Chemical chaperone therapy for GM1-gangliosidosis
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- Suzuki, Y. Cell. Mol. Life Sci. (2008) 65: 351. doi:10.1007/s00018-008-7470-2
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We have proposed a chemical chaperone therapy for lysosomal diseases, based on a paradoxical phenomenon that an exogenous competitive inhibitor of low molecular weight stabilizes the target mutant molecule and restores its catalytic activity as a molecular chaperone intracellularly. After Fabry disease experiments, we investigated a new synthetic chaperone compound N-octyl-4-epi-β-valienamine (NOEV) in a GM1-gangliosidosis model mice. Orally administered NOEV entered the brain through the blood-brain barrier, enhanced β-galactosidase activity, reduced the substrate storage, and clinically improved neurological deterioration. We hope that chemical chaperone therapy will prove useful for some patients with GM1-gangliosidosis and potentially other lysosomal storage diseases with central nervous system involvement.