Research Award

Puneet Opal, MD, PhD

Northwestern University Medical School, Chicago, IL
Cellular mechanisms underlying SCA1 pathogenesis

Spinocerebellar ataxia type 1 (SCA1) is an inherited disease that causes progressive instability of gait or ataxia. Unfortunately, there is no treatment for this relentless disease and those afflicted succumb to complications of cerebellar and brainstem dysfunction. This disease is
caused by an expansion of glutamines (glutamine is an amino acid) in the disease causing protein, ataxin-1. Recent evidence suggests that mutant ataxin-1 causes alterations in gene expression. In searching for genes directly down-regulated by mutant ataxin-1, we have identified the angiogenic/trophic factor VEGF (Vascular Endothelial Growth Factor) that is also significantly decreased in the brains of the SCA1 mouse model. This proposal tests the hypothesis that low levels of VEGF in SCA1 contribute to the cerebellar dysfunction and degeneration characteristic of this disease. Our long term goal is to use these insights to elucidate mechanisms that will help reverse pathology of this otherwise incurable disease.