Details

Autor(en) / Beteiligte

• Suzuki, Yoshiyuki
• Ichinomiya, Satoshi
• Kurosawa, Mieko
• Ohkubo, Masato
• Watanabe, Hiroshi
• Iwasaki, Hiroyuki
• Matsuda, Junichiro
• Noguchi, Yoko
• Takimoto, Kazuhiro
• Itoh, Masayuki
• Tabe, Miho
• Iida, Masami
• Kubo, Takatoshi
• Ogawa, Seiichiro
• Nanba, Eiji
• Higaki, Katsumi
• Ohno, Kousaku
• Brady, Roscoe O.

Titel

Chemical chaperone therapy: clinical effect in murine G M1 ‐gangliosidosis

Ist Teil von

• Annals of neurology, 2007-12, Vol.62 (6), p.671-675

Erscheinungsjahr

2007

Quelle

Wiley Online Library All Journals

Beschreibungen/Notizen

• Abstract Certain low‐molecular‐weight substrate analogs act both as in vitro competitive inhibitors of lysosomal hydrolases and as intracellular enhancers (chemical chaperones) by stabilization of mutant proteins. In this study, we performed oral administration of a chaperone compound N ‐octyl‐4‐epi‐β‐valienamine to G M1 ‐gangliosidosis model mice expressing R201C mutant human β‐galactosidase. A newly developed neurological scoring system was used for clinical assessment. N ‐Octyl‐4‐epi‐β‐valienamine was delivered rapidly to the brain, increased β‐galactosidase activity, decreased ganglioside G M1 , and prevented neurological deterioration within a few months. No adverse effect was observed during this experiment. N ‐Octyl‐4‐epi‐β‐valienamine will be useful for chemical chaperone therapy of human G M1 ‐gangliosidosis. Ann Neurol 2007