduced intellectual capacities. The animals had cardiovascular defects very similar to those in the patient population. The animal models allowed us to see that having this mutation of this gene causes the clinical characteristics observed in the patients. It highlights how useful animal models can be for understanding human disease, Heaney said.

Through multiple lines of evidence the researchers have established that mutations in OTUD6B can cause a range of neurological and physical conditions and highlight the role of this gene in human development.

In addition, our collaborators in Germany performed functional analysis for this gene on blood cells from patients, Walkiewicz said. Their findings suggest that the OTUD6B protein contributes to the function of proteasomes, large molecular complexes that are at the center of the cellular process that degrades proteins that are damaged or are not needed by the cell. This discovery strengthens the notion that disturbances of the proteasome can cause human disease.

There is interest in better understanding the mechanisms of the disorder at the cellular and molecular level. By understanding the processes that lead to the disease, we can then hope to develop therapies for those patients, said Walkiewicz. One of the highlights of this project is the tremendous collaboration with a number of different centers and labs and putting this tremendous effort together resulted in a publication that is very strong.

Another important contribution of this project is that we provided some answers for the families, and brought them together which offers the opportunity of mutual support, said Sim.

For a complete list of the authors and their affiliations and financial support for this project click here.

Read more from the original source:
OTUD6B gene mutations cause intellectual, physical disability - Baylor College of Medicine News (press release)

A potential cure for Type 1 diabetes looms on the horizon in San Antonio, and the novel approach would also allow Type 2 diabetics to stop insulin shots.

The discovery, made at The University of Texas Health Science Center, now called UT Health San Antonio, increases the types of pancreatic cells that secrete insulin.

UT Health San Antonio researchers have a goal to reach human clinical trials in three years, but to do so they must first test the strategy in large-animal studies, which will cost an estimated $5 million.

Those studies will precede application to the U.S. Food and Drug Administration for Investigational New Drug (IND) approval, Bruno Doiron, Ph.D., a co-inventor, said.

U.S. patent

The scientists received a U.S. patent in January, and UT Health San Antonio is spinning out a company to begin commercialization.

The strategy has cured diabetes in mice.

It worked perfectly, Dr. Doiron, assistant professor of medicine at UT Health, said. We cured mice for one year without any side effects. Thats never been seen. But its a mouse model, so caution is needed. We want to bring this to large animals that are closer to humans in physiology of the endocrine system.

Ralph DeFronzo, M.D., professor of medicine and chief of the Division of Diabetes at UT Health, is co-inventor on the patent. He described the therapy:

The pancreas has many other cell types besides beta cells, and our approach is to alter these cells so that they start to secrete insulin, but only in response to glucose [sugar], he said. This is basically just like beta cells.

Insulin, which lowers blood sugar, is only made by beta cells. In Type 1 diabetes, beta cells are destroyed by the immune system and the person has no insulin. In Type 2 diabetes, beta cells fail and insulin decreases. At the same time in Type 2, the body doesnt use insulin efficiently.

Incorporating genes into the pancreas

The therapy is accomplished by a technique called gene transfer. A virus is used as a vector, or carrier, to introduce selected genes into the pancreas. These genes become incorporated and cause digestive enzymes and other cell types to make insulin.

Gene transfer using a viral vector has been approved nearly 50 times by the U.S. Food & Drug Administration to treat various diseases, Dr. DeFronzo said. It is proven in treating rare childhood diseases, and Good Manufacturing Processes ensure safety.

Unlike beta cells, which the body rejects in Type 1 diabetes, the other cell populations of the pancreas co-exist with the bodys immune defenses.

If a Type 1 diabetic has been living with these cells for 30, 40 or 50 years, and all were getting them to do is secrete insulin, we expect there to be no adverse immune response, Dr. DeFronzo said.

Second-by-second sugar control

The therapy precisely regulates blood sugar in mice. This could be a major advance over traditional insulin therapy and some diabetes medications that drop blood sugar too low if not closely monitored.

A major problem we have in the field of Type 1 diabetes is hypoglycemia (low blood sugar), Dr. Doiron said. The gene transfer we propose is remarkable because the altered cells match the characteristics of beta cells. Insulin is only released in response to glucose.

People dont have symptoms of diabetes until they have lost at least 80 percent of their beta cells, Dr. Doiron said.

We dont need to replicate all of the insulin-making function of beta cells, he said. Only 20 percent restoration of this capacity is sufficient for a cure of Type 1.

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Gene transfer cures diabetes in mice without side effect - Next Big Future

Welcome to theNational Academies of Sciences, Engineering, and Medicine study that examined a range of questions about gene drive research.The study wasconducted by acommittee of expertsand released June 8, 2016.

Gene drives are systems of biased inheritance that enhance the ability of a genetic element to pass from an organism to its offspring through sexual reproduction. A wide variety of gene drives occur in nature. Researchers have been studying these natural mechanisms throughout the 20th century but, until the advent of CRISPR/Cas9[1] for gene editing, have not been able to develop a gene drive.

Since early 2015, laboratory scientists have published four proofs-of-concept showing that a CRISPR/Cas9-based gene drive could spread a targeted gene through nearly 100% of a population of yeast, fruit flies, or mosquitoes. Biologists have proposed using gene drives to address problems where solutions are limited or entirely lacking, such as the eradication of insect-borne infectious diseases and the conservation of threatened and endangered species. This study provided an independent, objective examination of what has been learned since the development of gene drivesbased on current evidence.

The resulting report, Gene Drives on the Horizon outlines the state of knowledge relative to the science, ethics, public engagement, and risk assessment as they pertain to gene drive research and the governance of the research process. This report offers principles for responsible practices of gene drive research and related applications for use by investigators, their institutions, the research funders, and regulators.

Follow on Twitter:#GeneDriveStudy

Send email to:ksawyer@nas.edu

[1] CRISPR (Clustered regularly-interspaced short palindromic repeats) are segments of bacterial DNA that, when paired with a specific guide protein, such as Cas9 (CRISPR-associated protein 9), can be used to make targeted cuts in an organisms genome

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Gene Drive Research in Non-Human Organisms ...

BOSTON (January 27, 2010) Researchers at Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences at Tufts have developed a new tool for gene therapy that significantly increases gene delivery to cells in the retina compared to other carriers and DNA alone, according to a study published in the January issue of The Journal of Gene Medicine. The tool, a peptide called PEG-POD, provides a vehicle for therapeutic genes and may help researchers develop therapies for degenerative eye disorders such as retinitis pigmentosa and age-related macular degeneration.

For the first time, we have demonstrated an efficient way to transfer DNA into cells without using a virus, currently the most common means of DNA delivery. Many non-viral vectors for gene therapy have been developed but few, if any, work in post-mitotic tissues such as the retina and brain. Identifying effective carriers like PEG-POD brings us closer to gene therapy to protect the retinal cells from degeneration, said senior author Rajendra Kumar-Singh, PhD, associate professor of ophthalmology and adjunct associate professor of neuroscience at Tufts University School of Medicine (TUSM) and member of the genetics; neuroscience; and cell, molecular, and developmental biology program faculties at the Sackler School of Graduate Biomedical Sciences at Tufts.

Safe and effective delivery of therapeutic genes has been a major obstacle in gene therapy research. Deactivated viruses have frequently been used, but concerns about the safety of this method have left scientists seeking new ways to get therapeutic genes into cells.

We think the level of gene expression seen with PEG-POD may be enough to protect the retina from degeneration, slowing the progression of eye disorders and we have preliminary evidence that this is indeed the case, said co-author Siobhan Cashman, PhD, research assistant professor in the department of ophthalmology at TUSM and member of Kumar-Singhs lab.

What makes PEG-POD especially promising is that it will likely have applications beyond the retina. Because PEG-POD protects DNA from damage in the bloodstream, it may pave the way for gene therapy treatments that can be administered through an IV and directed to many other parts of the body, said Kumar-Singh.

Kumar-Singh and colleagues used an in vivo model to compare the effectiveness of PEG-POD with two other carriers (PEG-TAT and PEG-CK30) and a control (injections of DNA alone).

Gene expression in specimens injected with PEG-POD was 215 times greater than the control. While all three carriers delivered DNA to the retinal cells, PEG-POD was by far the most effective, said first author Sarah Parker Read, an MD/PhD candidate at TUSM and Sackler and member of Kumar-Singhs lab.

Age-related macular degeneration, which results in a loss of sharp, central vision, is the number one cause of vision loss in Americans age 60 and older. Retinitis pigmentosa, an inherited condition resulting in retinal damage, affects approximately 1 in 4,000 individuals in the United States.

This study was supported by grants from the National Eye Institute of the National Institutes of Health, the Foundation for Fighting Blindness, The Ellison Foundation, The Virginia B. Smith Trust, the Lions Eye Foundation, and Research to Prevent Blindness. Sarah Parker Read is part of the Sackler/TUSM Medical Scientist Training Program, which is funded by the National Institute of General Medical Sciences, part of the National Institutes of Health.

Read SP, Cashman SM, Kumar-Singh R. The Journal of Gene Medicine. 2010 (January). 12(1): 86-96. A poly(ethylene) glycolylated peptide for ocular delivery compacts DNA into nanoparticles for gene delivery to post-mitotic tissues in vivo. Doi: 10.1002/jgm.1415

About Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences

Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences at Tufts University are international leaders in innovative medical education and advanced research. The School of Medicine and the Sackler School are renowned for excellence in education in general medicine, biomedical sciences, special combined degree programs in business, health management, public health, bioengineering and international relations, as well as basic and clinical research at the cellular and molecular level. Ranked among the top in the nation, the School of Medicine is affiliated with six major teaching hospitals and more than 30 health care facilities. Tufts University School of Medicine and the Sackler School undertake research that is consistently rated among the highest in the nation for its impact on the advancement of medical science.

If you are a member of the media interested in learning more about this topic, or speaking with a faculty member at the Tufts University School of Medicine, the Sackler School of Graduate Biomedical Sciences, or another Tufts health sciences researcher, please contact Siobhan Gallagher at 617-636-6586 or, for this study, Lindsay Peterson at 617-636-2789.

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Researchers develop new tool for gene delivery - ScienceBlog.com (blog)

THURSDAY, March 23, 2017 (HealthDay News) -- Researchers say they have found the genetic cause of a rare disorder that causes children to be born with deafness, blindness, albinism and fragile bones.

The syndrome is called COMMAD. It occurs when children inherit two mutations -- one from each parent -- of a gene called MITF. Each parent is also deaf due to another rare genetic disorder called Waardenburg syndrome 2A.

Further research is needed to learn more about the role of MITF during early development and how mutations in this gene result in the development of Waardenburg 2A and COMMAD, said researchers from the U.S. National Eye Institute (NEI).

COMMAD stands for the names of a number of conditions that affect people with this disorder. It includes missing tissue around the eye; abnormally dense bones prone to fracture; small or abnormally formed eyes; an abnormally large head; albinism (lack of melanin in the skin, eyes and hair), and deafness.

Identifying the genetic cause of COMMAD is important because deaf people commonly choose to marry other deaf persons. People who are deaf may not know that their deafness is associated with Waardenburg 2A, the researchers explained.

Deaf couples may want to consider genetic counseling prior to conceiving a child. If both potential parents have Waardenburg 2A, they risk passing mutated versions of MITF to their children, who would then have COMMAD, study lead author Dr. Brian Brooks said in a NEI news release.

Brooks is chief of the NEI's Pediatric, Developmental, and Genetic Ophthalmology section.

The study describes two unrelated cases of children born with COMMAD who inherited the two mutations of MITF from their parents.

Most people who are born deaf don't have Waardenburg 2A. Along with hearing loss, people with the syndrome have premature graying of the hair, blue eyes, fair skin and sometimes vision problems, the researchers said.

The study was published recently in the American Journal of Human Genetics.

Link:
Scientists Spot Gene for Rare Disorder Causing Deafness, Blindness - Montana Standard

I love working with people, says Allison Werner-Lin of the School of Social Policy & Practice (SP2). Werner-Lins office overlooking Locust Walk is homey and lamp-lit, with student gifts sharing space with scholarly tomes. This is just one of her workspaces, however. Recently returned from sabbatical, Werner-Lin has been working with the National Cancer Institute (NCI), as well as out of her home in upstate New York, which doubles as a private practice for families seeking bereavement therapy. The divide between academia and clinical practice suits her. I feel like I have one foot in each world and in a very positive way, Werner-Lin says.

Werner-Lin has extensive clinical and research experience and uses both to inform her work, which centers on heritable cancers. She began her academic work studying young adults with mutations in genes associated with breast and ovarian cancer, BRCA1 and BRCA2. Recently, her work with the NCI has branched out to the study of Li-Fraumeni syndrome (LFS). Patients with LFS have a mutation in a tumor-suppression gene, resulting in a high incidence of cancer starting in childhood, and 50% of LFS patients develop cancer by age 40. Both patient populations make life-altering decisions based upon their family histories and medical diagnoses.

Dr. Werner-Lins groundbreaking research merges science with social work at the intersection of qualitative health research, the structure and evolution of genes, hereditary cancer, and how it impacts individuals and families at various stages of life, says SP2 Dean Sara Sally Bachman. Each day, Allison is pushing the frontiers of genomic study and oncological social work while also mentoring other social change agents who will undoubtedly make a difference locally, nationally, and internationally.

For more than a decade, Werner-Lin has worked in the Clinical Genetics Branch of the Division of Cancer Epidemiology and Genetics of the NCI organizing the human side of research. Patients come annually to the NCI to receive full-body MRI cancer screenings and participate in data collection that covers everything from cancer history to family communication to risk management. Werner-Lin mentors an interdisciplinary team of predoctoral and postdoctoral fellows to explore how these families understand and cope with genetic information. Her work is used to train providers in delivering holistic medical and psychological care.

We talk with families about their experiences communicating cancer-risk information with loved ones, making reproductive decisions, and managing the endless cycle of screening, Werner-Lin says. She has seen patterns in how families share cancer-risk information and seek support, noting that information travels based on relationship patterns and emotional closeness, not necessarily degree of risk.

People with LFS have limited options for cancer prevention, and expectations for a cancer diagnosis and early death are common. Were seeing a lot of physical loss, where amputations and other changes in physical function are common consequences of treatment.

Many of the people Werner-Lin speaks with are looking at different pathways to parenthood or are choosing not to have children at all, she says. Grief becomes a chronic part of their lives, and those kinds of sustained of losses can connect individuals in and across families.

Former SP2 graduate student Catherine Wilsnack is a Cancer Research Training Award Fellow at the NCI, doing qualitative research as part of Werner-Lins team. Wilsnack first met Werner-Lin while in her second year at SP2 and calls the encounter transformative. Werner-Lin is a phenomenal mentor in every way, says Wilsnack, who earned her masters in social work (MSW) in 2019. She always goes above and beyond for her students. I would not be where I am today if it were not for her and her guidance, so I just feel extremely lucky.

Now in midcareer, Werner-Lin is taking the time to mentor younger generations. There are so many opportunities to focus on other peoples career development without such a bounded focus on my own professional needs, she says, crediting her own mentors with the ability to achieve professional success.

At Penn, Werner-Lin is involved in the Cancer Moonshot initiative led by Katherine Nathanson and Steve Joffe, an effort designed to accelerate cancer research aimed at prevention, detection, and treatment. Werner-Lins aspect of the project, based at the Abramson Cancer Center at Penn Medicine, involves issues surrounding genetic testing in people aged 18 through 40. Susan Domchek, executive director of the Basser Center for BRCA, says, Allisons work in terms of the psychosocial implications of having a BRCA mutationhow an individual can come to terms with that and how that information gets disseminated between familieshas been extremely helpful. She has a deep expertise on helping families navigate these situations.

Approximately 1 in 400 people carry mutated breast cancer genes, though mutations are more common in certain groups of people. The gene mutations are passed in an autosomal dominant pattern, meaning each parent with a mutation has a 50% chance of passing it on. Children of a BRCA-positive parent can pursue genetic testing to learn if they carry the mutation, adding pressure to family planning.

Werner-Lin was one of these children. Her mother has a BRCA1 mutation. She recovered from colon cancer when Werner-Lin was in college and is currently in remission from a rare ovarian cancer. When I was 23 and was thinking about having kids, I couldnt figure out how to do it, Werner-Lin says. I started talking to people, talking to other women, and that became my dissertation.

This curiosity and compassion led Werner-Lin to operate a private therapy practice out of her home, where she exclusively sees children and young adults with a deceased parent. People often dont see how therapy is connected to the genetics part of my work, but for me they are inseparable, Werner-Lin says. In my cancer work, parents often die young, leaving small children. Frequently, the children of cancer patients conflate their parents lives with their own, not seeing options, degrees of freedom, or technological innovation.

Working together with an MSW student, Werner-Lin does whole family-therapy, from diagnosis to end-of-life, through the grieving process. She helps to facilitate goodbyes, talks about legacy building, and makes the concept of death more concrete for young people.

The language adults use to talk about death is often confusing and shrouded in existential concepts, Werner-Lin says, citing references to angels or going to a better place. Young kids dont necessarily understand time or geography, she says. If were in New York, and Mommy went to the other side, is that a better place?

Instead, she says, we talk about the brain being a light switch, and once you turn it off you cant turn it on again. We talk about how the heart stops beating and the eyes stop seeing. These practical realities are important, Werner-Lin says. Kids need to understand the way the world is predictable, especially when people they love and need can fall off the earth at any moment.

Now back on campus, Werner-Lin is focusing on teaching and engaging with her graduate students. Acting in service to her patients, her students, and her colleagues is a core part of Werner-Lins brand of academia. If you tell her that you want to do something, Wilsnack says, she will go out of her way to help.

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Working on 'the human side' of heritable cancers - Penn: Office of University Communications

Media Advisory

Tuesday, March 31, 2020

Findings provide insight that may inform search for treatments.

Researchers at the National Institutes of Health have discovered a second gene that causes melorheostosis, a rare group of conditions involving an often painful and disfiguring overgrowth of bone tissue. The gene, SMAD3, is part of a pathway that regulates cell development and growth. The researchers are now working to develop an animal model with a mutant version of SMAD3 to test potential treatments for the condition. The study appears in the Journal of Experimental Medicine.

Melorheostosis affects about 1 in 1 million people. Its causes have long been unknown. DNA tests of blood and skin could not identify a mutation. The key to finding the gene was to biopsy the affected bone directly and compare it to unaffected bone. Earlier, the researchers used this method to discover the gene for dripping candle wax bone disease, a form of melorheostosis in which excess bone growth appears to drip from the bone surface like hot wax. In that study, mutations in the gene MAP2K1 accounted for eight cases of the disease among 15 patients.

In the current study, researchers scanned the exome the part of the genome that codes for proteins and found mutations in the affected bone. These mutations occurred during the patients lifetime rather than being inherited from parents and are not present in all the cells of the body.

The researchers found SMAD3 mutations in four of the patients who did not have mutations in MAP2K1. SMAD3 is involved in a pathway crucial for skeletal development both before and after birth. The SMAD3 mutations increase the maturation of bone-forming cells and are involved in a cellular pathway distinct from the MAPK2K1 pathway.

The study was conducted by researchers at NIHs Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Arthritis and Musculoskeletal and Skin Diseases and the NIH Clinical Center, as well as the Ludwig-Boltzmann Institute of Osteology at the Hanusch Hospital in Vienna, Austria.

Senior author Joan Marini, M.D., chief of the NICHD Section on Heritable Disorders of Bone and Extracellular Matrix, is available for comment.

Kang, H. et al. Somatic SMAD3 activating mutations cause melorheostosis by upregulating the TGF-/SMAD pathway. Journal of Experimental Medicine. DOI:10.1084/jem.20191499

About the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): NICHD leads research and training to understand human development, improve reproductive health, enhance the lives of children and adolescents, and optimize abilities for all. For more information, visit https://www.nichd.nih.gov.

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIHTurning Discovery Into Health

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NIH researchers discover gene for rare disease of excess bone tissue growth - National Institutes of Health

Reuben Jacob and Fiona Kellas, Maucher Jenkins share their expertise on IP strategies and considerations for gene therapy inventions.

Gene therapy enables the treatment of a disorder or disease through the insertion of a gene into a patients cells instead of using drugs or surgery.This technique involves the introduction of genetic material into cells to compensate for abnormal genes in the patient or to make protein that will be beneficial to the patient.As an example, if a mutated gene causes a protein that is necessary for the correct functioning of cells to be faulty or missing, gene therapy may be able to introduce a normal copy of the gene to restore the function of the protein.Gene therapy is understood to be useful in the treatment of a range of conditions such as cancer, cystic fibrosis, muscular dystrophy and Alzheimers disease.

UK role in gene therapy techR&D

Gene therapy is considered to be very important to the future of medicine and as such, many companies are focussing their research and development into gene therapy technologies.The UK is a growing industry for research into these areas and it is anticipated that by 2035 the UK industry around cell and gene therapy technologies will be worth in the region of 10 billion.Gene therapy research is still at an early stage.Due to this length of time and the associated costs involved in developing an effective gene therapy and taking it through to approval, it will be important for companies working in this area to put into place an effective IP strategy that will provide protection for their inventions and assist them in maintaining their market position.In addition, the competitive nature of the gene therapy industry means that will be important for a company to obtain patent protection for inventions being developed, as well as reviewing the patent landscape to check that the company is free to operate in their chosen area.

What makes something patentable?

In order for an invention to be patentable, it must be new, inventive and capable of industrial application.In addition to the requirement that an invention meets the above requirements of patentability, it is also important that the invention does not contain subject matter that is excluded from patentability.One of the challenges associated with obtaining patent protection for gene therapy inventions is that the European and US patent systems include a number of exceptions to patentability that are relevant to biological material and natural products.In Europe, it is not possible to obtain patent protection for a method of treatment or surgery of the human body.Thus, the removal of cells from a patient would not be considered to be patentable in Europe.In addition, inventions relating to stem cells that are derived from the destruction of human embryos are not patentable in Europe.In the US, recent case law (Molecular Pathology v Myriad Genetics, Inc, 2013) has meant that inventions relating to natural phenomena and natural products must show characteristics that are different to their natural counterpart(s).

However, despite the above challenges, there are a number of aspects of the gene therapy technology that may be eligible for patent protection.Typically, the gene therapy procedure can involve performing the required modification procedure on cells that have been removed from a patient before reintroducing the cells into the subject to produce their modified effect.The process of modifying the cells may be patentable if it fulfils the above requirements of patentability.In addition, it may be possible to obtain protection for the methods that are used to culture, manipulate or modify the cells that are used for gene therapy.

At Maucher Jenkins, we have a team of attorneys who can provide IP advice and assistance in the area of patenting inventions involving gene therapy, molecular biology and biochemistry.

by Fiona Kellas, Reuben Jacob

16 March 2020

14:20

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Thinking out loud: IP strategies for gene therapy inventions - Med-Tech Innovation

For Immediate Release: February 21, 2020

The U.S. Food and Drug Administration today authorized marketing of the first test to detect a genetic condition known as Fragile X Syndrome (FXS), the most common known cause of inherited developmental delay and intellectual disability. The test is intended as an aid in diagnosing FXS and is to be used along with the evaluation of a patients family history and clinical signs and symptoms of FXS. Additionally, this test is intended for use in adults who may be carriers of genetic alterations in the gene associated with FXS, called the FMR1 gene.

This novel diagnostic provides doctors and their patients the first FDA authorized genetic test to aid in diagnosing Fragile X Syndrome, as well as helping parents know their risk of having a child with Fragile X Syndrome, said Wendy Rubinstein, M.D., Ph.D., director of personalized medicine in the Office of In Vitro Diagnostics and Radiological Health at the FDAs Center for Devices and Radiological Health. Early diagnosis is key to helping children affected with Fragile X Syndrome through early intervention.

According to the Centers for Disease Control and Prevention, approximately 1 in 4,000 males and 1 in 8,000 females in the U.S. have FXS, which is a genetic disorder caused by changes in the FMR1 gene located on the X chromosome. A segment of the DNA in the gene, known as a CGG trinucleotide repeat, is repeated in excess on the X chromosome in individuals with this disorder. While some repetition of the CGG repeat is normal, a high number of repeats may indicate potential health risks. The AmplideX Fragile X Dx and Carrier Screen Kit uses blood specimens from patients to measure the number of repeats of the CGG segment in the FMR1 gene. The test can determine whether a patient has a number of CGG repeats that is considered either normal, intermediate, premutation or full mutation.

Individuals with a full mutation typically have FXS, which is associated with developmental delays, learning disabilities, social and behavioral issues, intellectual disabilities and autism spectrum disorder. Women with a premutation have an increased risk of having a child with FXS as compared to women without a premutation. The number of women who have the Fragile X premutation is believed to be approximately 1 in 150 women. Men with a premutation will pass the premutation to their daughters only. Individuals with normal or intermediate levels of repeated CGG segments are currently thought to be asymptomatic for FXS or other fragile X-associated disorders.

In addition to aiding in the diagnosis of FXS and for carrier testing, this test can be used as an aid in the diagnosis of fragile X-associated disorders, including fragile X-associated tremor/ataxia syndrome, which is a movement and cognitive disorder that typically occurs in adults over age 50, and fragile X-associated primary ovarian insufficiency, a condition that is characterized by reduced function of the ovaries. The AmplideX Fragile X Dx and Carrier Screen Kit is not intended for use in fetal diagnostic testing, the screening of eggs obtained for in-vitro fertilization prior to implantation, or standalone diagnoses of FXS.

The FDA reviewed data for this test through the de novo classification process, a regulatory pathway for low- to moderate-risk devices of a new type. During this process, the FDA evaluated data from specimens collected at three clinical sites to assess the accuracy of the test. The data demonstrated that the diagnostic accuracy of the test is greater than 95%.

Along with this authorization, the FDA is establishing criteria, called special controls, that test developers must meet for tests of this type, including requirements relating to labeling and performance testing. These special controls, when met along with general controls, provide a reasonable assurance of safety and effectiveness for tests of this type. This action also creates a new regulatory classification, which means that subsequent devices of the same type with the same intended use may go through the FDAs 510(k) pathway, whereby devices can obtain clearance by demonstrating substantial equivalence to a predicate device.

The FDA granted marketing authorization of the AmplideX Fragile X Dx and Carrier Screen Kit to Asuragen Inc.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nations food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

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FDA Authorizes Marketing of the First Genetic Test to Aid in the Diagnosis of Fragile X Syndrome - FDA.gov

WASHINGTON, D.C., Feb. 13, 2020 (GLOBE NEWSWIRE) -- via NEWMEDIAWIRE -- The Alliance for Regenerative Medicine (ARM), the international advocacy organization representing the cell and gene therapy and broader regenerative medicine sector, today released the agenda for its second annual Cell & Gene Meeting on the Mediterranean. The event will be held from April 15-17, 2020 in Barcelona, Spain.

The event, modeled after ARMs highly successful Cell & Gene Meeting on the Mesa, is expected to attract more than 500 attendees, including senior executives from leading cell therapy, gene therapy, and tissue engineering companies worldwide, large pharma and biotech representatives, institutional investors, academic research institutions, patient foundations, disease philanthropies, and members of the life science media community.

The agenda includes:

Plenary Session:

Keynote Address:

Panels:

Throughout the two-day event, participants can also attend presentations by more than 50 publicly traded and emerging private companies, highlighting clinical and commercial progress in cell therapy, gene and gene-modified cell therapy, tissue engineering, biomaterials and more. In addition to their presentations, representatives from these organizations will also be available for one-on-one partnering opportunities throughout the conference.

2020 presenting companies include: Adaptimmune, AGTC, Ambys Medicines, AskBio, Aspect Biosystems, Atara Biotherapeutics, Autolus Therapeutics, Avectas, AVROBIO, Axovant Gene Therapies, bluebird bio, Bone Therapeutics, Cabaletta Bio, Caribou Biosciences, Celavie Biosciences, Cellatoz Therapeutics, Cellect Biotherapeutics, CEVEC, Cryoport, Cynata Therapeutics, Flexion Therapeutics, Fraunhofer IZI, Genethon, GenSight Biologics, Healios, Iovance Biotherapeutics, Kiadis Pharma, Kytopen, LogicBio Therapeutics, MeiraGTx, Minerva Biotechnologies, MolMed, Novadip Biosciences, Orchard Therapeutics, Oxford Biomedica, PDC*line Pharma, Polyplus-transfection, Precision BioSciences, Promethera Biosciences, PTC Therapeutics, Recombinetics, REGENXBIO, ReNeuron, Rexgenero, Sangamo, SmartPharm Therapeutics, Standards Coordinating Body for Regenerative Medicine, Theradaptive, ThermoGenesis, Tmunity Therapeutics, Ultragenyx Pharmaceutical, VERIGRAFT, and Vineti.

For full details on the agenda and further information about the event, please visit http://www.meetingonthemed.com.

Registration is complimentary for credentialed members of the media. For members of the media interested in attending, please contact Kaitlyn Donaldson Dupont at kdonaldson@alliancerm.org or Consilium Strategic Communications at ARM@consilium-comms.com.

About the Alliance for Regenerative Medicine

The Alliance for Regenerative Medicine (ARM) is an international multi-stakeholder advocacy organization that promotes legislative, regulatory, and reimbursement initiatives necessary to facilitate access to life-giving advances in regenerative medicine worldwide. Founded in 2009, ARM works to increase public understanding of the field and its potential to transform human healthcare, providing business development and investor outreach services to support the growth of its 350+ member organizations worldwide. ARM represents the interests of therapeutic developers, academic research institutions, major medical centers, investors, and patient groups that comprise the broader regenerative medicine community and is the prominent international advocacy organization in this field.

ARM has 70+ members across 15 countries in Europe. ARM aims to work closely with European stakeholders, leveraging its membership to create a supportive commercial and regulatory environment to create better conditions for the development and commercialization of ATMPs in Europe; develop strong stakeholder support around proposed solutions to improve patient access to ATMPs; promote clear, predictable and efficient regulatory framework across Europe; and promote international convergence of key regulations and guidance. For more information, visit alliancerm.org.

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The Alliance for Regenerative Medicine Releases Agenda for 2020 Cell & Gene Meeting on the Mediterranean - BioSpace

- Salvador Rico, M.D., Ph.D., named Chief Medical Officer

- Martin Moorhead, Ph.D., promoted to Chief Technology Officer

SOUTH SAN FRANCISCO, Calif., Feb. 11, 2020 /PRNewswire/ --Encoded Therapeutics, Inc.(Encoded), a precision gene therapy company,today announced the appointment of Salvador Rico, M.D., Ph.D., as chief medical officer and the promotion of Martin Moorhead, Ph.D., to chief technology officer. Dr. Rico joins Encoded from Audentes Therapeutics, where he led clinical development of the company's pipeline of gene therapies for neuromuscular disorders. In his three years at Encoded, Dr. Moorhead has guided the development of the company's technology platform for creating innovative AAV-based gene therapies. He previously led the development of clonoSEQ, the FDA-approved next-generation sequencing assay for detecting minimal residual disease in lymphoid malignancies, at Adaptive Biotechnologies.

Encoded Therapeutics, Inc. Logo (PRNewsfoto/Encoded Therapeutics, Inc.)

"Sal is an accomplished physician-scientist with deep experience advancing novel therapeutics through clinical development, and Martin is a strong leader who brings a genomics mindset to all aspects of gene therapy development," said Encoded co-founder and chief executive officer Kartik Ramamoorthi, Ph.D."With these appointments, we now have some of the most qualified gene therapy experts in the industry with a proven track record of delivering for patients in need. Their collective experience includes bringing multiple AAV-based gene therapies through clinical development, FDA filings, and approval. I am more confident than ever that our novel gene therapies can make a major impact on patients suffering from debilitating diseases, starting with Dravet Syndrome."

At Encoded, Dr. Rico will lead medical strategy and clinical development of ETX101, which is being developed for patients with SCN1A+ Dravet Syndrome. Dr. Moorhead will lead the technical team that enables Encoded's innovative research platform.

"I am delighted to join an organization that is so committed to transforming patients' lives with the development of next-generation gene therapies," said Dr. Rico. "I look forward to working closely with both the team at Encoded, and with the Dravet Syndrome community, to advance ETX101 through clinical development and ultimately, deliver it to patients in need."

"In building a technology platform that combines the power of genomics and computation with AAV-based gene therapy, Encoded is forging the path for the next generation of precision genetic medicines," said Dr. Moorhead. "I am very proud of what we have accomplished to date and am thrilled at the opportunity to help advance multiple programs for diseases where no treatment options currently exist."

New Leadership Team Appointments

About Encoded

Encoded Therapeutics, Inc., is a biotechnology company developing precision gene therapies for a broad range of severe genetic disorders. Our mission is to realize the potential of genomics-driven precision medicine by overcoming key limitations of viral gene therapy. We focus on delivering life-changing advances that move away from disease management and towards lasting disease modification. We are advancing our lead asset, ETX101, for the treatment of SCN1A-positiveDravet Syndrome. For more information, please visitwww.Encoded.com.

Media Contacts

Sarah SuttonGlover Park Groupssutton@gpg.com 202-337-0808

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SOURCE Encoded Therapeutics, Inc.

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Encoded Therapeutics Expands Gene Therapy Leadership with Key Appointment and Promotion - Yahoo Finance

Updated results from the Alta trial show that a single infusion with the highest dose of SB-525, an investigational gene therapy, yields dose-dependent and durable increases in clotting factor VIII (FVIII). The trial, in adults with severe hemophilia A , found no bleeding episodes up to 24 weeks following the infusion.

That highest dose of SB-525 31013 vector genomes, vg/kilogram, kg led patients to reach normal FVIII activity. Participants no longer needed replacement therapy following a short preventive course post-SB-525-administration.

With these promising results, Pfizer has initiated a lead-in study (NCT03587116) to support SB-525 advancement to a Phase 3 registrational clinical trial. The six-month study will evaluate the current efficacy and safety of preventive replacement therapy in the usual care setting. It is currently recruiting participants worldwide.

The Alta trials most recent findings will be shared at the upcoming 61st Annual Meeting of the American Society of Hematology (ASH), to be held Dec. 7-10 in Orlando, Fla.

Data will be featured in a poster titled Updated Follow-up of the Alta Study, a Phase 1/2, Open Label, Adaptive, Dose-Ranging Study to Assess the Safety and Tolerability of SB-525 Gene Therapy in Adult Patients with Severe Hemophilia A.

SB-525 is a gene therapy candidate to treat hemophilia A thats being developed by Sangamo Therapeutics in collaboration with Pfizer. It consists of a DNA sequence coding for the production of a working FVIII the clotting factor missing in hemophilia A. That FVIII is carried and delivered to liver cells, where clotting factors are produced, using a harmless adeno-associated viral (AAV) vector.

The goal of the therapy is for patients to regain the ability to continuously produce the coagulation factor, and reduce or eliminate the need for FVIII replacement therapy.

The therapys safety and effectiveness for the treatment of adults with severe hemophilia A are currently being evaluated in the open-label Phase 1/2 Alta trial (NCT03061201).

The study is testing a single infusion into the vein (intravenous) of one of four ascending doses of SB-525: 91011 vg/kg; 21012 vg/kg; 11013 vg/kg; and 31013 vg/kg. Two people have been dosed per group, except for the highest dose group, which was expanded to five patients.

Updated trial data now released show the results for the two patients dosed in the third group those given 11013 vg/kg and the five individuals receiving the highest dose of 31013 vg/kg.

In the third group, a single infusion of SB-525 resulted in stable and clinically relevant increases in FVIII activity.

Stronger results were seen with SB-525s highest dose. Of the five patients treated, data were available for four. For these participants, a single infusion with the highest dose of SB-525 led to normal FVIII levels with no bleeding events reported up to 24 weeks post-administration. These individuals no longer needed replacement therapy after the initial prophylactic period of up to about three weeks after SB-525 dosing.

In addition, preliminary tests from the high-dose group indicate similar activity of SB-525-derived FVIII and the clotting factor provided by Xyntha, Pfizers recombinant therapy for hemophilia A.

As to safety, one patient had treatment-related serious adverse events, namely low blood pressure and fever, occurring about six hours after infusion. These effects resolved with treatment within 24 hours, with no loss of FVIII expression.

Some patients also showed elevated blood levels of liver enzymes(ALT, alanine aminotransferase). However, these were reported to be mild and temporary increases, which were treated in a timely manner with corticosteroids.

Dosing in the fourth group is ongoing. At the upcoming meeting, Sangamo will disclose additional analyses of the trial data, including a follow-up of approximately 4 to 11 months after treatment.

The rapid kinetics of Factor VIII expression, durability of response, and the relatively low intra-cohort variability in the context of a complete cessation of bleeding events and elimination of exogenous Factor VIII usage continues to suggest SB-525 is a differentiated hemophilia A gene therapy, Bettina Cockroft, MD, MBA, chief medical officer of Sangamo said in a press release.

We are pleased with the progress of the program toward a registrational Phase 3 study led by Pfizer, who announced it has enrolled its first patient in the 6-month Phase 3 lead-in study. We have recently completed the manufacturing technology transfer to Pfizer and initiated the transfer of the IND [investigational new drug].

Ana is a molecular biologist enthusiastic about innovation and communication. In her role as a science writer she wishes to bring the advances in medical science and technology closer to the public, particularly to those most in need of them. Ana holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she focused her research on molecular biology, epigenetics and infectious diseases.

Total Posts: 121

Margarida graduated with a BS in Health Sciences from the University of Lisbon and a MSc in Biotechnology from Instituto Superior Tcnico (IST-UL). She worked as a molecular biologist research associate at a Cambridge UK-based biotech company that discovers and develops therapeutic, fully human monoclonal antibodies.

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Updated Alta Trial Results Support SB-525 Gene Therapy for Hemophilia A - Hemophilia News Today