title: Therapeutic chaperone effect of N-octyl 4-epi-β-valienamine on murine G(M1)-gangliosidosis.
abstract: Therapeutic chaperone effect of a valienamine derivative N-octyl 4-epi-β-valienamine (NOEV) was studied in G(M1)-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 G(M1)-gangliosidosis.
authors.affiliation: Graduate School, International University of Health and Welfare, Otawara, Japan. suzukiy@iuhw.ac.jp
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ichinomiya
authors.forename: Mieko
authors.initials: M
authors.lastname: Kurosawa
authors.forename: Junichiro
authors.initials: J
authors.lastname: Matsuda
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Ogawa
authors.forename: Masami
authors.initials: M
authors.lastname: Iida
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Kubo
authors.forename: Miho
authors.initials: M
authors.lastname: Tabe
authors.forename: Masayuki
authors.initials: M
authors.lastname: Itoh
authors.forename: Katsumi
authors.initials: K
authors.lastname: Higaki
authors.forename: Eiji
authors.initials: E
authors.lastname: Nanba
authors.forename: Kousaku
authors.initials: K
authors.lastname: Ohno
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D002490:Central Nervous System / Q000201:enzymology / Q000473:pathology; D004195:Disease Models, Animal; D016537:Gangliosidosis, GM1 / Q000201:enzymology / Q000473:pathology / Q000628:therapy*; D005786:Gene Expression Regulation / Q000187:drug effects; D006595:Hexosamines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018832:Molecular Chaperones / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016482:Urinalysis; D001616:beta-Galactosidase / Q000235:genetics*; D001617:beta-Glucosidase / Q000235:genetics*
chemical_list: D006595:Hexosamines; D018832:Molecular Chaperones; C116532:N-octyl-beta-valienamine; D001617:beta-Glucosidase; D001616:beta-Galactosidase