Gene Therapy in Angelman Syndrome
Summary of Dr. Gray study
Dr. Steven Gray is applying his years of experience using gene therapy as a treatment for Giant Axonal Neuropathy (GAN), Rett syndrome, and several other neurological disorders to Angelman syndrome. Dr. Gray has been a pioneer in the field of developing AAV (adeno-associated virus) vectors to inject into the spinal fluid, a strategy that is being used to treat several neurogenetic disorders. Dr. Gray also has specific experience in translating gene therapy treatments from lab testing into human testing. He led the development of the first delivery of a viral gene therapy vector injected into the spinal fluid of humans. Thus, he has a toolkit of knowledge to navigate any unknown challenges that may arise in applying gene therapy to Angelman syndrome.
Dr. Gray’s overall strategy is first envisioning how a human treatment would be administered and dosed, and then scale that back to lab studies to directly model how they envision the treatment in humans. Dr. Gray is taking an aggressive approach: deliver AAV vectors in high doses in AS-mice lab studies to determine the “best- and worst-case scenario” upper bar for treatment. If that proves safe, then it provides latitude to move towards a human treatment much more quickly. If it is not safe, then the approach can be scaled back and/or redesigned. The research team anticipates the possibility of UBE3A gene therapy complications due to experience with some other disorders such as Rett syndrome, so the initial priority is to determine how safe or unsafe this gene therapy approach may be. This will provide a guide for gene therapy in Angelman syndrome for future studies and treatments with the ultimate goal of accelerating a cure for Angelman syndrome.