[Molecularly-Targeted Therapy of Spinocerebellar Ataxia Type 1 by HMGB1]

Spinocerebellar ataxia type 1 (SCA1) is an untreatable neurodegenerative disease. We reported a decrease in HMGB1 levels in the nucleus of cerebellar neurons in mouse SCA 1. The decrease in this DNA architectural protein leads to the impairment of DNA repair and transcription, the two essential nuclear functions, and eventually causes neurodegeneration. We have designed a gene therapy using AAV-HMGB1 and tested it using the mouse model. Based on the results of these proof of concept (POC) studies, we are now preparing GMP-level AAV vector and designing human clinical trials.