Grantee: Paul T. Kotzbauer, MD, PhD
Assistant Professor at Department of Neurology, Washington University School of Medicine
Location: St. Louis, Missouri, United States
Amount: $350,000
Dates: 2017-2019

Dr. Kotzbauer obtained his MD and PhD degrees from Washington University School of Medicine. He completed his neuroscience graduate research in the laboratory of Dr. Jeffrey Milbrandt. He completed clinical training in Neurology and subspecialty training in Movement Disorders at the University of Pennsylvania.  He also completed further research training in neurodegenerative disorders as a Howard Hughes Medical Institute Physician Postdoctoral Fellow in the laboratory of Dr. Virginia Lee.

He is currently an Associate Professor of Neurology at Washington University in St. Louis, where his work is devoted to both research and patient care. His research focuses on disease mechanisms and the development of improved diagnostic and therapeutic approaches in Parkinson disease (PD) as well as a group of hereditary neurological disorders known as Neurodegeneration with Brain Iron Accumulation (NBIA). His NBIA research focuses on improved understanding of disease mechanisms and the development of therapeutics for disorders caused by mutations in the PANK2 and PLA2G6 genes. This includes approaches to improve the function of mutant PANK2 and PLA2G6 enzymes as well as approaches to compensate for impaired enzyme function.

Dr. Kotzbauer is working to develop treatments for impaired PLA2G6 enzyme function, the underlying cause of Infantile Neuroaxonal Dystrophy (INAD). The PLA2G6 gene encodes an enzyme that catalyzes the production of free fatty acids from lipid molecules called phospholipids and lysophospholipids. Gene mutations that cause INAD interfere with the ability of the PLA2G6 enzyme to function properly. Dr. Kotzbauer is currently developing approaches to screen chemical compounds for their ability to either improve the function of the PLA2G6 enzyme or to stimulate other enzymes to compensate for impaired PLA2G6 function. The goal of the project is to develop efficient and sensitive screening approaches and then to perform initial screens to identify compounds with the desired properties. The initial screening effort could identify molecules that are suitable for further optimization and testing as therapeutic agents. The project will also provide important information about the best strategies for further screening efforts to develop treatments for INAD. In addition, the development of new viral vectors that improve the delivery of genes to the brain strongly support the investigation of gene therapy as a new therapeutic approach.