Eleonor Cox
Research Mentor(s): Sharan Srinivasan
Mentor Department: Neurology
Authors: Eleonor Cox, Michael Bonomo , Sharan Srinivasan
Session: Session 3 (11:00am – 11:50am)
Presentation Type: Poster 114
Abstract
Spinocerebellar ataxias (SCA) are a group of autosomal dominant genetic disorders caused by CAG repeat expansions in the genome. Onset and severity of the disease can vary based on the length of these repeats and SCA type, however in most cases, patients show symptoms around 30-40 years of age. Symptoms include abnormal walking patterns, trouble with vision, eye movement, speech, and swallowing. While there are no established cures for any SCA, several favorable targets have emerged. Among these is the mitochondrial regulator, NRF2. Activators of Nrf2, such as DMF (Dimethyl fumarate), have been proven effective in treating other degenerative neurological disorders such as multiple sclerosis (MS) and Friedreich’s Ataxia. Efficacy in the latter prompts consideration of DMF use in treating SCAs. Here, we sought to determine the ability of DMF to rescue behavioral and degenerative phenotypes in a mouse model of SCA1. Over the course of 16 weeks, DMF was administered orally via drinking water to SCA1 mice, at a dose of 100mg/kg. These mice were then assessed using multiple behavioral tests such as the Barnes Maze, open field, balance beam, and rotarod to measure their cognitive and motor abilities. Following this, mice were sacrificed and cerebellar tissue was obtained through perfusion and analyzed using immunofluorescence. Our behavioral results show that DMF can rescue motor but not cognitive symptoms in SCA1 mice. Additionally, early data demonstrates potential delay in cerebellar neuronal degeneration. Future research will investigate the detailed mechanism behind DMF effects in SCAs, potential toxicity risks, and dose dependence, with a goal of potentially using DMF in human SCA studies.
