Menkes disease is a fatal
neurodegenerative disorder in infants caused by mutations in the gene ATP7A which encodes a
copper (Cu) transporter. Defects in ATP7A lead to accumulated
copper in the small intestine and kidneys and to
copper deficiencies in the brain and the liver. The
copper level in the kidney in postnatal
copper-treated Menkes patients may reach toxic levels. The mouse model, mosaic Atp7a (mo-ms) recapitulates the Menkes phenotype and die about 15.75±1.5 days of age. In the present study we found that prenatal treatment of mosaic murine fetuses throughout gestation days 7, 11, 15 and 18 with a combination of CuCl(2) (50 mg/kg) and
dimethyldithiocarbamate (DMDTC) (280 mg/kg) leads to an increase in survival to about 76±25.3 days, whereas treatment with CuCl(2) alone (50 mg/kg) only leads to survival for about 21 days ±5 days. These
copper-DMDTC treated mutants showed an improved locomotor activity performance and a gain in body mass. In contrast to treatment with CuCl(2) alone, a significant increase in the amount of
copper was observed in the brain after prenatal
copper-DMDTC treatment as well as a decrease in the amount of accumulated
copper in the kidney, both leading towards a normalization of the
copper level. Although
copper-DMDTC prenatal treatment only leads to a small increase in the sub-normal
copper concentration in the liver and to an increase of
copper in the already overloaded small intestine, the combined results suggest that prenatal
copper-DMDTC treatment also should be considered for humans.