テラワキ　セイゴウ   Seigo Terawaki   寺脇　正剛    所属   川崎医科大学  医学部 基礎医学　分子遺伝医学    職種   特任講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Triclabendazole suppresses cellular levels of glycosaminoglycan-A potential therapeutic agent for mucopolysaccharidoses and related diseases.
掲載誌名	正式名：iScience 略　 称：iScience ISSNコード：25890042/25890042
掲載区分	国外
巻・号・頁	28(8),pp.113118
国際共著	国際共著
著者・共著者	Seigo Terawaki, Filipp Vasilev, Viktoriia Sofronova, Misa Tanaka, Yoshiko Mori, Rina Iwata, Takahito Moriwaki, Toshiharu Fujita, Nadezhda Maksimova, Takanobu Otomo
担当区分	筆頭著者
発行年月	2025/08
概要	Mucopolysaccharidosis-plus syndrome (MPSPS) is an autosomal recessive inherited disorder of mucopolysaccharide metabolism with a severe clinical course. The causative gene VPS33A regulates membrane trafficking, including autophagy and endocytosis. However, how the patient-specific mutation impacts VPS33A function is unknown. We have contrived an experimental method utilizing flow cytometry to evaluate protein levels required for certain cellular functions, named DEFAC, and concluded that the mutant VPS33A has a comparable function in autophagy to the wild-type at the molecular level. There is no specific treatment for MPSPS that is not due to lysosomal enzyme deficiencies or known VPS33A functions. We screened the FDA-approved drug library and identified triclabendazole as a potential curative for MPSPS. Triclabendazole reduced mucopolysaccharide in MPSPS and Mucopolysaccharidosis model cells and represented therapeutic effects on MPSPS model mice. These results suggest that triclabendazole is a widely applicable therapeutic not only to MPSPS but also to related diseases with mucopolysaccharide accumulation.
DOI	10.1016/j.isci.2025.113118
PMID	40822349