Patient-Derived Phenotypic High-Throughput Assay to Identify Small Molecules Restoring Lysosomal Function in Tay-Sachs Disease.

ABSTRACT: Tay-Sachs disease is an inherited lysosomal storage disease resulting from mutations in the lysosomal enzyme, β-hexosaminidase A, and leads to excessive accumulation of GM2 ganglioside. Tay-Sachs patients with the infantile form do not live beyond 2-4 years of age due to rapid, progressive neurodegeneration. Enzyme replacement therapy is not a therapeutic option due to its inability to cross the blood-brain barrier. As an alternative, small molecules identified from high-throughput screening could provide leads suitable for chemical optimization to target the central nervous system. We developed a new high-throughput phenotypic assay utilizing infantile Tay-Sachs patient cells based on disrupted lysosomal calcium signaling as a monitor of diseased phenotype. The assay was validated in a pi

SUBMITTER: Colussi DJ 

PROVIDER: S-EPMC7335428 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature