Therapeutic chaperone effect of N-Octyl 4-Epi-β-valienamine on murine GM1-gangliosidosis

Therapeutic chaperone effect of a valienamine derivative N-octyl 4-epi-β-valienamine (NOEV) was studied in GM1-gangliosidosis model mice. Phamacokinetic analysis revealed rapid intestinal absorption and renal excretion after oral administration. Intracellular accumulation was not observed after continuous treatment. NOEV was delivered to the central nervous system through the blood–brain barrier to induce high expression of the apparently deficient β-galactosidase activity. NOEV treatment starting at the early stage of disease resulted in remarkable arrest of neurological progression within a few months. Survival time was significantly prolonged. This result suggests that NOEV chaperone therapy will be clinically effective for prevention of neuronal damage if started early in life hopefully also in human patients with GM1-gangliosidosis.

► Chaperone effect of NOEV is reported on murine GM1-gangliosidosis.
► Pharmacokinetic parameters were determined.
► NOEV was absorbed in the intestine and excreted in the urine.
► Brain pathology was remarkably improved after long-term chaperone treatment.
► Survival time was significantly prolonged by NOEV.