Menkes disease: Oral administration of glyoxal-bis(n(4)-methylthiosemicarbazonato)-copper(ii) rescues the macular mouse

Mitsutoshi Munakata, Hiroko Kodama, Norihiko Tani, Kazuhiko Kimura, Hideyo Takahashi, Kazuo Maruyama, Yoshimasa Sakamoto, Shigeo Kure

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


BACKGROUND: Menkes disease is a copper metabolism disorder caused by mutations in ATP7A, a copper-transporting P-type ATPase. In this study, oral copper supplementation via glyoxal-bis(N(4)-methylthiosemicarbazonato)-copper(II) (CuGTSM), a lipophilic copper complex, was investigated in male hemizygous macular (MoMl/y ) mice, a mouse model of Menkes disease. METHODS: CuGTSM was administered by oral gavage on postnatal days 5, 8, 11, 17, 23, and 32. The copper levels in the organs and serum, copper-dependent enzyme activities in the brain, and ceruloplasmin (Cp) activity in the serum were measured at 15 days and 3 and 8 months of age. Histological analysis of the intestines and the rotarod test were also performed. RESULTS: CuGTSM treatment extended the lifespan of MoMl/y mice and partly restored the copper concentrations and cytochrome oxidase and DBH activities in the brain; however, the rotarod test showed impaired motor performance. The treatment also increased copper concentrations and Cp activity in the serum. In suckling MoMl/y mice, CuGTSM treatment transiently induced diarrhea accompanied by copper accumulation and altered villus morphology in the ileum. CONCLUSION: Oral administration of CuGTSM extended the lifespan of MoMl/y mice. Oral administration is attractive, but pharmaceutical studies are needed to reduce the adverse enteral effects.

Original languageEnglish
Pages (from-to)770-777
Number of pages8
JournalPediatric Research
Issue number5
Publication statusPublished - 2018 Nov 1

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health


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