{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T13:36:37Z","timestamp":1779197797347,"version":"3.51.4"},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2005,12,1]],"date-time":"2005-12-01T00:00:00Z","timestamp":1133395200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2005,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Menkes disease (MD) is a neurodegenerative disorder characterized by a copper deficiency in the brain. It is caused by the defective intestinal absorption of copper resulting from a deficiency of a copper\u2010transporting ATPase, ATP7A. This gives rise to an accumulation of copper in the intestine. The copper deficiency in the brain of MD patients cannot be improved by copper injections, because the administered copper accumulates at the blood\u2013brain barrier and is not transported across to the neurons. To resolve this problem, we investigated the effect of a combination therapy of copper and sodium diethyldithiocarbamate (DEDTC), a lypophilic chelator, in an animal model of MD, the macular mouse. Four\u2010week\u2010old macular mice treated with 50 \u03bcg of CuCl<jats:sub>2<\/jats:sub> on the 7th day after birth were used. Experimental mice were given a subcutaneous injection of CuCl<jats:sub>2<\/jats:sub> (4 \u03bcg) and an intraperitoneal injection of DEDTC (0.2 mg\/g body weight) twice a week for 4 weeks and then sacrificed. Copper concentrations and cytochrome\u2010<jats:italic>c<\/jats:italic> oxidase activity in the brains of treated mice were higher than those of control macular mice, which received only copper or saline. The ratios of brain noradrenaline to dopamine and of adrenaline to dopamine were also increased by the treatment, suggesting that the activity of dopamine \u03b2\u2010hydroxylase, a copper\u2010dependent enzyme, was improved by the treatment. Liver and renal function tests showed no abnormalities in the treated mice, although copper concentrations in the kidneys of treated mice were higher than those of control macular mice. These results suggest that DEDTC facilitates the passage of copper across the blood\u2013brain barrier and that the combination therapy of copper and DEDTC may be an effective treatment for the neurological disturbances suffered by patients with MD.<\/jats:p>","DOI":"10.1007\/s10545-005-0150-6","type":"journal-article","created":{"date-parts":[[2006,1,25]],"date-time":"2006-01-25T09:35:29Z","timestamp":1138181729000},"page":"971-978","source":"Crossref","is-referenced-by-count":32,"title":["Effect of copper and diethyldithiocarbamate combination therapy on the macular mouse, an animal model of Menkes disease"],"prefix":"10.1002","volume":"28","author":[{"given":"H.","family":"Kodama","sequence":"first","affiliation":[{"name":"Department of Pediatrics Teikyo University School of Medicine 11\u20101, Kaga\u20102 Itabashi\u2010ku Tokyo 176\u20108605 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