PILLAR 1: Learn more about Dr. James Wilson's research
As part of our ongoing effort to highlight how different pieces of research fit into FAST’s 4 Pillars in the Roadmap to a Cure 2.0, we are starting today with “Pillar 1: Fix Mom’s Gene.” This Pillar encompasses all work being done to address deficits due to a lack of a functional maternal UBE3A copy in the brain. First at bat, we are featuring some of the incredible work Dr. James Wilson presented at the 2022 FAST Science Summit.
“The science of gene therapy couldn’t, and hasn’t, been any better than it is now,” Dr. Wilson stated. “We continue to make incredible progress in the technical and clinical development of gene therapy.” There are currently over 2,000 active gene therapy clinical trials (clinicaltrials.gov), promising cutting-edge genetic technologies and a far better understanding of vector delivery methods, making the reality of an Angelman syndrome gene therapy that much closer.
In his work, Dr. Wilson discussed using cross correction, a method where gene-corrected cells travel to the brain and secrete functional UBE3A protein that is then taken up by neighboring, deficient cells. This results in cells that previously had no UBE3A protein due to maternal loss of function now expressing UBE3A. This therapeutic has been tested in both mouse and monkey models via AAV vector. Mouse models showed marked motor and gait rescue after treatment while the monkey studies indicated good vector distribution (i.e., where the therapeutic ended up in the brain) and very strong safety margins when looking at pathology of the spine. They are currently working on drug manufacturing for the animal models, formal dose finding and safety and toxicity studies before proceeding to potential clinical work.
Watch Dr. Wilson's presentation from the 2022 Global Science Summit: