AT3375

**AT3375** is a next-generation, orally administered small molecule pharmacological chaperone developed by Amicus Therapeutics that specifically targets and stabilizes the glucocerebrosidase (GCase) enzyme, which is deficient in Gaucher disease due to GBA1 mutations and implicated in Parkinson's disease risk. By binding to GCase, it enhances proper folding, trafficking to lysosomes, and enzymatic activity in tissues including the brain, demonstrating improved brain penetration, potency, and rapid clearance compared to first-generation chaperones like AT2101 (isofagomine). Preclinical studies show it reduces alpha-synuclein accumulation, brain inflammation, and motor deficits in alpha-synuclein overexpressing models of Parkinson's, increases GCase activity in Gaucher patient-derived cells and mouse models (liver, spleen, lung, brain), and augments enzyme replacement therapy (ERT) by stabilizing recombinant GCase, minimizing denaturation, and boosting activity in plasma and tissues.[1][3]