Combined treatment with oral metronidazole and N-acetylcysteine is effective in ethylmalonic encephalopathy.

TitleCombined treatment with oral metronidazole and N-acetylcysteine is effective in ethylmalonic encephalopathy.
Publication TypeJournal Article
Year of Publication2010
AuthorsViscomi, C, Burlina, AB, Dweikat, I, Savoiardo, M, Lamperti, C, Hildebrandt, T, Tiranti, V, Zeviani, M
JournalNat Med
Volume16
Issue8
Pagination869-71
Date Published2010 Aug
ISSN1546-170X
KeywordsAcetylcysteine, Administration, Oral, Animals, Anti-Infective Agents, Brain Diseases, Metabolic, Inborn, Child, Preschool, Dioxygenases, Drug Combinations, Drug Evaluation, Preclinical, Female, Humans, Infant, Male, Malonates, Metronidazole, Mice, Mice, Knockout, Mitochondrial Proteins, Treatment Outcome
Abstract

Ethylmalonic encephalopathy is caused by mutations in ETHE1, a mitochondrial matrix sulfur dioxygenase, leading to failure to detoxify sulfide, a product of intestinal anaerobes and, in trace amounts, tissues. Metronidazole, a bactericide, or N-acetylcysteine, a precursor of sulfide-buffering glutathione, substantially prolonged the lifespan of Ethe1-deficient mice, with the combined treatment being additive. The same dual treatment caused marked clinical improvement in five affected children, with hardly any adverse or side effects.

DOI10.1038/nm.2188
Alternate JournalNat. Med.
Citation Key10.1038/nm.2188
PubMed ID20657580
Grant ListGGP07019 / / Telethon / Italy
GTF07004 / / Telethon / Italy