The Multiple System Atrophy (“MSA”) Coalition announces a ground-breaking million-dollar multi-year collaborative project focused on exploring the genetics of up to 1,200 people with either a diagnosis of probable MSA, in the case of living patients, or postmortem pathological confirmation of multiple system atrophy, aimed at locating commonalities in their genes that might contribute to the development of multiple system atrophy. The aim of this collaborative study is to sequence and organize the genomes of existing genetic samples as well as to organize previously sequenced whole-genome data into a single database that is accessible to researchers worldwide. While many researchers have looked at the genetics of MSA, this will be the first time such a large number of genomes from ethnically diverse populations have been sequenced and organized in such a way as to facilitate thorough analysis and collaborative enterprise.

“MSA is not typically passed from parent to child, except in extremely rare cases. However, there are still important clues about the underlying cause of MSA that can be found by examining the genetic code of a large population of MSA patients and looking for commonalities. Because MSA is a such a rare disease, there is a need for multiple researchers to work together and pool their data. Until now there has not been a concerted effort among genetic labs to combine these rare genetic samples from MSA patients with diverse backgrounds into a large, shared database,” said Pam Bower, chair of the MSA Coalition’s research committee. “The MSA Coalition is proud to be the driver of this ground-breaking study.”

University of Florida will perform genetic sequencing under the direction of Matt Farrer, PhD, while storage, analysis and visualization of data will occur at Harvard Medical School in the Clinical Genome Analysis Platform (“CGAP”) under the direction of Dana Vuzman, PhD. Additional genomic information will be provided by University College of London, Queen Square Institute of Neurology under the direction of Henry Houlden, MBBS, MRCP, PhD; by Translational Genomics Research Institute (TGen) under the direction of Matt Huentelman, PhD (Funded in part by the Rex Griswold Foundation, a grant from the NIH NINDS (R21-NS093222, PI: Huentelman), and through institutional support of TGen.); and by Seoul National University, under the direction of Beomseok Jeon, MD, PhD and Han-Joon Kim, MD, PhD. The Core G team also plans to coordinate their work with that being done at NIH under the direction of Sonja Scholz, MD, PhD. The group, collectively known as “Core G” (Genetics), will work closely with Vik Khurana, MD, PhD, board member and Scientific Liaison of the Board of Directors of the MSA Coalition and Chief of the Movement Disorders Division at Brigham and Women’s Hospital and Harvard Medical School. Dr. Khurana will endeavor to integrate Core G team-member efforts more broadly into the MSA Collaborative Cores Initiative™ sponsored by the Coalition that will seed fund additional projects over time.

“I am thrilled that after years of planning and deliberation that Core G is funded and ready to go,” said Khurana. “This group of terrific researchers, together with their expertise, bring precious patient samples from three continents to establish a foundation upon which other collaborations and initiatives will be built. We are under no illusion that the genetics of MSA will prove challenging, no less than a moonshot. At the same time, genetic insights promise to unlock powerful hypothesis-driven science that can find cures. And so, this moonshot is worth the effort and has been structured to be collaborative, open and sustainable in the long-term.”

“We are incredibly proud of assembling this group of world-renowned researchers to collaborate on this project. It has taken almost three years to organize this project and obtain consents from all the institutions involved. Great care has been taken by all contributing institutions to safeguard the privacy of the patients and anonymize the genetic materials, so that patient privacy is protected,” said Cynthia Roemer, MSA Coalition board chair. “We are also grateful to our many donors, who have made this project possible, and to the patients we have lost to MSA who generously left bequests to the MSA Coalition to further critical research like this. We quite literally could not do it without them!”

Dana Vuzman, PhD is an Instructor of Medicine at Harvard Medical School and the Director of Genomic Platform Development at DBMI. Dr. Vuzman oversees the implementation of the Clinical Genome Analysis Platform (CGAP) and the Single Cell RNA Platform in the Department. Prior to joining DBMI, she served as Chief Informatics Officer at One Brave Idea, Sr. Director of Biomedical Informatics at KEW, Inc., and Co-Director at Brigham Genomic Medicine. Dr. Vuzman earned her PhD in Computational Biology from the Weizmann Institute of Science in Israel and completed her postdoctoral training in Computational Genetics at Brigham and Women’s Hospital and Harvard Medical School.

Matt Farrer, PhD is critically acclaimed for his work in the genetics and neuroscience of Parkinson’s disease. His inspiration to apply genetic analysis to complex neurologic disorders came from early work as a care assistant of patients and families with neurologic and psychiatric disorders. Dr. Farrer earned his first degree in Biochemistry with a Doctoral degree in Molecular and Statistical Genetics from St. Mary’s Hospital Medical School, UK. He completed a fellowship in Medical Genetics at the Kennedy-Galton Centre, UK and in Neurogenetics at Mayo Clinic. Dr. Farrer became an Assistant Professor of Molecular Neuroscience in 2000 where he opened his first laboratory to predict and prevent Parkinson’s disease. Dr. Farrer became a tenured professor in 2006, a Mayo Consultant, and subsequently, a Distinguished Mayo Investigator. In 2010, Dr. Farrer was awarded a Canada Excellence Research Chair to build the Centre for Applied Neurogenetics and Neuroscience at the University of British Columbia, Vancouver, Canada where he became a Professor of Medical Genetics. The Province of British Columbia subsequently awarded him the Don Rix Chair in Precision Medicine, and his team had many notable accomplishments including several new genes and mouse models for Parkinson’s disease. The team also implemented high-throughput sequencing in pediatric seizure disorders and neonatology in clinical service. The former was funded through the Medical Services Plan of British Columbia and was a first for Canada.

In 2019, Dr. Farrer accepted an endowed chair at the Norman Fixel Institute for Neurological Diseases (thanks to a generous endowment from the Lauren and Lee Fixel Family Foundation). Dr. Matt Farrer also directs the UF Clinical Genomics Program. As such he currently has appointments and affiliations in the UF College of Medicine’s Neurology and Pathology Departments, Clinical and Translational Science Institute, the Evelyn F. and William L. McKnight Brain Institute, the Center for Translational Research in Neurodegenerative Disease, and the Center for Neurogenetic in addition to the Norman Fixel Institute for Neurological Diseases.

Henry Houlden, MBBS, MRCP, PhD: Dr. Houlden is a professor of neurology and neurogenetics in the Department of Neuromuscular Disease, University College, London, Queen Square Institute of Neurology, and undertakes research laboratory works on neurogenetics and movement disorders with a particular interest in rare diseases that are adult or childhood-onset, such as multiple system atrophy (MSA), spinocerebellar ataxia and other movement disorders, inherited neuromuscular conditions, and difficult to diagnose disorders, particularly in diverse and underrepresented populations. He assists with the integration of new gene discovery with exome and genome sequencing identifying disease genes such as CANVAS, NARS1, NKX-6.2, SCA11, SCA15, GRIA2, and GAD1, with functional experimental validation in human tissue and other model systems. Dr. Houlden has clinical expertise in inherited neurological disorders and movement disorders such as multiple system atrophy, ataxia, leukodystrophy, epilepsy and paroxysmal conditions, spastic paraplegia and neuromuscular conditions.

Matt Huentelman, PhD: Dr. Huentelman’s research interests center around the investigation of the “-omics” (genomics, transcriptomics, and proteomics) of neurological traits and disease. His laboratory’s overarching goal is to leverage findings in these disciplines to better understand, diagnose, and treat human diseases of the nervous system.

Dr. Huentelman joined TGen in July of 2004 after completing his doctoral work at the University of Florida’s Department of Physiology and Functional Genomics at the McKnight Brain Institute where he investigated the application of gene therapy in the study and prevention of hypertension. His undergraduate degree is in Biochemistry from Ohio University’s Department of Chemistry and Biochemistry at Clippinger Laboratories. Dr. Huentelman’s career includes visiting researcher stints in Moscow, Russia at the MV Lomonosov Moscow State University “Biology Faculty” and in the United Kingdom within the University of Bristol’s Department of Physiology.

Beomseok Jeon, MD, PhD: Professor Jeon is the medical director of the Movement Disorder Center, Seoul National University Hospital and is interested in genetics of Parkinsonism and medical and surgical treatment of advanced Parkinson’s Disease.

Dr. Jeon earned his undergraduate, MD and PhD degrees from Seoul National University. His clinical interests include Parkinson’s disease and other movement disorders including tremor, ataxia, dystonia, and chorea. His research focuses on the role of genetics in movement disorders, especially in the Korean population. He has established a DNA bank of thousands of Korean patients with movement disorders and normal controls. He is also involved in treatment of advanced Parkinson disease, and works with neurosurgical colleagues for various surgical treatment.

Han-Joon Kim, MD, PhD: Dr. Kim is a Professor in the Department of Neurology and the Movement Disorder Center at Seoul National University Hospital, Seoul, Korea. After graduation from the Medical College of Seoul National University in 1997, Dr. Kim took an internship and residency in neurology at Seoul National University Hospital (SNUH) where he became a Movement Disorder Specialist.

Clinically, Dr. Kim has experience with patients with various movement disorders including Parkinson’s Disease (PD), Multiple System Atrophy (MSA), other atypical Parkinsonisms, and ataxias. Notably, Dr. Kim has set up a large registry of Korean MSA patients, which will serve as a basis for both observational and interventional studies in this rare disease.

Sonja W. Scholz, MD, PhD: Dr. Scholz is a Neurologist and Neurogeneticist specialized in movement and cognitive disorders. She received her medical degree from the Medical University Innsbruck, Austria. Following graduation, she was a post-doctoral fellow at the Laboratory of Neurogenetics at the NIH’s National Institute on Aging (NIA) under the supervision of Drs. Andrew Singleton and John Hardy. She obtained a Ph.D. in Neurogenomics from the University College London, UK in 2010. She then moved to Baltimore to complete her neurology residency training at Johns Hopkins. In 2015, Dr. Scholz received the McFarland Transition to Independence Award for Neurologist-Scientists. She is a Lasker Clinical Research Tenure Track Investigator within the Neurogenetics Branch at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS). Her laboratory focuses on identifying genetic causes of neurodegenerative diseases, such as dementia with Lewy bodies, multiple system atrophy, and frontotemporal dementia.

# # #

In the video below, Vikram Khurana, Scientific Liaison to the MSA Coalition Board of Directors, Chief of the Division of Movement Disorders at Brigham and Women’s Hospital and Harvard Medical School, announces outcomes of some notable research projects. This presentation was included in the 2021 MSA Coalition Patient & Family Conference.