Scientific Advisory Board

SCIENTIFIC ADVISORY BOARD

Anne B. Young, MD, PhD Chair, Scientific Advisory Board

Chair Emerita, Department of Neurology Massachusetts General Hospital Distinguished Julieanne Dorn Professor of Neurology Harvard Medical School Royal College of Physicians, London American SCIENTIFICAcademy of Arts and Sciences ADVISORYNational Academy of MedicineBOARD

ith funding from the Hereditary Disease Foundation and the National Institutes of Health, Anne WYoung has been involved in Huntington’s disease research for four decades. Anne participated in the Hereditary Disease Foundation’s Venezuela HD Project from 1981 until 2002 when the team could no longer return because of then Venezuelan President Hugo Chavez’s restrictions. In Venezuela, Anne focused on making accurate diagnoses, drawing blood for DNA, taking skin biopsies and helping collect tissue samples generously donated by the Venezuelan HD family members. Of the 20,000 neurological exams performed, Anne did many of them. Anne trained and mentored medical students and residents who joined the team.

Anne and her late husband John B. (“Jack”) Penney, Jr. tested new models of how the basal ganglia controls movements. They based their theories on data from animal and postmortem human brain samples. They discovered, through clever experiments, how the basal ganglia are affected in Huntington’s and Parkinson’s diseases. The basal ganglia controls movement, reward, emotions and memory. Anne and Jack’s model suggested the design of therapies that would help both diseases.

Anne was recruited in 1991 to Harvard Medical School and Massachusetts General Hospital as the hospital’s first female head of a department. She founded and designed the MassGeneral Institute for Neurodegenerative Diseases (MIND) in 2001 to accelerate the discovery of new and effective therapies for these disorders. Anne is a driving force in the Hereditary Disease Foundation’s Scientific Advisory Board which she chairs. She also plays a key role on the Foundation’s Board of Directors as its Vice Chair. She received the HDF’s Leslie Gehry Brenner Prize for Innovation in Science in 2016.

SCIENTIFIC ADVISORY BOARD I met patients with HD when I was doing my PhD and was “ incredibly moved. My passion to find an effective treatment for Huntington’s disease drives everything I do. From “the beginning I have understood the importance of the Hereditary Disease Foundation and its critical role in advancing research towards therapies for HD.

Sarah J. Tabrizi, FRCP, PhD, FMedSci University College London Institute of Neurology

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Anne B. Young, MD, PhD — Chair Diane E. Merry, PhD Massachusetts General Hospital Thomas Jefferson University Harvard Medical School Richard I. Morimoto, PhD Leslie M. Thompson, PhD — Vice Chair Northwestern University University of California, Irvine A. Jennifer Morton, PhD, ScD, FRSB Gillian P. Bates, FMedSci, PhD, FRS University of Cambridge University College London (UCL) Institute of Neurology Richard C. Mulligan, PhD C. Frank Bennett, PhD Harvard Medical School Ionis Pharmaceuticals Harry T. Orr, PhD Yvette Bordelon, MD, PhD University of Minnesota David Geffen School of Medicine at UCLA Henry L. Paulson, MD, PhD Alan Buckler, PhD University of Michigan Triplet Therapeutics, Inc. Christopher E. Pearson, PhD Marie-Françoise Chesselet, MD, PhD The Hospital for Sick Children David Geffen School of Medicine at UCLA University of Toronto, Canada

Beverly L. Davidson, PhD Bernard M. Ravina, MD Children’s Hospital of Philadelphia Praxis Precision Medicine University of Pennsylvania University of Rochester School of Medicine

Steven Finkbeiner, MD, PhD Lynn A. Raymond, MD, PhD, FRCPC Taube/Koret Center for Neurodegenerative Disease University of British Columbia, Canada Gladstone Institutes H. Diana Rosas, MD University of California, San Francisco Massachusetts General Hospital Kenneth H. Fischbeck, MD Harvard Medical School National Institute of Neurological Disorders and Joan A. Steffan, PhD Stroke, National Institutes of Health University of California, Irvine Michelle Gray, PhD Sarah J. Tabrizi, FRCP, PhD, FMedSci University of Alabama at Birmingham University College London (UCL) Institute of Neurology Myriam Heiman, PhD Leslie P. Weiner, MD Massachusetts Institute of Technology University of Southern California Broad Institute of MIT and Harvard Nancy S. Wexler, PhD H. Robert Horvitz, PhD Columbia University Massachusetts Institute of Technology Hereditary Disease Foundation 2002 Nobel laureate Ai Yamamoto, PhD David E. Housman, PhD Columbia University Massachusetts Institute of Technology X. William Yang, MD, PhD Jeffery W. Kelly, PhD David Geffen School of Medicine at UCLA The Skaggs Institute for Chemical Biology The Scripps Research Institute Andrew S. Yoo, PhD Washington University School of Medicine Michael S. Levine, PhD David Geffen School of Medicine at UCLA Scott Zeitlin, PhD University of Virginia School of Medicine John Mazziotta, MD, PhD UCLA Health Sciences SCIENTIFIC ADVISORY BOARD

The Hereditary Disease Foundation’s Scientific Advisory Board is composed of distinguished scientists from around the world. The Board sets the scientific priorities for the Foundation, reviews grant and fellowship applications and selects the most innovative and promising research projects for funding.

Anne B. Young, MD, PhD Chair Scientific Advisory Board

Chair Emerita, Department of Neurology Massachusetts General Hospital Distinguished Julieanne Dorn Professor of Neurology Harvard Medical School Royal College of Physicians, London American Academy of Arts and Sciences National Academy of Medicine

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Leslie M. Thompson, PhD Vice Chair Scientific Advisory Board

Donald Bren and Chancellor’s Professor Department of Psychiatry and Human Behavior Department of Neurobiology and Behavior University of California, Irvine

eslie Thompson has studied Huntington’s disease for most of her scientific career and was a member of the Linternational consortium that identified the causative gene for HD in 1993. Leslie is involved in understanding how the HD mutation causes dysfunction of neurons and other cell types in the brain with the goal of identifying druggable targets. She is also looking at how modifications of the huntingtin (HTT) protein and other cellular molecules are influenced by the mutation. Leslie worked with a group of investigators to establish the HD patient-derived iPS cell consortium (induced pluripotent stem cells). She is using stem cells to study disease and modifiers of disease onset through multi- institutional collaborations and Big Data approaches. Several potential therapeutic approaches have been identified over the years and she is currently evaluating the use of human neural stem cells as a candidate HD therapeutic. She is an American Association for the Advancement of Science fellow and received the HDF’s Leslie Gehry Brenner Prize for Innovation in Science in 2013.

Gillian P. Bates, FMedSci, PhD, FRS

Professor of Molecular Neuroscience Co-Director Huntington’s Disease Centre University College London (UCL) Institute of Neurology Fellow, Royal Society

illian Bates is using mouse models of HD to understand the first events that cause HD, validate approaches Gto treating this disease and steer drug development programs. Gill was part of the Hereditary Disease Foundation-led team that cloned the gene for HD in 1993. She went on to develop the first mouse model of HD in 1996. She received the HDF’s Leslie Gehry Brenner Prize for Innovation in Science in 2012.

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Frank Bennett, PhD

Chief Scientific Officer Ionis Pharmaceuticals

rank Bennett is responsible for preclinical antisense drug discovery and antisense technology research. He Fis one of the founding members of Ionis Pharmaceuticals. Frank has been involved in the development of antisense oligonucleotides as therapeutic agents, including research on the application of oligonucleotides for inflammatory, neurodegenerative diseases and cancer, oligonucleotide delivery, pharmacokinetics and medicinal chemistry. He has published more than 230 papers in the field of antisense research and development and has more than 175 issued U.S. patents. Prior to joining Ionis, Frank was Associate Senior Investigator in the Department of Molecular Pharmacology at SmithKline and French Laboratories, currently, GlaxoSmithKline. He received his PhD in Pharmacology from Baylor College of Medicine, Houston, Texas and his BS degree in Pharmacy from the University of New Mexico, Albuquerque, New Mexico. He performed his postdoctoral research in the Department of Molecular Pharmacology at SmithKline and French Laboratories. Frank received HDF’s 2018 Leslie Gehry Brenner Prize for Innovation in Science and the 2019 Breakthrough Prize in Life Sciences.

Yvette Bordelon, MD, PhD

Clinical Professor Department of Neurology David Geffen School of Medicine at UCLA

vette Bordelon’s clinical work involves the diagnosis and treatment of Parkinson’s disease, Huntington’s Ydisease and other movement disorders. Her clinical research interests include the development of biomarkers for neurodegenerative diseases and conducting clinical trials in movement disorders.

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Alan J. Buckler, PhD

Chief Scientific Officer Triplet Therapeutics, Inc.

lan is a seasoned drug discovery leader with over 25 years of research experience in industry and Aacademia. In August 2020, he joined Triplet Therapeutics, Inc., a company focused on discovery and development of therapies to treat repeat expansion disorders, as Chief Scientific Officer.

Previously, he served as Chief Scientific Officer of Scholar Rock, Inc., where he was responsible for research, preclinical development, and manufacturing of the company’s novel antibody-based therapeutics. Prior to joining Scholar Rock, Alan held senior level research positions in Biogen and Novartis, where he led both target validation and drug discovery efforts for multiple therapeutic modalities. Prior to Novartis, Alan served as the Chief Scientific Officer of Ardais Corporation and as Vice President of Molecular Genetics at Sequana Therapeutics/Axys Pharmaceuticals.

Prior to joining industry, Alan served on the Neurology faculty of Massachusetts General Hospital and Harvard Medical School, where his collaborative focus was on the genetics of cancer and rare diseases, including Huntington’s disease and Myotonic Dystrophy. Alan received his AB in Biology from the University of Chicago, PhD in Microbiology from the Boston University School of Medicine and completed his post-doctoral training at the Center for Cancer Research, Massachusetts Institute of Technology.

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Marie-Françoise Chesselet, MD, PhD

Emeritus Distinguished Professor of Neurology and Neurobiology Emeritus Charles H. Markham Professor of Neurology David Geffen School of Medicine at UCLA

fter receiving her MD and PhD degrees in Paris, France, Marie-Françoise held research positions in France, Aand faculty positions at the Medical College of Pennsylvania and the University of Pennsylvania before joining UCLA in 1996. At UCLA, she chaired the Department of Neurobiology (2002-2013) and was Interim Chair of the Department of Neurology (2015-2016). She directed the Center for the Study of Parkinson’s Disease, the National Institute of Neurological Disorders and Stroke (NINDS)-funded UCLA Udall Center for Parkinson’s Disease Research, the National Institute of Environmental Health Sciences-funded UCLA Center for Gene Environment in Parkinson’s Disease, and the UCLA Advanced Center for Parkinson’s Disease Research of the American Parkinson Disease Association.

Marie-Françoise has directed graduate programs at the University of Pennsylvania and UCLA and the NINDS- funded Training Program in Neural Repair from 1998 to 2014. Until her retirement in 2016, her laboratory conducted research on the molecular mechanisms of disorders of the basal ganglia and new treatments for Parkinson’s and Huntington’s diseases. Her work has been supported by the National Institutes of Health, the Department of Defense, the Hereditary Disease Foundation, the Michael J. Fox Foundation, Cure HD Initiative, CIRM, and several philanthropic and biopharmaceutical companies. She has served on the National Advisory Environmental Health Sciences Council and the Science Advisory Boards of the American Parkinson Disease Association, the Michael J. Fox Foundation, and the Restless Legs Syndrome Foundation. She is a Fellow of the American Association for the Advancement of Science, former Chair and current Secretary of its section on Neuroscience. Currently, she is the President of the World Parkinson Coalition, and a member of several scientific review committees and a consultant for philanthropic and biotech companies.

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Beverly L. Davidson, PhD

Director of The Raymond G. Perelman Center for Cellular and Molecular Therapeutics Chief Scientific Strategy Officer Arthur V. Meigs Chair in Pediatrics Children’s Hospital of Philadelphia Professor of Pathology and Laboratory Medicine Perelman School of Medicine University of Pennsylvania American Academy of Arts and Sciences National Academy of Medicine

everly Davidson’s research is focused on inherited genetic diseases that cause central nervous system Bdysfunction, with a focus on (1) recessive, childhood onset neurodegenerative disease, in particular the lysosomal storage diseases such as the Mucopolysaccharidoses and Batten’s disease; and (2) dominant genetic diseases; for example, the CAG repeat disorders (Huntington’s disease and Spinocerebellar ataxia), and (3) understanding how noncoding RNAs participate in neural development and neurodegenerative disease processes. Her research is focused on experiments to better understand the biochemistry and cell biology of these disorders, and to develop gene and small molecule based medicines for therapy.

Recent honors include the 2009 Mathilde Solowey Award (NIH), the 2011 J.J. Armond Lecturer (American Association of Neuropathologists), the 2011 Presidential Lecture (University of Iowa), member of Scientific Advisory Board of the Hereditary Disease Foundation (2006-2009 and 2012-present); the 2014 Chair, Electorate Nominating Committee, Medical Sciences Section, American Association for the Advancement of Science, appointed to the National Advisory Council, National Institute of Neurological Disorders and Stroke (2014-2018). In 2015 Bev was awarded HDF’s Leslie Gehry Brenner Prize for Innovation in Science, and was appointed to the Scientific Advisory Boards of the Huntington Study Group and the Medical Research Advisory Board of the National Ataxia Foundation. In 2017 she was elected to the American Academy of Arts and Sciences, was appointed a member of the International Selection Committee for the 2018 Bower Award and Prize for Achievement in Science at the Franklin Institute, received the F.E. Bennett Memorial Lectureship Award (American Neurological Association) and was invited to join the Packard Center Board of Advisors at Johns Hopkins University. In March 2019 Bev chaired the Gordon Research Conference on Lysosomal Storage Diseases. In April 2019 she was elected Vice President of the Board of Directors for the American Society of Gene and Cell Therapy (ASGCT), the largest association of individuals involved in gene and cell therapy research, and is now President-Elect of ASGCT. Also in 2019, Bev was elected to the National Academy of Medicine.

Bev is a co-founder of Spark Therapeutics, Spirovant Sciences, and Saliogen Therapeutics, and serves on the Scientific Advisory Boards of Sarepta Therapeutics, Intellia Therapeutics, Prevail Therapeutics, Panorama Medicines, Pfizer TSAP, Voyager Therapeutics, National Resilience Bio and Homology Medicines. She received her BS in Biology from the Nebraska Wesleyan University, and her PhD in Biological Chemistry from the University of Michigan.

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Steven Finkbeiner, MD, PhD

Director, Center for Systems and Therapeutics Director, Taube/Koret Center for Neurodegenerative Disease Gladstone Institutes Professor, Departments of Neurology and Physiology University of California, San Francisco

teven Finkbeiner is interested in understanding mechanisms of neurodegenerative disease and developing Stherapeutic strategies and therapies. He has studied HD since 1998, applying innovative methods and tools to understand its causes and to find treatments, including robotic microscopy, stem cells and artificial intelligence. With philanthropists in the San Francisco Bay Area, he established the Taube-Koret Center, which works to develop the most promising discoveries from the labs into therapeutics, often in partnership with drug companies. His most promising HD therapeutics program stimulates a pathway in cells that helps clear the abnormal Huntingtin protein.

Kenneth H. Fischbeck, MD

Chief, Neurogenetics Branch National Institute of Neurological Disorders and Stroke National Institutes of Health National Academy of Medicine

enneth Fischbeck received AB and AM degrees from Harvard University and an MD degree from Johns KHopkins. After a medical internship at Case Western Reserve University and a neurology residency at the University of California, San Francisco, he did postdoctoral research on muscular dystrophy at the University of Pennsylvania. In 1982 he joined the faculty in the Neurology Department at the University of Pennsylvania Medical School. In 1998 he came to the National Institute of Neurological Disorders and Stroke as Chief of the Neurogenetics Branch. He received the Cotzias Award from the American Academy of Neurology and the Jacoby Award from the American Neurological Association. His research group is identifying the causes and studying the mechanisms of hereditary neurological and neuromuscular diseases with the goal of developing effective treatment for these disorders.

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Michelle Gray, PhD

Associate Professor Dixon Scholar in Neuroscience Center for Neurodegeneration and Experimental Therapeutics Department of Neurology University of Alabama at Birmingham

ichelle Gray completed her doctoral training in developmental neurobiology at Ohio State University. MHer postdoctoral training was performed with X. William Yang at the University of California Los Angeles where they developed a conditional Bacterial Artificial Chromosome human mutant Huntingtin expressing (BACHD) mouse model.

Michelle is now the Dixon Scholar in Neuroscience and a member of the Center for Neurodegeneration and Experimental Therapeutics at UAB where her lab has a specific interest in the role of mutant Huntingtin expressing astrocytes in the pathogenesis of Huntington’s disease. The lab has identified that astrocytes are key

contributions to the progression of Huntington’s disease-like phenotypes using the conditional BACHD model as well as a differential role of gliotransmission on behavior using this model. A current focus of the lab is understanding the astrocyte and interneuron interactions in the striatum that contribute to the pathogenesis of Huntington’s disease. Momentum always begins with a moment. “ There have been many moments of discovery for the Hereditary Disease Foundation. Now we are on the cusp of another “extraordinary moment—the discovery of a way to push Huntington’s disease beyond the human life span.

Lesley Stahl, “60 Minutes” Correspondent

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Myriam Heiman, PhD

Latham Family Career Development Associate Professor of Neuroscience Department of Brain and Cognitive Sciences Massachusetts Institute of Technology Member, Picower Institute for Learning and Memory Core Member, Broad Institute of MIT and Harvard

yriam Heiman and her lab use mouse and cell models to understand why some cells are more or less Mvulnerable to the mutant HD gene, and use knowledge of these intrinsic differences to identify new therapeutic targets for HD. Myriam was involved in the development of a powerful cell type-specific profiling methodology with Nobel laureate Paul Greengard and Nathaniel Heintz (Translating Ribosome Affinity Purification), and recently developed a novel genetic screening platform for the brain, tools that she is applying to the study of HD.

H. Robert Horvitz, PhD

Investigator, Howard Hughes Medical Institute Professor of Biology Massachusetts Institute of Technology Nobel Laureate National Academy of Sciences American Academy of Arts and Sciences National Academy of Medicine

obert Horvitz, 2002 Nobel Laureate in Physiology or Medicine, is interested in how genes control animal Rdevelopment and behavior and affect human health. Bob has made seminal discoveries concerning the genetic regulation of signal transduction and programmed cell death. By using the experimentally tractable roundworm Caenorhabditis elegans as an experimental organism, he and his team have identified key genes involved in cell lineage, cell fate, cell signaling and programmed cell death as well as in nervous system development and function. They have identified and analyzed molecular and cellular pathways responsible for these and other important biological processes. Their goals are to understand fundamental aspects of biology and to provide mechanistic insights into human diseases, including cancer and neurodegenerative disorders.

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David E. Housman, PhD

Ludwig Professor of Biology Massachusetts Institute of Technology National Academy of Sciences National Academy of Medicine

avid Housman guided the search that led to the discovery of the very first DNA marker ever for a genetic Ddisease. He then led a group of brilliant scientists to find the Huntington’s disease gene itself.

David uses genetic approaches to develop effective strategies for intervention in human disease. His current research focuses on identifying modifier genes which are responsible for variation in age of onset for HD. Prospective studies on extended HD families demonstrate that, other than the length of the CAG repeat sequence, modifier genes contribute significantly to determining the age of onset for HD. David and his lab are currently pursuing genetic linkage and association studies designed to identify these genes. In parallel, he is carrying out studies to identify genes which contribute to the timing of disease onset in mouse model systems for HD. His lab continues to focus on the identification and development of small molecules which show promise for therapeutic intervention in HD.

David received both his BA and PhD from Brandeis University. He received the MIT Science Council Teaching Prize in 1992 and has been honored with the National Biotechnology Award from the National Conference on Biotechnology Ventures. He is a Fellow of the American Association for the Advancement of Science and the American Academy of Microbiology. He is a co-founder of Genzyme Genetics and former Somatix Therapy Corp. and co-founded Kenna Technologies in 2000 and serves as its Advisor. He founded Integrated Genetics in 1980, which was acquired by Genzyme in 1989. He has served as Chairman, Scientific Founder, and Principal Scientific Advisor of Variagenics Inc. since 1993.

David was first recipient of the Hereditary Disease Foundation’s Leslie Gehry Brenner Prize for Innovation in Science in 2010.

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Jeffery W. Kelly, PhD

Lita Annenberg Hazen Professor of Chemistry Department of Chemistry The Skaggs Institute for Chemical Biology The Scripps Research Institute American Academy of Arts and Sciences

effery Kelly discovered the first regulatory-agency-approved drug (tafamidis vyndaqel; Pfizer) that slows the Jprogression of the neurodegenerative disease familial amyloid polyneuropathy and the cardiac disease senile systemic amyloidosis, both caused by the aggregation of the protein transthyretin.

Currently his lab is focused on the discovery of first-in-class drugs that would slow the progression of multiple neurodegenerative diseases by modulating organismal protein homeostasis (e.g. autophagy) and/or neuroinflammation. Jeff has published over 350 scientific papers and has placed 45 trainees in tenured or tenure-track academic positions and 60 former coworkers in biotechnology and pharmaceutical positions.

Important discoveries often start small but seeding key ideas with funds to start exploring can have a huge impact on outcomes. “ The collaboration between the Keck Foundation and the Hereditary “Disease Foundation began with the saga of a group of gene hunters determined to track down the cause of this devastating disease and find a cure. Thanks to four Keck Foundation grants totaling $2,075,000, the search for a cure is underway.

W. M. Keck Foundation Annual Report

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Michael S. Levine, PhD

Vice Chancellor for Academic Personnel Distinguished Professor of Psychiatry and Biobehavioral Sciences David Geffen School of Medicine at UCLA

ichael Levine’s laboratory focuses on the neurophysiological mechanisms underlying neurodegenerative Mdisorders. His multi-disciplinary work carries implications for disorders such as Huntington’s and Parkinson’s diseases and pediatric epilepsy. He has published over 250 peer-reviewed research reports as well as more than 30 book chapters. He has received research support from a variety of agencies within the National Institutes of Health, as well as from the California Institute for Regenerative Medicine, the Office of Naval Research, the HDF, Cure Huntington’s Disease Initiative and numerous other foundations.

Mike is a fellow of the American Association for the Advancement of Science and he received the National Association for Research on Schizophrenia and Depression’s Distinguished Investigator Award in 1999. He also received the UCLA Neuroscience Undergraduate Society’s Excellence in Teaching Award twice, the Department of Psychiatry and Biobehavioral Sciences Undergraduate Teaching Award and the UCLA Council of Advisors’ Outstanding Advisor Award.

He held the Gail Patrick Endowed Chair in Brain Research and was the Associate Director for Education of the Brain Research Institute. He has served as the Department of Psychiatry and Biobehavioral Sciences’ Associate Chair for Academic Affairs, the Special Assistant to two Vice Chancellors for Academic Personnel, Chair of the Undergraduate Interdepartmental Program in Neuroscience, Chair of the Interdepartmental PhD Program in Neuroscience, and Associate Director of the Intellectual and Developmental Disabilities Research Center.

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John Mazziotta, MD, PhD

Vice Chancellor, UCLA Health Sciences CEO, UCLA Health National Academy of Medicine

ohn Mazziotta is recognized as one of the world’s foremost experts on brain imaging. He also was the Jprincipal investigator of the International Consortium for Brain Mapping, leading a world-wide effort to create the first atlas of the human brain, including behavioral, demographic, imaging and genetic data.

Diane E. Merry, PhD

Professor and Vice Chair Department of Biochemistry and Molecular Biology Thomas Jefferson University

iane Merry and her group focus their research on the molecular mechanisms underlying inherited Dneurodegenerative disease, with a primary focus on Kennedy’s disease, which is caused by the identical and unusual genetic mutation that causes Huntington’s disease. Diane’s group has developed and utilized unique cell and mouse models to both understand mechanisms of disease and identify molecular targets for therapeutic development. Over the past decades her group has made important and fundamental discoveries into the structural and functional requirements of the mutant androgen receptor (AR) protein in disease and has identified several AR targets that are in preclinical development.

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Richard I. Morimoto, PhD

Bill and Gayle Cook Professor of Biology Department of Molecular Biosciences Director, Rice Institute for Biomedical Research Northwestern University American Academy of Arts and Sciences

ichard Morimoto focuses his research on the heat shock response. He also studies the function of molecular Rchaperones and the proteostasis network to maintain cellular health and organismal health, and to respond to challenges from environmental and physiological stress, aging and diseases of protein conformation including Alzheimer’s disease, Parkinson’s disease, ALS and Huntington’s disease. Rick has received numerous awards including the National Institutes of Health MERIT Award twice and the Huntington’s Award for Excellence in Medicine from the Huntington’s Disease Society of America. He is a co- founder of Proteostasis Therapeutics, Inc., a biopharmaceutical company in Cambridge, MA, whose goal is to discover small molecule therapeutics for diseases of protein conformation.

Jennifer Morton, PhD, ScD, FRSB

Professor of Neurobiology University of Cambridge Professorial Fellow Director of Studies in Medicine and Veterinary Medicine Newnham College, Cambridge

enny Morton has been working on Huntington’s disease ever since she set up her laboratory at the University Jof Cambridge in 1991. She is interested in understanding the relationship between neurodegeneration and the neurological symptoms in HD. She is particularly interested in sleep, circadian and cognitive decline in HD. With funding from the Hereditary Disease Foundation, The Wellcome Trust, and CHDI Inc., she has characterized the behavioral profile of a number of mouse models of HD. For the past 10 years Jenny has also been working with the HD sheep. She believes that, although it is an unconventional model, there is much to be gained from understanding the behavioral pathology in this large-brained diurnal model of HD. Her lab’s goal is to identify quantifiable readouts of behavior that can be used to test the efficacy of novel therapies for HD.

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Richard C. Mulligan, PhD

Director, Harvard Gene Therapy Initiative Laboratory of Molecular Medicine Mallinckrodt Professor of Genetics Children’s Hospital Harvard Medical School

ichard Mulligan is an internationally recognized pioneer in the development of new technologies for Rtransferring genes into mammalian cells. Scientists use the specialized tools created in his laboratory to unravel basic questions about human development and to devise new therapies for the treatment of both inherited diseases and acquired diseases.

Harry T. Orr, PhD

James Schindler and Bob Allison Ataxia Chair in Translational Research Professor, Department of Laboratory Medicine and Pathology Director, Institute for Translational Neuroscience University of Minnesota National Academy of Medicine

arry Orr received a BA degree from Oakland University in Rochester, Michigan. He earned his PhD at HWashington University, completed a postdoctoral fellowship at Harvard, and joined the University of Minnesota faculty in 1981. His group has a long-standing and productive National Institute of Neurological Disorders and Stroke-supported research program on the use of genetics, biochemical, and behavioral approaches in the study of neurodegeneration with a focus on the human disease spinocerebellar ataxia type 1 (SCA1). In collaboration with Huda Zoghbi at Baylor, they cloned the gene affected in SCA1 - the first genetically defined ataxia. They went on to establish the first transgenic mouse model of a polyglutamine disease. This model is the center of continued studies on the normal function of the gene product, ataxin-1 as well as the SCA1 pathogenic process. The work is among the first to indicate that regions/residues outside of the polyQ tract are critical for disease. Identification of molecular pathways involved in neurodegenerative disease can be a significant aspect in development of efficacious targets for intervention. A current focus is on two signaling pathways each having distinct but seminal roles in SCA1. 17 SCIENTIFIC ADVISORY BOARD

Henry L. Paulson, MD, PhD

Lucile Groff Professor Department of Neurology University of Michigan Health System National Academy of Medicine

enry Paulson explores the reasons why the aging brain degenerates in various neurodegenerative diseases. HHis research focuses on Huntington’s disease, Spinocerebellar Ataxia type 3 and several other inherited

ataxias, as well as Alzheimer’s disease and related protein conformational disorders. He pursues both basic studies of disease mechanisms and translational studies in hopes that his research will lead to therapies for these fatal diseases. The Hereditary Disease Foundation provides a unique “ opportunity to engage and enroll scientists with varying backgrounds and research focus, towards a common “ goal – to understand and develop therapies for HD!

Beverly L. Davidson, PhD Children’s Hospital of Philadelphia University of Pennsylvania

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Christopher E. Pearson, PhD

Senior Scientist Program of Genetics & Genome Biology The Hospital for Sick Children Full-Professor Department of Molecular Genetics University of Toronto, Canada Research Chair in Disease-Associated Genome Instability

hristopher Pearson obtained his PhD at McGill University in Experimental Medicine and did a postdoctorate Cin the Houston Texas Medical Centre during a time when repeat diseases were first being discovered. Since 1993 he has studied the mechanisms of disease-causing repeat instability associated with neurological, neurodegenerative and neuromuscular disease, with the goal of developing treatments by targeting the disease- causing repeat expansions. His lifetime goal is to treat repeat diseases by arresting or reversing somatic CAG expansions.

His lab works on molecular, cellular, and mouse models, and patient tissues of Huntington’s disease, myotonic dystrophy, various spinocerebellar ataxias, fragile X mental retardation, and C9orf72-associated amyotrophic lateral sclerosis. Focus is on DNA repair, DNA damage, epigenetics, and unusual DNA structures formed by the repeats. Recent advances include identifying repeat expansions associated with autism, as well as identifying the first small-molecule to induce contractions of the expanded CAG repeat in the striatum of HD mice.

Christopher was a Scholar of the Medical Research Council of Canada; Member of the Canadian Genetic Disease Network, and is a Canada Research Chair in Disease-Associated Genome Instability. He serves on scientific advisory boards for numerous venture capital companies, National Fragile X Foundation USA, National Ataxia Foundation USA, International Myotonic Dystrophy Consortium, among others. He is Associate Editor for PLoS Genetics, Journal of Medical Genetics, and Human Genetics.

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Bernard Ravina, MD, MSCE

Chief Medical Officer Praxis Precision Medicine Adjunct Professor of Neurology University of Rochester School of Medicine

ernard Ravina’s career has focused on therapeutics development in neurodegenerative and neuropsychiatric

Bdisorders. He has over 20 years of clinical research and therapeutics development experience in government, academia, and industry. Prior to working in the biotechnology industry, Bernard was an Investigator in the Neurogenetics Branch at the National Institute of Neurological Disorders and Stroke, and Associate Professor of Neurology and Vice Chair of Neurology at the University of Rochester School of

Medicine. In biotechnology, Bernard was a Director of Clinical Development at Biogen and Chief Medical

Officer at Voyager Therapeutics. He holds an MD from the Johns Hopkins University School of Medicine and a Masters in Clinical Epidemiology and Biostatistics from the University of Pennsylvania, where he completed residency training in neurology and a fellowship in movement disorders. Bernard is the author of more than

120 scientific publications and serves on multiple foundation and biotechnology scientific advisory boards. “

The Hereditary Disease Foundation has encouraged and facilitated collaborative research among Huntington’s disease researchers across the globe, “creating an environment of close scientific interactions. Leslie M. Thompson, PhD University of California, Irvine

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Lynn A. Raymond, MD, PhD, FRCPC

Director, Djavad Mowafaghian Centre for Brain Health Professor, Department of Psychiatry, Faculty of Medicine Louise A. Brown Chair in Neuroscience Associate Member, Department of Medicine, Division of Neurology Associate Member, Department of Cellular and Physiological Sciences University of British Columbia, Canada

ynn Raymond is a clinician-scientist who trained at Albert Einstein College of Medicine in New York and L completed a Neurology residency and fellowship at the Johns Hopkins Medical Institutions. She was then recruited to the University of British Columbia in 1994 where she combines neuroscience research with clinical practice in Neurology. She leads a Canadian Institutes of Health Research (CIHR) funded research lab and is Clinic Director of the Centre for Huntington Disease.

For many years she has investigated roles of altered neuronal circuits, synapses and NMDA-type glutamate receptors in Huntington’s disease. More recently, her work focuses on changes in cortical and striatal synaptic plasticity and circuit function that may underlie early cognitive and sensorimotor deficits, and could contribute to neuronal vulnerability to degeneration. She has served as UBC site investigator for several multi-centre clinical research studies in Huntington’s disease. Currently, she serves as Director of the Djavad Mowafaghian Centre for Brain Health at UBC.

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DIANA ROSAS

Associate Professor, Departments of Neurology and Radiology Director, Center for Neuro-imaging of Aging and Neurodegenerative Disease Massachusetts General Hospital, Harvard Medical School

iana Rosas is passionately committed to the field of HD research. As a medical resident, she was invited to Djoin the U.S.–Venezuela Collaborative Research Project directed by Dr. Nancy Wexler and sponsored by Dr. Anne Young, chairperson of Neurology at Massachusetts General Hospital at the time. It was a life-altering experience as she saw firsthand the ravages of HD and the tremendous impact it has on families. Diana also realized that much can be done to help families in need. She has been working with families and patients with HD ever since. She feels it is a privilege to care for patients with HD, to be involved in cutting-edge research, and to participate in clinical therapeutic trials. The advances in our knowledge about HD give her great hope that we will be able to find a cure.

Diana was involved in PRECREST, the first clinical trial to enroll presymptomatic and at-risk for HD individuals with a design that allowed trial participants to remain unaware of their genetic status. PRECREST has great relevance to prevention trials being considered for other neurodegenerative diseases as PRECREST established an important precedent in looking at incorporating individuals at genetic risk in a clinical trial rather than only known gene carriers. Diana thinks it is worth considering this approach in future trials because there are limited numbers of individuals who choose to be tested. This would expand the size of the pool of individuals who would participate in a clinical trial. Most people at risk don’t want to know their genetic status and we have to ask if participating in a relatively short-term Phase II study is worth the risk of knowing to those individuals.

In her research, Diana and her team have focused primarily on the development of biomarkers for use in the study of neurodegenerative diseases. She and her team have begun to develop models that may explain clinically heterogeneous phenotypes and variability in disease progression. The current models for both disease prediction and prediction of disease progression are insensitive and inaccurate. They plan to expand their efforts to include several different types of imaging approaches that promise more precise measurements and may provide novel and important information on the neural underpinnings of HD and their clinical consequences.

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Joan S. Steffan, PhD

Associate Professor Department of Psychiatry and Human Behavior University of California, Irvine

oan Steffan is studying how a reduction in cellular housekeeping in the brain may contribute to the onset Jand progression of Huntington’s disease. Joan identified a role for the Huntingtin protein in a process called autophagy which is a mechanism of protein and organelle clearance by the lysosome, an organelle which contains enzymes that degrade cellular trash to keep the cell clean and generate energy during stressful conditions. She is studying how cellular stress pathways turn on autophagy and induce modification of the Huntingtin protein to activate its autophagic function.

Joan has found that modification of the Huntingtin protein becomes impaired with mutation, and that Huntingtin protein levels decline with aging in the part of the brain that is impacted in Huntington’s disease. She continues to evaluate whether a loss of Huntingtin function in autophagy with aging and mutation may contribute to Huntington’s disease pathogenesis, and is working to develop therapies that may activate this function with the hopes of slowing disease progression.

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Sarah J. Tabrizi, FRCP, PhD, FMedSci

Professor of Clinical Neurology Honorary Consultant Neurologist Director, University College London (UCL), Institute of Neurology Joint Head of Department of Neurodegenerative Disease UK Dementia Research Institute at UCL UCL Queen Square Institute of Neurology National Hospital for Neurology and Neurosurgery Queen Square

arah Tabrizi is Director of the UCL Huntington’s Disease (HD) Centre, Joint Head of Department SNeurodegenerative Disease at the UCL Queen Square Institute of Neurology, a Principal Investigator at the UK Dementia Research Institute, and Consultant Neurologist at the National Hospital for Neurology and Neurosurgery. In addition to a basic bench science programme focussing on basic cellular mechanisms of neurodegeneration in HD that can be harnessed for therapeutics, she also leads a large translational research programme that is working towards finding effective disease-modifying treatments for HD. She was global clinical PI on the world’s first gene targeting study for HD using anti-sense oligonucleotide therapy. Sarah was elected as a Fellow of the UK Academy of Medical Sciences in 2014. She was the 2017 recipient of the HDF’s Leslie Gehry Brenner Prize for Innovation in Science. In 2018 she received the Cotzias Award from the Spanish Society of Neurology, and in 2019 the Yahr Award at the World Congress for Neurology and the Alexander Morison Medal from the Royal College of Physicians of Edinburgh.

Leslie P. Weiner, MD

Professor Molecular Microbiology & Immunology, Neurology Richard Angus Grant, Sr., Chair in Neurology Keck School of Medicine University of Southern California

eslie Weiner and his lab have focused on the maturation of neural stem cells, and they have also begun Lto test mutant activated protein C, a molecule that has anti-inflammatory properties as well as being neuroprotective. They will see if it affects brain inflammation, an important factor in HD.

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Nancy S. Wexler, PhD

Higgins Professor of Neuropsychology Columbia University President, Hereditary Disease Foundation 2019 Double Helix Medal 1993 Albert Lasker Public Service Award Royal College of Physicians, London American Academy of Arts and Sciences National Academy of Medicine

ancy Wexler is searching for genes that can push out the onset of Huntington’s disease well beyond our Nlife spans, to age 100 or more. This research is based on genetic material collected from the world’s largest HD family in Venezuela. Nancy led the history-making Venezuela Project, developing a family tree of over 18,000 individuals spanning 10 generations.

This work led to the discovery of the DNA marker for Huntington’s disease in 1983 and the HD gene itself in 1993. This same genetic material has assisted in the mapping of other disease genes, including those responsible for familial Alzheimer’s disease, kidney cancer, two kinds of neurofibromatosis, Lou Gehrig’s disease (ALS), dwarfism and others. One important result of this work was the development of a genetic test to determine if an individual carries the fatal gene.

Nancy has received numerous honors and awards, most recently the 2019 Cold Spring Harbor Laboratory’s Double Helix Medal, and the 2019 New York Academy of Medicine Medal for Distinguished Contributions in Biomedical Science. In 2016, she was the recipient of the inaugural Hermann J. Muller Award for Contributions to Our Understanding of Genes and Society from Indiana University, Bloomington, and the Benjamin Franklin Medal in Life Science in 2007. In 2020, HDF established the Nancy S. Wexler Young Investigator Prize to be awarded annually to researchers whose work reflects the highest caliber of excellence, diligence and creative thinking.

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Ai Yamamoto, PhD

Associate Professor of Neurology Columbia University

i Yamamoto completed her undergraduate education at Massachusetts Institute of Technology in Material’s

AScience and Education in 1994, and went on to Columbia University to complete her doctoral training in 2001. During her dissertation work (with Dr. Rene Hen), she and her colleague Jose Lucas used inducible mouse genetics to demonstrate that the behavioral deficits and neuropathology, such as protein aggregates, associated with Huntington’s disease required continued expression of the disease-causing transgene.

After completing her postdoctoral training, Ai established her lab at Columbia University and has since focused her work on defining the key cellular events that contribute to disease pathogenesis to inform therapeutic approaches. She is the recipient of HDF’s 2020 Leslie Gehry Brenner Prize for Innovation in Science. The Hereditary Disease Foundation has long driven major “ pioneering discoveries in the field of Huntington’s disease. Its workshops and other programs promoting the research that led to these discoveries “have had an immense and far broader impact, for example helping enable the Human Genome Project both intellectually and experimentally.

H. Robert Horvitz, PhD Nobel Laureate Howard Hughes Medical Institute Massachusetts Institute of Technology 26 SCIENTIFIC ADVISORY BOARD

X. William Yang, MD, PhD

Professor Terry Semel Chair in Alzheimer’s Disease Research and Treatment Center for Neurobehavioral Genetics The Jane and Terry Semel Institute for Neuroscience & Human Behavior Department of Psychiatry & Biobehavioral Sciences Brain Research Institute David Geffen School of Medicine at UCLA

illiam Yang completed his undergraduate education at Yale University, obtaining combined BS/MS Wdegrees from the Department of Molecular Biophysics & Biochemistry in 1991. He then completed MD/ PhD training at Rockefeller University (PhD, 1998) and Weill Medical College of Cornell University (MD, 2000).

He co-invented with Nathaniel Heintz a powerful mouse genetic technology to engineer Bacterial Artificial Chromosomes (BACs) and to generate BAC transgenic mice. William’s laboratory, established at UCLA in 2002, has made significant contributions to the development of novel human genomic BAC transgenic mouse models for human neurodegenerative disorders including Huntington’s, Parkinson’s and Alzheimer’s, and the use of such models to dissect disease mechanisms and identify therapeutic targets.

The Yang lab has also applied novel genetic and systems biology approaches to study brain gene expression, and to decipher in vivo RNA and protein networks for HD. They study the role of basal ganglia circuitry in the generation of normal and pathological behaviors. Recently, the Yang lab invented a new mouse genetic tool (called MORF mice) for brainwide genetic sparse labeling of thousands of neurons and glial cells to illuminate their exquisite morphology. William is a recipient of BRAIN Initiative Award from the National Institutes of Health, Brain Disorder Award from the McKnight Foundation, the HDF’s Leslie Gehry Brenner Prize for Innovation in Science in 2014, and is a member of the American Society for Clinical Investigation.

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Andrew S. Yoo, Phd

Associate Professor Department of Developmental Biology Washington University School of Medicine

ndrew Yoo obtained his PhD at Columbia University, where he studied how Notch signaling controls cell fate decisions Ain C. elegans. During his postdoctoral training at Stanford University, Andrew investigated microRNA-mediated genetic pathways that control the BAF chromatin remodeling complex activity during neural development. Andrew’s laboratory investigates mechanisms underlying neurogenic properties of microRNAs and leverages their findings to devise cellular reprogramming approaches that generate specific, disease-relevant subtypes of human neurons by directly converting non- neural somatic cells. Andrew’s team recently established a patient neuron-based platform to model adult-onset pathology of Huntington’s disease (HD), and investigates molecular underpinning of HD pathology and other late-onset neurodegenerative disorders. Andrew’s awards for his work on cellular reprogramming and neurogenesis include NIH Director’s New Innovator Award and the Presidential Early Career Award for Scientists and Engineers from the White House.

Scott Zeitlin, PhD

Associate Professor of Neuroscience University of Virginia School of Medicine

cott Zeitlin is using mouse models to understand the structure and function of the Huntington’s disease protein and to help Sdevelop new therapeutic strategies for this devastating disorder. Using knock-out, conditional knock-out, and protein domain deletion mutations within the normal and mutant Huntingtin proteins, Scott and his collaborators are studying how parts of the normal Huntingtin protein contribute to its function and modulate HD pathogenesis. Scott’s laboratory has also developed mouse models with regulatable normal and abnormal HD genes that are being used to understand the mechanism of HD pathogenesis. Scott’s mice are now the most widely used model by scientists worldwide to discover drugs that could be used to treat Huntington’s disease. Scott was the 2019 recipient of the HDF’s Leslie Gehry Brenner Prize for Innovation in Science.

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