Gain Therapeutics announces preclinical data on class of allosteric regulators

Gain Therapeutics announced the publication of preclinical data identifying a novel class of small molecule allosteric regulators that demonstrate therapeutic potential for galactosidase beta 1-related lysosomal storage disorders, including GM1 gangliosidosis. The study, “Validation of a highly sensitive HaloTag-based assay to evaluate the potency of a novel class of allosteric beta-Galactosidase correctors,” was published in PLOS ONE. GM1-gangliosidosis is an inherited, progressive disorder characterized by the degeneration of brain and spinal cord cells, leading to muscle weakness, skeletal abnormalities, dystonia, and vision problems. Mutations in the GLB1 gene significantly reduce the activity and function of the lysosomal hydrolase enzyme beta-galactosidase due to protein misfolding. Depending on the age of onset, which can occur during infancy and up into adulthood, life expectancy of patients can be significantly shortened. Additionally, there are no available disease-modifying treatments for GM1 gangliosidosis, with available therapies only focused on reducing symptoms and improving quality of life. To enhance patient outcomes, there is a significant need to bring safe and effective treatments into the clinic that can alter progression of the disorder. In the PLOS ONE study, scientists from Gain used Gain’s proprietary Site-directed Enzyme Enhancement Therapy technology followed by molecular interaction and ligand binding studies to identify and characterize two structurally targeted allosteric regulators of beta-Gal. A biochemical HaloTag cleavage assay was developed by the researchers from the Institute for Research in Biomedicine and utilized to measure lysosomal delivery capabilities of beta-Gal. Results showed that the two compounds stabilized, enhanced and restored the key biological lysosomal transport functions of beta-Gal and reduced the levels of the intracellular toxic substrate, GM1 ganglioside, in GM1 gangliosidosis patient-derived cells.