Ataluren for Nonsense Mutation Methylmalonic Acidemia

Methylmalonic acidemia (MMA) is a rare genetic disorder caused by mutations in the gene for mitochondrial enzyme methylmalonyl-CoA mutase (MCM) or in one of the genes for adenosylcobalamin (AdoCbl). Lack of these proteins causes toxic elevations of methylmalonic acid (MMacid) in blood, urine, and other tissues. A specific type of mutation, called a nonsense (premature stop codon) mutation, is the cause of the disease in approximately 5% to 20% of participants with mutations in the MCM gene, and approximately 20% to \>50% of participants with mutations in one of the AdoCbl genes. Ataluren is an orally delivered, investigational drug that acts to overcome the effects of the premature stop codon, potentially enabling the production of functional MCM/AdoCbl. This study is a Phase 2a trial evaluating the safety and activity of ataluren in participants with MMA due to a nonsense mutation. The main purpose of this study is to understand whether ataluren can safely decrease MMacid levels.