Effect of combination therapy consisting of copper and a chelator for Menkes disiease.

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[Object] Menkes disease is a disorder of copper transport. In patients with Menkes disease, copper accumulates in the intestine, kidney and blood brain barrier (B.B.B.) while the brain remains in a state of copper deficiency. The copper deficiency in the brain cannot be improved by copper injections, because the administered copper accumulates B.B.B. and cannot be transported to neurons. We investigated the effect of combination therapy with administrations of copper and sodium diethyldithiocarbamate (DEDTC), a lypophylic chelator, in the macular mouse.[Methods] Four-week old macular mice that had been treated with 50 ug of CuCl_2 on the 7th day after birth were used. The mice were separated into three groups (group A, chelator + copper ; group B, copper ; group C, saline control). Mice in group A were treated with a subcutaneous injection of CuCl_2 (4 ug) and an intraperitoneal injections of DEDTC (0.2 mg/g) twice a week for 4 weeks and then sacrificed. Mice in group B were treated with only CuCl_22 in the same manner as group A. The brain, kidney and intestine were then dissected, and copper concentration and cytochrome C oxidase (CCO) activity were analyzed.[Results & Conclusions] The copper concentration in the brain of group A was higher than that in group B and C. The CCO activity in the brain was highest in group A. The copper concentrations in the kidneys and intestines of group A were also higher than in group B and C. These results suggest that the chelator enables copper to pass through B.B.B. improving copper deficiency and CCO activity in the brain. However, the combination therapy worsens copper accumulation in the kidney.