Category Archives: Genetic Medicine

More than 250,000 participants in Pennsylvania and New Jersey have enrolled in Geisingers groundbreaking precision medicine project, MyCode. With DNA sequence and health data currently available on 145,000 of these participants, MyCode is the largest study of its kind in the world.

The program has the potential to help nearly 1,500 people who are at increased risk for potentially life-threatening conditions. Results will allow patients to work with their care providers to prevent or detect disease in its early stages, leading to better health outcomes.

Geisinger has reached a major milestone in precision health, said David H. Ledbetter, Ph.D., executive vice president and chief scientific officer for Geisinger and one of the principal investigators of the MyCode study. This number of enrolled participants speaks to the trust that our community has in Geisingers expertise and the ability we have through this project to make precision health accessible to all of our patients.

MyCode analyzes DNA samples to look for genes known to increase the risk of developing 35 specific health conditions. These include the BRCA1 and BRCA2 genes known to increase risk for breast and ovarian cancer; as well as genes for familial hypercholesterolemia, which can cause early heart attacks and strokes; Lynch syndrome, which can cause early colon, uterine and other cancers; and several heart conditions, including cardiomyopathy and arrythmia.

The project has also identified several genes that can contribute to the development of cognitive disorders. While not always medically actionable, these results can provide valuable information to patients about probable genetic causes for neuropsychiatric conditions like epilepsy, bipolar disorder and depression, as well as learning disabilities and other similar conditions.

There are a lot of genes that have medical actionability, like finding a change in a gene that causes breast cancer and doing more frequent mammograms as a result, said Christa Martin, Ph.D., associate chief scientific officer and one of the principal investigators of the MyCode study. But there are other ones that might not be medically actionable but could have important implications to patients. So, one of our research projects is exploring reporting information back to individuals who have certain brain conditions.

When given the option to receive test results that included genetic changes that could explain their brain condition, more than 90 percent of patients responded in favor of receiving the results. The majority found the information personally useful to explain medical diagnoses they had been dealing with most of their lives.

Giving these patients a unifying medical explanation for their multiple, apparently unrelated learning, behavioral and psychiatric conditions had a powerful impact on these patients and their family members, Dr. Ledbetter said.

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DNA project will aid in early disease detection - Reading Eagle

Last year left us with this piece of bombshell news: He Jiankui, the mastermind behind the CRISPR babies scandal, has been sentenced to three years in prison for violating Chinese laws on scientific research and medical management. Two of his colleagues also face prison for genetically engineering human embryos that eventually became the worlds first CRISPRd babies.

The story isnt over: at least one other scientist is eagerly following Hes footsteps in creating gene-edited humans, although he stresses that he wont implant any engineered embryos until receiving regulatory approval.

Biotech stories are rarely this dramatic. But as gene editing tools and assisted reproductive technologies increase in safety and precision, were bound to see ever more mind-bending headlines. Add in a dose of deep learning for drug discovery and synthetic biology, and its fair to say were getting closer to reshaping biology from the ground upboth ourselves and other living creatures around us.

Here are two stories in biotech were keeping our eyes on. Although successes likely wont come to fruition this year (sorry), these futuristic projects may be closer to reality than you think.

The idea of human-animal chimeras immediately triggers ethical aversion, but the dream of engineering replacement human organs in other animals is gaining momentum.

There are two main ways to do this. The slightly less ethically-fraught idea is to grow a fleet of pigs with heavily CRISPRd organs to make them more human-like. It sounds crazy, but scientists have already successfully transplanted pig hearts into baboonsa stand-in for people with heart failurewith some recipients living up to 180 days before they were euthanized. Despite having foreign hearts, the baboons were healthy and acted like their normal buoyant selves post-op.

But for cross-species transplantation, or xenotransplants to work in humans, we need to deal with PERVsa group of nasty pig genes scattered across the porcine genome, remnants of ancient viral infections that can tag along and potentially infect unsuspecting human recipients.

Theres plenty of progress here too: back in 2017 scientists at eGenesis, a startup spun off from Dr. George Churchs lab, used CRISPR to make PERV-free pig cells that eventually became PERV-free piglets after cloning. Then last month, eGenesis reported the birth of Pig3.0, the worlds most CRISPRd animal to further increase organ compatibility. These PERV-free genetic wonders had three pig genes that stimulate immunorejection removed, and nine brand new human genes to make themin theorymore compatible with human physiology. When raised to adulthood, pig3.0 could reproduce and pass on their genetic edits.

Although only a first clinical propotype that needs further validation and refinement, eGenesis is hopeful. According to one (perhaps overzealous) estimate, the first pig-to-human xenotranplant clinical trial could come in just two years.

The more ethically-challenged idea is to grow human organs directly inside other animalsin other words, engineer human-animal hybrid embryos and bring them to term. This approach marries two ethically uncomfortable technologies, germline editing and hybrids, into one solution that has many wondering if these engineered animals may somehow receive a dose of humanness by accident during development. What if, for example, human donor cells end up migrating to the hybrid animals brain?

Nevertheless, this year scientists at the University of Tokyo are planning to grow human tissue in rodent and pig embryos and transplant those hybrids into surrogates for further development. For now, bringing the embryos to term is completely out of the question. But the line between humans and other animals will only be further blurred in 2020, and scientists have begun debating a new label, substantially human, for living organisms that are mainly human in characteristicsbut not completely so.

With over 800 gene therapy trials in the running and several in mature stages, well likely see a leap in new gene medicine approvals and growth in CAR-T spheres. For now, although transformative, the three approved gene therapies have had lackluster market results, spurring some to ponder whether companies may cut down on investment.

The research community, however, is going strong, with a curious bifurcating trend emerging. Let me explain.

Genetic medicine, a grab-bag term for treatments that directly change genes or their expression, is usually an off-the-shelf solution. Cell therapies, such as the blood cancer breakthrough CAR-T, are extremely personalized in that a patients own immune cells are genetically enhanced. But the true power of genetic medicine lies in its potential for hyper-personalization, especially when it comes to rare genetic disorders. In contrast, CAR-Ts broader success may eventually rely on its ability to become one-size-fits-all.

One example of hyper-tailored gene medicine success is the harrowing story of Mila, a six-year-old with Batten disease, a neurodegenerative genetic disorder that is always fatal and was previously untreatable. Thanks to remarkable efforts from multiple teams, however, in just over a year scientists developed a new experimental therapy tailored to her unique genetic mutation. Since receiving the drug, Milas condition improved significantly.

Milas case is a proof-of-concept of the power of N=1 genetic medicine. Its unclear whether other children also carry her particular mutationBatten has more than a dozen different variants, each stemming from different genetic miscodingor if anyone else would ever benefit from the treatment.

For now, monumental costs and other necessary resources make it impossible to pull off similar feats for a broader population. This is a shame, because inherited diseases rarely have a single genetic cause. But costs for genome mapping and DNA synthesis are rapidly declining. Were starting to better understand how mutations lead to varied disorders. And with multiple gene medicines, such as antisense oligonucleotides (ASOs) finally making a comeback after 40 years, its not hard to envision a new era of hyper-personalized genetic treatments, especially for rare diseases.

In contrast, the path forward for CAR-T is to strip its personalization. Both FDA-approved CAR-T therapies require doctors to collect a patients own immune T cells, preserved and shipped to a manufacturer, genetically engineered to boost their cancer-hunting abilities, and infused back into patients. Each cycle is a race against the cancer clock, requiring about three to four weeks to manufacture. Shipping and labor costs further drive up the treatments price tag to hundreds of thousands of dollars per treatment.

These considerable problems have pushed scientists to actively research off-the-shelf CAR-T therapies, which can be made from healthy donor cells in giant batches and cryopreserved. The main stumbling block is immunorejection: engineered cells from donors can cause life-threatening immune problems, or be completely eliminated by the cancer patients immune system and lose efficacy.

The good news? Promising results are coming soon. One idea is to use T cells from umbilical cord blood, which are less likely to generate an immune response. Another is to engineer T cells from induced pluripotent stem cells (iPSC)mature cells returned back to a young, stem-like state. A patients skin cells, for example, could be made into iPSCs that constantly renew themselves, and only pushed to develop into cancer-fighting T cells when needed.

Yet another idea is to use gene editing to delete proteins on T cells that can trigger an immune responsethe first clinical trials with this approach are already underway. With at least nine different off-the-shelf CAR-T in early human trials, well likely see movement in industrialized CAR-T this year.

Theres lots of other stories in biotech we here at Singularity Hub are watching. For example, the use of AI in drug discovery, after years of hype, may finally meet its reckoning. That is, can the technology actually speed up the arduous process of finding new drug targets or the design of new drugs?

Another potentially game-changing story is that of Biogens Alzheimers drug candidate, which reported contradicting results last year but was still submitted to the FDA. If approved, itll be the first drug to slow cognitive decline in a decade. And of course, theres always the potential for another mind-breaking technological leap (or stumble?) thats hard to predict.

In other words: we cant wait to bring you new stories from biotechs cutting edge in 2020.

Image Credit: Image by Konstantin Kolosov from Pixabay

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The Top Biotech Trends We'll Be Watching in 2020 - Singularity Hub

Michigan Gov. Gretchen Whitmer appointed a number of faculty members and alumni of the Wayne State University School of Medicine to several state boards overseeing medicine and medical licensing.

Appointments to the Michigan Board of Medicine, which works with the Department of Licensing and Regulatory Affairs to oversee the practice of medical doctors ascertaining minimal entry-level competency of medical doctors and requiring continuing medical education during licensure include:

Bryan Little, M.D., Class of 1998, is the specialist in chief of Orthopedic Surgery at the Detroit Medical Center. The governor also appointed Dr. Little to the Michigan Task Force on Physicians Assistants. That entity works with the Department of Licensing and Regulatory affairs to oversee the practice of physicians assistants. The terms of both appointments expire Dec. 31, 2023.

Angela Trepanier, M.S., CGC, professor of Molecular Medicine and Genetics and director of the Genetic Counseling Masters Program at the School of Medicine. She will represent genetic counselors during her term, which expires Dec. 31, 2023.

Donald Tynes, M.D., Class of 1995, clinical assistant professor for the School of Medicine and chief medical officer of the Benton Harbor Health Center, will serve a term through Dec. 31, 2023.

Hsin Wang, M.D., Class of 1999, was appointed to the Michigan Board of Licensed Midwifery, which works with the Department of Licensing and Regulatory Affairs to establish and implement the licensure program for the practice of midwifery in the state. Dr. Wang is an obstetrician-gynecologist with the Detroit Medical Center and the director of the Pelvic Health Program for DMC Huron Valley-Sinai Hospital. Her term runs through Dec. 31, 2023.

Melissa Mafiah, M.D., Class of 2014, was appointed to the Michigan Board of Occupational Therapists for a term that expires Dec. 31, 2023. Dr. Mafiah is a physical medicine and rehabilitation physician at W.H. Beaumont Hospital. The board works with the Department of Licensing and Regulatory Affairs to promulgate rules for licensing occupational therapists and ascertaining minimal entry level competency of occupational therapists and occupational therapy assistants.

Michael Dunn, M.D., chief of Medicine at the Henry Ford West Bloomfield Hospital and the senior staff physician for the hospitals Pulmonary and Critical Care Medicine Division, is an assistant clinical professor of Medicine for the School of Medicine. He was appointed to the Michigan Board of Respiratory Care, which oversees the licensure requirements and standards for respiratory therapists. His appointment runs through Dec. 31, 2023.

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Faculty and alumni appointed to state medical boards - The South End

BETHESDA, Md., Jan. 7, 2020 /PRNewswire/ --The second annual Medical Genetics Awareness Week will be celebrated March 17-21, 2020. Through Medical Genetics Awareness Week, the American College of Medical Genetics and Genomics (ACMG) aims to promote awareness of the importance of medical genetics professionals, including medical geneticists, laboratory geneticists, genetic counselors, nurses and physician assistants, on the healthcare team. The theme of Medical Genetics Awareness Week is "Celebrating the Contributions of the Entire Medical Genetics Team to Patient Care."

New for 2020 are dedicated medical genetics awareness web pages available at http://www.acmg.net/medicalgeneticsawareness. These pages offer a wide range of resources including tips on how to become an ambassador for medical genetics in your workplace and community; a resource tool kit with suggestions for medical genetics-related activities and tools for use on social media; and information on careers in medical genetics.

Medical Genetics Awareness Week is celebrated to recognize the invaluable contributions that medical genetics healthcare professionals make in the diagnosis, management and prevention of genetic diseases, and the difference these professionals make in the lives of patients and families. Medical Genetics Awareness Week is also intended to educate other healthcare professionals, students and trainees on who medical geneticists are, how they are trained and what they do in the clinic and laboratory.

"As medical genetics and genomics finds a home in healthcare systems across the country, remember the valuable role that the medical and laboratory geneticist plays in delivering high quality high value care," said Anthony R. Gregg, MD, MBA, FACOG, FACMG. "Some in our community have more than 10 years of laboratory and/or clinical training after college. Our disciplines attract the "best in class." As we speak with and care for our patients, we are reminded that it is a privilege to be a part of the medical genetics teama team that includes care providers across the clinical spectrum."

Events related to Medical Genetics Awareness Week will be held during the ACMG Annual Clinical Genetics Meeting in San Antonio, Texas (www.acmgmeeting.net) March 17-21, 2020. The ACMG Annual Meeting is the largest conference specifically for clinical geneticists in the United States. Those interested in collaborating with ACMG to celebrate Medical Genetics Awareness Week, holding their own event or becoming an "ambassador" for medical genetics are invited to email rsantos@acmg.net for more information.

"As a practicing clinical geneticist I have been working with individuals dealing with a genetic issue in their family for over three decades," said Maximilian Muenke, MD, FACMG, ACMG'schief executive officer. "It has been a privilege to meet and accompany families over the years and learn from their challenges and how many of them grow in the process. Even though the overall numbers of healthcare professionals in medical genetics have grown, the demand for genetics services has grown even faster. Based on the preliminary data analysis of the NCC Medical Genetics Workforce Survey, a study initiated by the American College of Medical Genetics and Genomics, wait times to make an appointment with a medical geneticist are too long in many parts of the US. It is my hope that the Medical Genetics Awareness Week will increase knowledge of our profession in the general population and compassion for those affected by genetic conditions."

In 2019, the first ever Medical Genetics Awareness Week brought together people from across the globe to raise awareness of the important work of medical geneticists. The success of the 2020 celebration will once again rest on the participation of people everywhere. ACMG invites you to help 2020's celebration set new records for engagement by visiting the new Medical Genetics Awareness Week web pages and using the resources and tools we offer to support your celebrations. Be sure to tag @TheACMG on social media and include the following hashtags in your social media posts related to Medical Genetics Awareness Week:

#MedicalGeneticsAwareness#IamaMedicalGeneticist#FutureGeneticsProfessional#IamaLabGeneticist#IamaGeneticCounselor#IamaNurseinGenetics#IamaGeneticsPA

About the American College of Medical Genetics and Genomics (ACMG) and ACMG Foundation

Founded in 1991, the American College of Medical Genetics and Genomics (ACMG) is the only nationally recognized medical society dedicated to improving health through the clinical practice of medical genetics and genomics and the only medical specialty society in the US that represents the full spectrum of medical genetics disciplines in a single organization. The ACMG is the largest membership organization specifically for medical geneticists, providing education, resources and a voice for more than 2,300 clinical and laboratory geneticists, genetic counselors and other healthcare professionals, nearly 80% of whom are board certified in the medical genetics specialties. ACMG's mission is to improve health through the clinical and laboratory practice of medical genetics as well as through advocacy, education and clinical research, and to guide the safe and effective integration of genetics and genomics into all of medicine and healthcare, resulting in improved personal and public health. Four overarching strategies guide ACMG's work: 1) to reinforce and expand ACMG's position as the leader and prominent authority in the field of medical genetics and genomics, including clinical research, while educating the medical community on the significant role that genetics and genomics will continue to play in understanding, preventing, treating and curing disease; 2) to secure and expand the professional workforce for medical genetics and genomics; 3) to advocate for the specialty; and 4) to provide best-in-class education to members and nonmembers. Genetics in Medicine, published monthly, is the official ACMG journal. ACMG's website (www.acmg.net) offers resources including policy statements, practice guidelines, educational programs and a 'Find a Genetic Service' tool. The educational and public health programs of the ACMG are dependent upon charitable gifts from corporations, foundations and individuals through the ACMG Foundation for Genetic and Genomic Medicine.

Kathy Moran, MBAkmoran@acmg.net

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SOURCE American College of Medical Genetics and Genomics

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Second Annual Medical Genetics Awareness Week Will Be Celebrated March 17-21, 2020 - P&T Community

Puzzling injury: Some children who carry variants in a gene called ZNF292 have injured blood vessels in their brains.

Mutations in a gene called ZNF292 lead to a variety of developmental conditions, including autism and intellectual disability, according to a new study1.

ZNF292 encodes a protein that influences the expression of other genes. It is highly expressed in the developing human brain, particularly in the cerebellum, an area that controls voluntary movement and contributes to cognition. However, its function in neurodevelopment is unknown.

Scientists first linked ZNF292 to intellectual disability in a 2012 study. A 2018 analysis of five ZNF292 variants tied the gene to autism, but the work was preliminary2.

In the new study, researchers identified 28 people who have mutations in ZNF292. The participants come from six countries and are between 10 months and 24 years old. The group carries a total of 24 mutations in the gene, 23 of which are spontaneous meaning that they were not inherited from a parent.

The sheer number of families and children that have been identified so far has been quite high, says Ghayda Mirzaa, lead investigator and assistant professor of genetic medicine at Seattle Childrens Hospital in Washington.

All but one of the participants have intellectual disability. In total, 17 of the participants are suspected or confirmed to have autism and 9 are suspected or confirmed to have attention deficit hyperactivity disorder. All but two have speech delays, and four have had language regression or are minimally verbal.

Mirzaas team found an additional 15 people with mutations in the gene from 12 families. However, the data from these people were incomplete, so the researchers had to exclude them from the analysis. The team has connected with at least 10 other mutation carriers in the six weeks since the study was published in Genetics in Medicine.

The researchers have used their data to classify a new condition. However, it may be premature to call it a syndromic form of autism or intellectual disability, says Holly Stessman, assistant professor of pharmacology and neuroscience at Creighton University in Omaha, Nebraska, who was not involved in the work.

People with ZNF292 variants have a broad spectrum of physical traits. For instance, 11 of the people in the study have growth abnormalities such as short stature; 10 have low muscle tone; and 3 have stiff or mixed muscle tone. The researchers had access to magnetic resonance imaging scans for 17 of the participants: 9 show brain abnormalities such as atypically shaped regions, and 3 of those 9 appear to have blood-vessel injuries in the brain.

Nearly half of the participants also have unusual facial characteristics, including an undersized jaw or eyes that are unusually far apart. Vision problems, such as involuntary eye movement or crossed eyes, affect nine people in the group. Less common facial differences include prominent incisors and protruding ears.

Autism genes are often linked to a wide range of characteristics, says Santhosh Girirajan, associate professor of biochemistry and molecular biology at Pennsylvania State University, who was not involved in the study. Variability has become the rule now, rather than the exception, he says.

Mirzaa says her group plans to study more individuals with variants in ZNF292, and to investigate the genes function.

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Study ties gene active in developing brain to autism - Spectrum

Astellas Pharma recentlyagreed to acquire Audentes Therapeutics, a move it expects will result in faster development of potentially best-in-class therapies for rare neuromuscular diseases, including muscular dystrophy (MD).

Audentes vectorized exon-skipping technology which uses a modified adeno-associated virus (AAV) vector to allow cells to skip over mutated sections of genes will complement Astellas own work, Kenji Yasukawa, president and CEO of Astellas, said in a press release.

Recent scientific and technological advances in genetic medicine have advanced the potential to deliver unprecedented and sustained value to patients, and even to curing diseases with a single intervention, Yasukawa said.

Audentes has developed a robust pipeline of promising product candidates which are complementary to our existing pipeline, including its lead program AT132, he added. By joining together with Audentes talented team, we are establishing a leading position in the field of gene therapy with the goal of addressing the unmet needs of patients living with serious, rare diseases.

The technology uses the modified AAV vector to deliver small molecules antisense oligonucleotides complementary to the RNA sequence of a gene of interest, which allow cells to skip over mutated exons while they are producing proteins.

Exons are the coding regions of genes that provide instructions to make proteins.

Audentes had started developing several therapies for Duchenne muscular dystrophy (DMD) based on its exon-skipping technology. These include AT702, AT751 and AT753.

All three treatment candidates use the same AAV delivery vector. However, as they target different DMD gene exons, the potential therapies are intended for distinct subgroups of patients. AT702 is designed to skip exon 2 and is meant for those who either have duplications in exon 2 or mutations in exons 1-5. AT751 is designed for those with mutations in exon 51, and AT753 for people with alterations in exon 53.

Audentes had also started developing and testing AT466, an experimental treatment for myotonic dystrophy type 1.

The acquisition also gives Astellas direct access to AT132, Audentes lead gene therapy candidate for the treatment ofX-linked myotubular myopathy.

AT132 uses an AAV8 viral vector to deliver a functional copy of the MTM1 gene to muscle cells. This enables the production of myotubularin, an important enzyme for the development and maintenance of muscle cells.

Matthew R. Patterson, chairman and CEO of Audentes, said his company is very pleased with the agreement. With its focus on innovative science and a global network of research, development and commercialization resources, we believe that operating as part of the Astellas organization optimally positions us to advance our pipeline programs and serve our patients, he said.

Under the terms of the agreement, Audentes will become an independent subsidiary of Astellas and will have access to scientific resources to accelerate the development and manufacturing of the combined product pipeline. The transaction, worth $3 billion, is expected to take place early this year.

Joana is currently completing her PhD in Biomedicine and Clinical Research at Universidade de Lisboa. She also holds a BSc in Biology and an MSc in Evolutionary and Developmental Biology from Universidade de Lisboa. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells cells that make up the lining of blood vessels found in the umbilical cord of newborns.

Total Posts: 42

Jos is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimers disease.

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New MD Treatments the Main Goal of Astellas, Audentes Merger - Muscular Dystrophy News