GCase85

GCase85 is a rationally engineered, more stable variant of the human enzyme glucocerebrosidase (GCase), designed to address deficiencies caused by mutations in the GBA1 gene. These mutations are implicated in Gaucher disease and a subset of Parkinson’s disease. Compared to wildtype GCase, GCase85 demonstrates significantly higher enzymatic activity and enhanced stability both in vitro and in vivo, resulting in greater substrate clearance and longer persistence within tissues. In preclinical models, it reduces pathological α-Synuclein accumulation—a hallmark of Parkinson’s disease—more effectively than wildtype enzyme. The primary therapeutic approach involves delivering the gene encoding GCase85 via adeno-associated virus (AAV) vectors as part of investigational gene therapies such as FLT201 for Gaucher disease (liver-targeted) and SPR301 for Parkinson’s disease with GBA1 mutations (brain-targeted). Spur Therapeutics is developing these therapies with the aim to provide durable, potentially one-time treatments that could eliminate or reduce reliance on current chronic therapies[1][2][3][4][5][6][8][9][10].