The goal of our laboratory is to elucidate the mechanisms underlying the pathogenesis of spinocerebellar ataxia type 1 (SCA1). SCA1 is an autosomal dominant neurodegenerative disorder that belongs to a family of diseases caused by polyglutamine (polyQ) repeat expansions in the disease causing protein. Our laboratory has found that ATXN1—the protein mutated in SCA1— directly represses expression of vascular endothelial growth factor (VEGF), an angiogenic/trophic factor. Our overarching hypothesis, for which we have considerable evidence, is that decreased levels of VEGF lead to neurodegeneration in SCA1. We seek to develop a novel VEGF mimetic peptide as a therapy for SCA1. In this proposal we will use the SCA1 knock-in mouse model with 154 repeats to test this novel reagent using a battery of tests in preclinical testing. With completion of this study we may have a promising therapeutic for this chronic debilitating and fatal disease for which there is currently no treatment.
|Effective start/end date||3/1/19 → 2/29/20|
- National Ataxia Foundation (Award Letter 2/25/19)