GT-02329

GT-02329 is an orally bioavailable, brain-penetrant, small molecule **structurally targeted allosteric regulator** (STAR) developed by Gain Therapeutics for diseases associated with mutations in the GBA1 gene, including **Gaucher disease** (types II and III, neuronopathic forms) and **GBA1-associated Parkinson’s disease**. GT-02329 enhances the activity of the lysosomal enzyme **β-glucocerebrosidase** (GCase), stabilizing misfolded GCase proteins, increasing their lysosomal transport, and restoring enzymatic function. This process leads to a reduction in toxic lipid substrates (glucosylceramide and glucosylsphingosine), reduction of neuroinflammation, and decreased pathological α-synuclein species in relevant neuron types. Mechanistically, GT-02329 acts by binding a novel allosteric site on GCase, distinct from the active site, to both stabilize and enhance function of pathogenic GCase variants, and has shown the ability to improve neuromuscular function and reduce behavioral deficits in preclinical models of disease. The molecule is a **first-in-class disease-modifying therapy** candidate for synucleinopathies and lysosomal storage disorders[1][2][3][4][7][9][11][12][13].