recombinant adeno-associated virus encoding GTP cyclohydrolase I

rAAV-GCH1 is a gene therapy vector based on recombinant adeno-associated virus (rAAV) engineered to express the GTP cyclohydrolase I (GCH1) gene. GCH1 is the rate-limiting enzyme in the biosynthesis of tetrahydrobiopterin (BH4), an essential cofactor for catecholamine and serotonin synthesis. The primary mechanism of action for rAAV-GCH1 is gene augmentation—restoring or increasing GCH1 expression in target tissues, which in turn increases local BH4 levels, facilitating dopamine and serotonin synthesis[2]. This approach has been investigated primarily in the context of Parkinson’s disease, where it is combined with tyrosine hydroxylase (TH) gene therapy to provide the necessary enzymatic pathway for dopamine synthesis in the striatum, leading to significant and sustained improvement in motor function in preclinical models[2]. rAAV-GCH1 alone can also increase BH4 levels, but the maximal therapeutic effect (especially behavioral recovery) is achieved when combined with TH gene transfer[2].

Other names

recombinant adeno-associated virus-GCH1rAAV vector encoding GCH1