Neurodegenerative diseases represent an ever-increasing societal and economic burden with World Health Organization estimates indicating that they will replace cancer as the 2nd leading cause of death by 2040.
Spinocerebellar ataxia type 2 (SCA2) is a part of a family of progressive, often fatal neurodegenerative diseases with no known treatments or cures. Dominantly-acting mutations lead to expansion of a polyQ domain in the ataxin-2 (ATXN2) protein. Assembly of RNA-binding protein Staufen-1 (STAU1) with mutant ATXN2 in stable inclusions is causative, resulting in aberrant RNA processing in SCA2 and other neuronal diseases such as ALS. The proposed technology identifies STAU1 as an interventional target with STAU1 antisense therapeutic alleviating the severity of the disease in a mouse model of SCA2.