Development of BDNF Potentiating Therapeutics for Motor and Cognitive Dysfunction in Angelman Syndrome

What is BDNF? Brain-derived neurotrophic factor (BDNF) is a vital protein essential for regulating the cellular processes that underlie learning and memory in the brain, and this protein has been found to be impacted negatively by the lack of function UBE3A, as seen in Angelman syndrome (AS). The mouse model of AS shows a defect in BDNF receptor signaling, which is thought to play a role in cognition in humans.

Preliminary studies by Dr. John Marshall of Brown University show that the deficits in learning observed in a mouse model of AS may stem from reduced BDNF activity. This project will test a novel class of therapeutics called Syn compounds that have been shown to facilitate learning and restore normal mobility in the AS mice. The Syn compounds will be thoroughly explored in the AS mouse while understanding how analogs of the compound can be advanced toward human application with novel drug delivery approaches. In humans, these compounds are aimed to facilitate learning, improved motor function and overall coordination, all of which are significantly impacted by those living with AS. This study will support numerous Syn compounds to undergo further animal studies to determine which has the best safety profile and the ability to treat the symptoms (learning and walking/gait/coordination) in the AS animal models. The results of this project will be used to inform a potential novel treatment option for humans living with Angelman syndrome.

Dr. Marshall, the recipient of this grant, will be speaking at FAST's Translational Research Symposium on his preliminary data on December 1, 2022. We welcome Dr. Marshall to the AS community.