Genetic Strategies To Treat The Epilepsies Workshop

Elizabeth Berry-Kravis MD, Ph.D. is a Professor of Pediatrics and Neurological Sciences at Rush University Medical Center in Chicago. She established the Fragile X Clinic and Research Program in 1991, through which she has provided care to over 800 patients with fragile X syndrome (FXS). She has studied medical issues, epilepsy and psychopharmacology in FXS, and has been a leader in translational research in FXS for 20 years, including development of clinical outcome measures and biomarkers, natural history studies, newborn screening, and particularly clinical trials of new targeted treatments in FXS, for which she has been PI or Co-PI of 27 trials, both industry and investigator sponsored. Her laboratory studies the cellular role of fragile X mental retardation protein (FMRP), relationship between FMRP and clinical function, and optimization of genetic testing methods. More recently she has expanded clinical and translational work to other neurodevelopmental disorders in addition to FXS, including autism spectrum disorders and single gene models of ASD, including Phelan McDermid syndrome, Rett syndrome, and Angelman syndrome. She also is working on translational research in rare neurogenetic disorders including Niemann-Pick type C, Battens disease, pantothenate kinase-associated neurodegeneration, and creatine transporter deficiency, as well as N-of-1 trials of ASOs and gene therapy for early onset epileptic encephalopathies and other neurogenetic conditions. She is on Advisory and/or Review Boards for the FRAXA Research Foundation, National Fragile X Foundation, Phelan McDermid Syndrome Foundation, International Rett Syndrome Foundation, Angelman Syndrome Foundation, Foundation for Angelman Syndrome Therapeutics, Combined Brain, N=1 Collaborative, n-Lorem Foundation and the GATHER Foundation. She has received the NFXF Jarrett Cole Clinical Award, FRAXA Champion Award, NFXF William and Enid Rosen Research Award, March of Dimes Jonas Salk Research Award, American Academy of Neurology Sidney Carter Award in Child Neurology, John Merck Fund Sparkplug Award, the FRAXA Ingenuity Award, the FAST Innovation Award, and the inaugural Martha Bridge Denckla Award from the Child Neurology Society for work in cognitive disorders of children.

Dr. Gaia Colasante earned her Master’s degree in Biotechnology from the University of Milan and her Ph.D. in Neuroscience and Molecular Medicine from Vita-Salute San Raffaele University, conducting research under the supervision of Dr. Vania Broccoli. Her focus was on forebrain development, particularly investigating the role of the transcription factor Arx in these processes. This interest led her to the laboratory of Professor Jeffrey Golden at the Children’s Hospital of Philadelphia, where she continued her research on the role of Arx in GABAergic interneuronal migration using time-lapse imaging techniques.

Upon returning to San Raffaele Hospital, she shifted her focus to cellular reprogramming. She defined a cocktail of transcription factors capable of converting fibroblasts and pluripotent stem cells into GABAergic interneurons, aiming to provide a cell source for cell replacement therapies in epilepsy. More recently, she has employed the CRISPR/dCas9 activator strategy to enhance the regulation of therapeutic genes in both genetic and non-genetic forms of epilepsy.

Dr. Colasante currently serves as a project leader at San Raffaele Hospital, where she a oversees a research team dedicated to investigate mechanisms underlying Dravet Syndrome and related neurodevelopment disorders and to the development of gene therapy for their treatment. She has recently become a member of the International League Against Epilepsy Advanced Gene Therapies Task Force and joined the scientific advisory board of the Dravet Syndrome Foundation.

Beverly L. Davidson, Ph.D. is the Director, Raymond G. Perelman Center for Cellular and Molecular Therapeutics, Chief Scientific Strategy Officer, and holds the Katherine A. High Chair in Cell and Gene Therapy at Children’s Hospital of Philadelphia. She is Professor of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania. She received her Ph.D. in Biological Chemistry from University of Michigan.

The Davidson lab is focused on genetic diseases that affect the brain, including how mutant gene products contribute to disease, and why certain brain regions are more susceptible. The team employs advanced molecular methods, sequencing and imaging modalities in animal models, and uses a variety of molecular tools to test various hypotheses. The lab is also engaged in the development of next generation therapeutics for inherited disorders, including the engineering of novel gene therapy vector capsids and cargo to approach tissue and cell type specific treatments.

Recent honors include election into the American Academy of Arts and Sciences and the National Academy of Medicine, the Hereditary Disease Foundation’s Leslie Gehry Brenner Prize for Innovation in Science, recipient of the Transformative Research Award from the Hereditary Disease Foundation (shared with Drs. L. Thompson and J-H Cha), and the recipient of the Dr. John W. Schut Research Achievement Award from the National Ataxia Foundation. Dr. Davidson is the past president of the American Society of Gene and Cell Therapy.

Dr. Hazlett is a psychologist with over twenty years of experience in child neuropsychology and neurodevelopmental disorders. She is on the faculty in the Department of Psychiatry at UNC-Chapel Hill and at the Carolina Institute for Developmental Disorders. Dr. Hazlett’s primary research is focused on learning about brain development in autism and other neurodevelopmental disorders. Dr. Hazlett uses measures from brain MRI scans and psychological assessments to test relationships between brain and cognition. Dr. Hazlett leads several projects using neuroimaging to study the brain development in autism spectrum disorder, Angelman syndrome, and Down syndrome (and led a completed study of fragile X syndrome). She has been involved in the NIH funded “Baby Connectome” Project (BCP) where she oversaw the behavioral phenotyping at the UNC site and coordinated efforts with the UMN team as co-director for the BCP behavioral core. Dr. Hazlett is currently involved in the NIH funded National Brain Gene Registry and leads the development and implementation of the behavioral phenotyping. She also serves as a behavioral consultant (‘behavioral navigator’) to UNC’s Intellectual and Developmental Disability Research Center (IDDRC). Dr. Hazlett has co-authored over 100 peer-reviewed research articles and has authored numerous book chapters. In addition to her research activities, Dr. Hazlett is a board licensed psychologist who spends her clinical time in a pediatric neuropsychology clinic, a diagnostic clinic for autism spectrum disorders, and a multi-disciplinary for neurogenetic syndromes.

Dr. Katherine High trained in internal medicine, hematology, and molecular genetics. Her pioneering bench-to-bedside studies of gene therapy for hemophilia led to a series of basic and clinical investigations that characterized the human immune response to AAV gene delivery vectors. A long-time member of the faculty of the Perelman School of Medicine of the University of Pennsylvania, she was also an Investigator of the Howard Hughes Medical Institute at the Children’s Hospital of Philadelphia. In 2013 she co-founded Spark Therapeutics, which she joined full-time as President and Chief Scientific Officer in 2014. At Spark she led the team that achieved the first FDA approval of a gene therapy for genetic disease, Luxturna, for a congenital form of blindness, and also led the successful Phase 1/2 studies for Beqvez, now an approved gene therapy for hemophilia B. Spark Therapeutics was acquired by Roche in 2019. Dr. High is an elected member of the National Academy of Medicine, the Royal College of Physicians (London), and the National Academy of Sciences. Currently she is a Visiting Professor at Rockefeller University, and an Advisor to GV (formerly Google Ventures).

Mary Anne Meskis is a founding member and the Executive Director of the Dravet Syndrome Foundation (DSF). She is a passionate advocate for the Dravet syndrome and rare epilepsy communities. Since her son’s diagnosis in 2004, she has actively participated in numerous working groups and industry advisory panels. Under her leadership, DSF has prioritized research, along with fostering patient community engagement and education. Currently, she resides in western North Carolina with her husband and the youngest of her three children, Elliot, who has Dravet syndrome.