NAF Ataxia Research Studies Currently Underway

Punett Opal, MD, PhD

Northwestern University
Understanding Spinocerebellar Ataxia Type 1

Summary: Spinocerebellar ataxia type I (SCAI) 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 a stretch of glutamines (glutamine is an amino acid) in the disease causing protein, ataxin-l. Using SCAI as a model system, our long-term goal is to shed light on two questions pertaining to ataxias: 1.What is the basis for degeneration in cerebellar neurons, the neurons responsible for the co-ordination of movements, and 2.What are the subcellular pathways involved in toxicity? This study addresses both of these issues in SCA l by focusing on an ataxin-l interactor, the Leucine-Rich Acidic Nuclear Protein (LANP).

Based on our preliminary results, we hypothesize that LANP plays a role in SCAI pathogenesis by serving as a mediator of toxicity in SCA l. Indeed, we have some tantalizing preliminary evidence that reducing LANP levels might prove ameliorative in SCA l pathogenesis. This grant probes the neuronal functions of LANP with the final aim of delineating its role in SCA l pathogenesis. We believe that our experiments will help us not only to understand this disease, but also provide clues to treat this otherwise incurable disease.