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Alzheimer’s attacks more women than men – WNDU-TV

Posted on February 25, 2020 by Danzig

It's a startling number. Every 65 seconds in the U.S., someone develops Alzheimer's disease.

According to new research, there's a biological reason why women are more likely to get the disease.

Harry and Bettie Dunn love to reminisce about their past adventures during their 70 years of marriage.

"I know as you grow older you begin to lose some memory, but I noticed she was losing it more than I was," Harry said.

Harry believes it progressed more rapidly after a bad fall that broke Bettie's hip.

"She really doesn't know people that we've been friends with, sometimes she doesn't know her own children," he said.

"Two-thirds of Alzheimer's patients here in the U.S. are women," said Dr. Sepi Shokouhi, assistant professor of psychiatric and behavioral sciences at Vanderbilt University Medical Center.

Researchers examined 400 brain scans of elderly patients to figure out why the risk for Alzheimer's is higher for women than it is for men. They believe it may have something to do with an abnormal protein in the brain, named tau, which is linked to cognitive impairment.

"These abnormal proteins can spread like infection in the brain," Shokouhi said.

In the study, they found the tau accumulation was more widespread in women's brains than men's, easily moving from one part of the brain to another.

Previous theories on why more women got Alzheimer's disease than men pointed to the fact that women had a longer life expectancy. However, this research also points to a biological reason.

"I can predict that sex will be more strongly integrated in future precision medicine in Alzheimer's disease," Shokouhi said.

The new findings will help to identify therapies that would work best for women.

A study out of University of California at Los Angeles also points to social sex differences when it comes to Alzheimer's disease. They found the rate of memory decline was faster among married women who did not work in the labor force compared to married mothers who did.

Other researchers are studying possible causes like estrogen and one copy of a certain gene.

RESEARCH SUMMARYALZHEIMER'S ATTACKS MORE WOMEN THAN MEN REPORT #2717

BACKGROUND: Nearly 500,000 new cases of Alzheimer's disease will be diagnosed this year in the United States, and every 3 seconds, someone in the world develops dementia. Alzheimer's is the sixth-leading cause of death across all ages in the United States with a 5% increase in number of deaths in the from 2015 to 2016. For those 65 and older, it is the fifth-leading cause of death. Alzheimer's is an irreversible degeneration of the brain that causes disruptions in memory, cognition, personality, and other functions that eventually lead to death from complete brain failure. Caring for a person with Alzheimer's or another dementia is often extremely difficult, and many family and other unpaid caregivers experience high levels of emotional stress and depression as a result. (Source: https://www.brightfocus.org/alzheimers/article/alzheimers-disease-facts-figures)

ALZHEIMER AND GENDER: At the age of 65, women have a 1 in 5 chance of developing Alzheimer's, compared to a 1 in 11 chance for men. And, women in their 60's are twice as likely to develop Alzheimer's than to develop breast cancer. The Alzheimer's Association brought 15 of the world's leading scientists together to look further into why Alzheimer's is more likely in women, stating that "researchers are now questioning whether the risk of Alzheimer's could actually be higher for women at any given age due to biological or genetic variations or differences in life experiences." Genetic studies have offered a surprising account for the difference. Researchers from Stanford University studied over 8,000 people looking for a form of the gene ApoE-4, which increases the risk of Alzheimer's. They found that women who carry one copy of that gene variant were twice as likely to develop the disease as women without the gene. It is not clear why the gene poses such a drastic increase in risk but may be how the gene interacts with estrogen. (Source: https://www.alzheimers.net/8-12-15-why-is-alzheimers-more-likely-in-women/)

HOPEFUL BREAKTHROUGH: A study of more than 11,000 patients found that technology can detect biological evidence of brain changes clearly linked to Alzheimer's. The study involved people enrolled by nearly 1,000 dementia specialists across the country, and all had been diagnosed with either mildly impaired thinking skills or dementia in the last 2 years. "As in any other field of medicine, a clinical history and a physical exam is very important but being able to directly visualize the biology of the organ involved in the disease process is really essential to make an accurate diagnose," says lead study author Gil Rabinovici, MD, a professor at the University of California, San Francisco's Memory and Aging Center. This study used amyloid positron emission tomography, or PET scans, to detect amyloid plaques in the brain, which all people with Alzheimer's have. Before study participants were scanned, Alzheimer's disease was the leading cause suspected for cognitive impairment in 76.9% of patients, while the PET scans read as positive only for Alzheimer's in 55.3% of patients with mildly impaired thinking skills, and 70.1% of those with dementia. "Our hope is when we complete the second phase of the study, we will be able to show the scan not only changes management but improves outcomes, and that will lead Medicare to reconsider covering scans at least in some situations," Rabinovici says. (Source: https://www.webmd.com/alzheimers/news/20190501/alzheimers-diagnosis-breakthrough-hopeful-expensive)

Wooten’s Medical Mission Trip To Guyana: ‘I Have Been The One Blessed’ Not Patients – Thesummervillenews

Posted on March 2, 2020 by Danzig

By GENE ESPYStaff WriterI cant tell you what a blessing it is, Mrs. Carolyn Parker Wooten said about her medical mission trips.Every place I have been I have left a piece of my heart and I can barely speak about it without choking up and tears coming to my eyes because I see these people living in squalor and they have basically nothing except a cellphone and a television. I went to be a blessing to these people, but I was the one who received the blessing.Carolyn Wooten was born and raised in Trion and graduated at Trion High School a River Rat as she explained.I walked across the street to school every day, Mrs. Wooten said.When she graduated at THS, she went into nursing school and is a Registered Nurse with a Bachelors Degree in Nursing.When she first began her career, medical missions had not come into play yet.Years later, after she had raised her family, a missionary came to the church she and her husband were attending for a mission conference. He was planning a trip to Peru and he said he really needed medical people to with him.It was like God reached out and touched my shoulder and said, He was talking to you.On our way home, I looked over to my husband and I said I have something to tell you, and he said, You want to go to Peru dont you? Mrs. Wooten continued.It was like he already knew, she added.I said, yes, I do, Wooten answered.She didnt know anything about Peru except it was something she felt like she needed to do.Mrs. Wooten met with the missionary and he explained what they did they go into the country as tourists, under the guidance and under the umbrella of a local church with a local pastor.What the Medical Missions does is follow the outline of Matthew 25:31-36.The purpose is to go reach people for their physical needs in order to meet their spiritual needs, Mrs. Wooten explained. I cant tell you what a blessing it is. I went to be a blessing to these people, but I was the one who received the blessing.As a registered nurse, she is recognized in other countries as being a medical provider under the guidance of the team that she is with. They have one doctor and have nurses that are providers.We dont just need medical people, we need people who are willing to give of their time to help set up the clinics, to help rebuild a wall that falls down because most of the countries they go to are Third World countries, Mrs. Wooten said.She said one of the things that she finds in these countries is not brushing your teeth for a week with tap water and using bottled water.When you get in the shower they tell you to be sure to keep your mouth tightly closed and your head down so the water doesnt get up your nose just because of the things that are in that water our bodies are not used to, she continued. I grew up on Trion water and we drank that straight out of the ground.

GUYANAOn the recent trip the group went to Guyana, South America with the Truth for Today Medical Missions.When you think about Guyana, you think about Jim Jones, she added. The people there have not forgotten what happened. There is a lot of gang activity and the worst thing a gang member can call another is a Jonesy Boy.Her group was a small group, they went to five separate areas, doing five clinics in five days.That was a lot of work, you have to set up everything and at the end of the day you take it all down and this involves moving church pews.Most of the clinics were in churches which are metal roofs over cinder block walls and then some very hard seats.The week they were there they saw 90 patients the first day; the second day they saw 69 medical and vision saw 80; the third day they saw 51 medical and 54 in vision; the next day they saw 90 in medical and 125 in vision and the last day they saw 96 in medical and 74 in vision.In the medical area the patients would come in and see Mrs. Wooten or one of the other providers and they would sit down and talk.I would ask, What can I do for you today? What kind of problems are you having? she continued.Most of them are joint pain, back pain and what they call the flu, which is sinus or upper respiratory and we treat them accordingly.They also did a lot of teaching about high blood pressure and diabetes which they have a lot of because of their high carbohydrates diets.We make sure that we get them started on medication so they can continue their medication through their socialized medicine, which is a disaster, Wooten added.Vision is a very big part of the clinics. She said that the Rotary boxes of old gasses, many times end up on a mission trip and many glasses you think are trash or you dont need them anymore, to these people the eyeglasses are a treasure.A billboard the group saw advertised financing for eyeglasses from six months up to two years.To give those people a pair of glasses, they have a machine called a refractor, they check their eyes and go through all the charts and then they know the strengths needed. They then go through the boxes of hundreds and hundreds of glasses and find the strength they need.The look on these peoples faces when they put on their glasses for the first time, they can see and they can read now, Mrs. Wooten said.There is no charge to the patients for the medical or the eyeglasses.Everything is either volunteer or free.She explained that the worst case she saw was a 17-year-old boy who was six foot, eight, and he was very thin. He was educated and still in school, and he was complaining about everything that was textbook for a bad thyroid. He had a goiter and for someone that young that is something that is not a good outcome.Rarely did we see someone that smoked, Mrs. Wooten added.I bring away from my trips how rich, how blessed and how fortunate we are to live in America, Mrs. Wooten said. And to be free and to have the freedoms that we have.

More here:
Wooten's Medical Mission Trip To Guyana: 'I Have Been The One Blessed' Not Patients - Thesummervillenews

Looking to the future with Dr. Francis Collins – Newswise

Posted on March 17, 2020 by Danzig

Newswise What gets the leader of the NIH jazzed?

Speaking to a packed West Pavilion auditorium March 6, Francis Collins, M.D., Ph.D., director of the National Institutes of Health, shared his picks of 10 areas of particular excitement and promise in biomedical research. (Watch the full talk here.)

In nearly every area, UAB scientists are helping to lead the way as Collins himself noted in several cases. At the conclusion of his talk, Collins addedhis advice for young scientists. Here is Collins top 10 list, annotated with some of the UAB work ongoing in each area and ways that faculty, staff and students can get involved.

1. Single-cell sequencing

[see this section of the talk here]

I am so jazzed with what has become possible with the ability to study single cells and see what they are doing, Collins said. They have been out of our reach now we have reached in. Whether you are studying rheumatoid arthritis, diabetes or the brain, you have the chance to ask each cell what it is doing.

Single-cell sequencing and UAB:Collins noted that Robert Carter, M.D., the acting director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, was a longtime faculty member at UAB (serving as director of the Division of Clinical Immunology and Rheumatology). For the past several years, UAB researchers have been studying gene expression in subpopulations of immune cells inpatients with rheumatoid arthritis.

Join in:Researchers can take advantage of the single-cell sequencing core facility in UABsComprehensive Flow Cytometry Core, directed by John Mountz, M.D., Ph.D., Goodwin-Blackburn Research Chair in Immunology and professor in the Department of Medicine Division of Clinical Immunology and Rheumatology.

Learn more:Mountz and other heavy users of single-cell sequencing explain how the techniqueslet them travel back in time and morein this UAB Reporter story.

2. New ways to see the brain

[See this section of the talk here]

The NIHsBRAIN Initiativeis making this the era where we are going to figure out how the brain works all 86 billion neurons between your ears, Collins said. The linchpin of this advance will be the development of tools to identify new brain cell types and circuits that will improve diagnosis, treatment and prevention of autism, schizophrenia, Parkinsons and other neurological conditions, he said.

Brain tech and UAB:Collins highlighted thework of BRAIN Initiative granteeHarrison Walker, M.D., an associate professor in the Department of Neurology, whose lab has been developing a more sophisticated way to understand the benefits of deep brain stimulation for people with Parkinsons and maybe other conditions, Collins said.

Join in:UABs planned new doctoral program in neuroengineering would be the first of its kind in the country.

Learn more:Find out why neuroengineering is asmart career choicein this UAB Reporter story.

3. Induced pluripotent stem (iPS) cells

[See this section of the talk here]

Researchers can now take a blood cell or skin cell and, by adding four magic genes, Collins explained, induce the cells to become stem cells. These induced pluripotent stem (iPS) cells can then in turn be differentiated into any number of different cell types, including nerve cells, heart muscle cells or pancreatic beta cells. The NIH has invested in technology to put iPS-derived cells on specialized tissue chips. Youve got you on a chip, Collins explained. Some of us dream of a day where this might be the best way to figure out whether a drug intervention is going to work for you or youre going to be one of those people that has a bad consequence.

iPS cells at UAB:Collins displayed images of thecutting-edge cardiac tissue chipdeveloped by a UAB team led by Palaniappan Sethu, Ph.D., an associate professor in the Department of Biomedical Engineering and the Division of Cardiovascular Disease. The work allows the development of cardiomyocytes that can be used to study heart failure and other conditions, Collins said.

Join in:UABs biomedical engineering department, one of the leading recipients of NIH funding nationally, is a joint department of the School of Engineering and School of Medicine. Learn more about UABsundergraduate and graduate programs in biomedical engineering, and potential careers, here.

Learn more:See howthis novel bioprinterdeveloped by UAB biomedical researchers is speeding up tissue engineering in this story from UAB News.

4. Microbiome advances

[See this section of the talk here]

We have kind of ignored the fact that we have all these microbes living on us and in us until fairly recently, Collins said. But now it is clear that we are not an organism we are a superorganism formed with the trillions of microbes present in and on our bodies, he said. This microbiome plays a significant role not just in skin and intestinal diseases but much more broadly.

Microbiome at UAB:Collins explained that work led by Casey Morrow, Ph.D., and Casey Weaver, M.D., co-directors of theMicrobiome/Gnotobiotics Shared Facility, has revealed intriguing information abouthow antibiotics affect the gut microbiome. Their approach has potential implications for understanding, preserving and improving health, Collins said.

Join in:Several ongoing clinical trials at UAB are studying the microbiome, including a studymodifying diet to improve gut microbiotaand an investigation of the microbiomes ofpostmenopausal women looking for outcomes and response to estrogen therapy.

Learn more:This UAB News storyexplains the UAB researchthat Collins highlighted.

5. Influenza vaccines

[See this section of the talk here]

Another deadly influenza outbreak is likely in the future, Collins said. What we need is not an influenza vaccine that you have to redesign every year, but something that would actually block influenza viruses, he said. Is that even possible? It just might be.

Influenza research at UAB:Were probably at least a decade away from a universal influenza vaccine. But work ongoing at UAB in the NIH-fundedAntiviral Drug Discovery and Development Center(AD3C), led by Distinguished Professor Richard Whitley, M.D., is focused on such an influenza breakthrough.

Join in:For now, the most important thing you can do to stop the flu is to get a flu vaccination. Employees can schedule afree flu vaccination here.

Learn more:Why get the flu shot? What is it like? How can you disinfect your home after the flu? Get all the information atthis comprehensive sitefrom UAB News.

6. Addiction prevention and treatment of pain

[See this section of the talk here]

The NIH has a role to play in tackling the crisis of opioid addiction and deaths, Collins said. The NIHs Helping to End Addiction Long-term (HEAL) initiative is an all-hands-on-deck effort, he said, involving almost every NIH institute and center, with the goal of uncovering new targets for preventing addiction and improving pain treatment by developing non-addictive pain medicines.

Addiction prevention at UAB:A big part of this initiative involves education to help professionals and the public understand what to do, Collins said. The NIH Centers of Excellence in Pain Education (CoEPE), including one at UAB, are hubs for the development, evaluation and distribution of pain-management curriculum resources to enhance pain education for health care professionals.

Join in:Find out how to tell if you or a loved one has a substance or alcohol use problem, connect with classes and resources or schedule an individualized assessment and treatment through theUAB Medicine Addiction Recovery Program.

Learn more:Discover some of the many ways that UAB faculty and staff aremaking an impact on the opioid crisisin this story from UAB News.

7. Cancer Immunotherapy

[See this section of the talk here]

We are all pretty darn jazzed about whats happened in the past few years in terms of developing a new modality for treating cancer we had surgery, we had radiation, we had chemotherapy, but now weve got immunotherapy, Collins said.

Educating immune system cells to go after cancer in therapies such as CAR-T cell therapy is the hottest science in cancer, he said. I would argue this is a really exciting moment where the oncologists and the immunologists together are doing amazing things.

Immunotherapy at UAB:I had to say something about immunology since Im at UAB given that Max Cooper, whojust got the Lasker Awardfor [his] B and T cell discoveries, was here, Collins said. This is a place I would hope where lots of interesting ideas are going to continue to emerge.

Join in:The ONeal Comprehensive Cancer Center at UAB is participating in a number of clinical trials of immunotherapies.Search the latest trials at the Cancer Centerhere.

Learn more:Luciano Costa, M.D., Ph.D., medical director of clinical trials at the ONeal Cancer Center, discusses the promise ofCAR-T cell therapy in this UAB MedCast podcast.

Assistant Professor Ben Larimer, Ph.D., is pursuing a new kind of PET imaging test that could give clinicians afast, accurate picture of whether immunotherapy is workingfor a patient in this UAB Reporter article.

8. Tapping the potential of precision medicine

[See this section of the talk here]

The All of Us Research Program from NIH aims to enroll a million Americans to move away from the one-size-fits-all approach to medicine and really understand individual differences, Collins said. The program, which launched in 2018 and is already one-third of the way to its enrollment goal, has a prevention rather than a disease treatment approach; it is collecting information on environmental exposures, health practices, diet, exercise and more, in addition to genetics, from those participants.

All of Us at UAB:UAB has been doing a fantastic job of enrolling participants, Collins noted. In fact, the Southern Network of the All of Us Research Program, led by UAB, has consistently been at the top in terms of nationwide enrollment, as School of Medicine Dean Selwyn Vickers, M.D., noted in introducing Collins.

Join in:Sign up forAll of Usat UAB today.

Learn more:UABs success in enrolling participants has led to anew pilot study aimed at increasing participant retention rates.

9. Rare diseases

[See this section of the talk here]

Rare Disease Day, on Feb. 29, brought together hundreds of rare disease research advocates at the NIH, Collins said. NIH needs to play a special role because many diseases are so rare that pharmaceutical companies will not focus on them, he said. We need to find answers that are scalable, so you dont have to come up with a strategy for all 6,500 rare diseases.

Rare diseases at UAB: The Undiagnosed Diseases Network, which includes aUAB siteled by Chief Genomics Officer Bruce Korf, M.D., Ph.D., is a national network that brings together experts in a wide range of conditions to help patients, Collins said.

Participants in theAlabama Genomic Health Initiative, also led by Korf, donate a small blood sample that is tested for the presence of specific genetic variants. Individuals with indications of genetic disease receive whole-genome sequencing. Collins noted that lessons from the AGHI helped guide development of the All of Us Research Program.

Collins also credited UABs Tim Townes, Ph.D., professor emeritus in the Department of Biochemistry and Molecular Genetics, for developing the most significantly accurate model of sickle cell disease in a mouse which has been a great service to the [research] community. UAB is now participating in anexciting clinical trial of a gene-editing technique to treat sickle cellalong with other new targeted therapies for the devastating blood disease.

Join in:In addition to UABs Undiagnosed Diseases Program (which requires a physician referral) and the AGHI, patients and providers can contact theUAB Precision Medicine Institute, led by Director Matt Might, Ph.D. The institute develops precisely targeted treatments based on a patients unique genetic makeup.

Learn more:Discover how UAB experts solved medical puzzles for patients by uncovering anever-before-described mutationandcracking a vomiting mysteryin these UAB News stories.

10. Diversity in the scientific workforce

[See this section of the talk here]

We know that science, like everything else, is more productive when teams are diverse than if they are all looking the same, Collins said. My number one priority as NIH director is to be sure we are doing everything we can to nurture and encourage the best and brightest to join this effort.

Research diversity at UAB:TheNeuroscience Roadmap Scholars Programat UAB, supported by an NIH R25 grant, is designed to enhance engagement and retention of under-represented graduate trainees in the neuroscience workforce. This is one of several UAB initiatives to increased under-represented groups and celebrate diversity. These include several programs from theMinority Health and Health Disparities Research Centerthat support minority students from the undergraduate level to postdocs; thePartnership Research Summer Training Program, which provides undergraduates and especially minority students with the opportunity to work in UAB cancer research labs; theDeans Excellence Award in Diversityin the School of Medicine; and the newly announcedUnderrepresented in Medicine Senior Scholarship Programfor fourth-year medical students.

Join in:The Roadmap program engages career coaches and peer-to-peer mentors to support scholars. To volunteer your expertise, contact Madison Bamman atmdbamman@uab.eduorvisit the program site.

Learn more:Farah Lubin, Ph.D., associate professor in the Department of Neurobiology and co-director of the Roadmap Scholars Program,shares the words and deeds that can save science careersin this Reporter story. In another story, Upender Manne, Ph.D., professor in the Department of Pathology and a senior scientist in the ONeal Comprehensive Cancer Center, explains how students in the Partnership Research Summer Training Program gethooked on cancer research.

Read the rest here:
Looking to the future with Dr. Francis Collins - Newswise

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

Posted on November 4, 2019 by Danzig

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."

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

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

Posted on November 14, 2019 by Danzig

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

How Gene Editing And Pig Organs Can End The Human Transplant Shortage – Newsweek

Posted on August 12, 2017 by Fredricko

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.

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

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

Posted on August 25, 2017 by ev1

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

UCLA Human Genetics

Posted on August 29, 2017 by Fredricko

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

Scientists find new genetic locations for type 2 diabetes – Medical News Today

Posted on May 7, 2017 by Danzig

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.

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

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

Posted on May 15, 2017 by ev1

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)

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

Posted on June 11, 2017 by Danzig

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.

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

OTUD6B gene mutations cause intellectual, physical disability – Baylor College of Medicine News (press release)

Posted on March 27, 2017 by Fredricko

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.

Gene Drive Research in Non-Human Organisms …

Posted on May 5, 2017 by Fredricko

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 transfer cures diabetes in mice without side effect – Next Big Future

Posted on May 6, 2017 by Danzig

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

Scientists Spot Gene for Rare Disorder Causing Deafness, Blindness – Montana Standard

Posted on March 27, 2017 by Fredricko

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.

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

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

Posted on March 27, 2017 by ev1

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)

Working on ‘the human side’ of heritable cancers – Penn: Office of University Communications

Posted on March 2, 2020 by Danzig

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

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

Posted on March 17, 2020 by Danzig

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

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

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

Posted on April 2, 2020 by Danzig

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

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

Posted on February 13, 2020 by Danzig

- 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

Danielle CanteyGlover Park Groupdcantey@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

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