New treatment for inborn error of metabolism

Combined treatment with two drugs, metronidazole and N-acetylcysteine, is effective in treating children with ethylmalonic encephalopathy ― a birth defect of the metabolism that affects the gastrointestinal, circulatory, and nervous systems. The article in this week's Nature Medicine suggests that this therapy may be useful in the treatment of children suffering from the genetic disorder.

Ethylmalonic encephalopathy is caused by mutations in a mitochondrial protein important for metabolizing sulfide. As sulfide is largely a product of intestinal microbes, Massimo Zeviani and colleagues tested the effect of an antibiotic ― metronidazole ― together with N-acetylcysteine ― a precursor of the sulfide-buffering molecule ― in mice and in patients with this disease.

The treatment substantially prolonged the lifespan of mice carrying disease-causing mutations and resulted in marked clinical improvement in five affected children, with no adverse effects. A larger clinical trial will now be necessary to confirm these encouraging results.