The study on a new therapy of Menkes disease

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Menkes disease is a neurodegenerative disorder characterized by a copper deficiency in various organs including the brain and liver. On the contrary, copper accumulated in the kidney and intestine. These abnormalities of copper distribution are caused by a reduced membrane-transport of copper. We examined effects of a combination therapy of a subcutaneous copper administration and an oral administration of a chelating agent (N,N-diethyl carbamirate) on copper metabolism in the macular mouse, an animal model of Menkes disease. 【Materials and Methods】 Four weeks old macular mice and control mice were used. Copper (20μg/time) and diethyl carbamirate (0.05 mg/g body weight/time) were given twice a week for 4 weeks. After that, the mice were sacrificed, and the brain, liver, kidney and intestine were obtained. Copper concentrations in those tissues were analyzed with an atomic absorption spectrophotometer. The activity of cytochrome C oxidase in those tissues was also examined. 【Results and Discussion】 The copper concentration were improved in the brain and liver of macular mice that were treated with a combination of copper and a chelating agent. The copper concentrations were not changed in the kidney and intestine of the treated macular mice. However, the activities of cytochrome C oxidase were decreased in the brain and kidney of macular mice that were treated with the combination therapy. These results suggest that copper distribution was improved with the combination therapy, however, the copper enzyme activities were not improved by the therapy.