Gene Therapy: A Conversation With Drs Benke & Ultragenyx

Panelist

Heather Lau, M.D. M.S. is a board-certified neurologist with special qualifications in child neurology and recently joined Ultragenyx as Executive Director of Global Clinical Development, where she will lead efforts to develop new therapies for a range of neurologic diseases. Dr. Lau received her bachelor of science with honors from Cornell University and a master of science in biochemistry and molecular biology from New York Medical College. She went on to receive her doctorate of medicine from the University of Rochester. She trained in pediatrics at Montefiore Medical Center and completed her child neurology training as well as additional fellowship training in Neurogenetics from New York University. Dr. Lau was assistant professor in Child Neurology at NYU School of Medicine and had been the Director of the NYU Lysosomal Storage Disorders Program at NYU Langone Health for 8 years and associate director of the Division of Neurogenetics. She maintained a large and diverse practice of patients with rare, inherited disorders of the nervous system with a special interest in lysosomal storage disorders, ataxias, and leukodystrophies. Dr. Lau is now an adjunct assistant professor at Yale University in the Department of Internal Medicine continuing her efforts in rare disease research. Throughout her academic career, Dr. Lau had been actively engaged in clinical research and a principal investigator for over 40 clinical interventional trials and disease registries evaluating enzyme replacement therapies, small molecules, and gene therapy.

Sharyl Fyffe-Maricich Ph.D.: Executive Director of Molecular and Cell Biology Research at Ultragenyx Pharmaceutical. Dr. Sharyl Fyffe-Maricich received a BS degree from Queen’s University in Canada, and a PhD in Human and Molecular Genetics from Baylor College of Medicine. She completed her graduate training in the lab of Dr. Huda Zoghbi where she studied the contribution of specific neuronal subpopulations to the underlying biology of Rett Syndrome. Following her postdoctoral training at Case Western Reserve University in Cleveland, Sharyl joined the University of Pittsburgh School of Medicine faculty as a tenure track Assistant Professor of Pediatric Neurology. Her work was supported by the National Multiple Sclerosis Society and NIH R01 funding from the National Institute of Neurological Disorders and Stroke (NINDS). Sharyl joined Ultragenyx in 2016 as the Director of Molecular Biology where she leads a research team of scientists and associates who are focusing their efforts on the company’s preclinical neuroscience programs, including an AAV9 gene therapy for CDD. In addition to her role at Ultragenyx, Sharyl is currently serving as a scientific advisory board member for the PCH19 Epilepsy Alliance.

Tim Benke, MD, Ph.D. is the Ponzio Family Chair in Neurology Research and Professor of Pediatrics, Pharmacology, Neurology, and Otolaryngology at University of Colorado School of Medicine.

His lab studies the function of synapses, the primary means of communication between neurons in the brain. Discoveries include mechanisms for synaptic changes that are likely associated with learning and memory. Research is directed at discovering how synapses change with development and following seizures. Our results are specifically directed to help prevent and treat the effects of early-life seizures (ELS), which can include autism, learning impairment and epilepsy.

We focus primarily on the hippocampus in rodents using direct observations of synaptic function with field recordings and whole-cell patch clamp measurements of synaptic events in living brain slices. Western-blot techniques and immunohistochemistry are used to probe protein expression and localization. Pharmacological manipulations are added to determine potential therapies. We use in vivo behavioral techniques to further confirm and advance our translational findings back to the bedside.

Outside of the lab, clinical activities and projects in the Neurosciences Institute at Children’s Hospital Colorado run intellectually in parallel. We are interested in determining the molecular basis and natural history of autism, epilepsy and intellectual disability. We focus on Rett syndrome (allMECP2 related disorders), CDKL5 deficiency syndrome, GRIN disorders, infantile spasms and Down syndrome. All of these disorders can be associated with autism, epilepsy and intellectual disability. Additional efforts focus on the diagnosis of neurogenetic disorders in patients with autism, epilepsy and intellectual disability.