Taurine therapy for MELAS, a major mitochondrial disease

Abstract

MELAS is a major clinical entity of mitochondrial diseases and is characterized by recurrent stroke–like episodes. Point mutations in the mitochondrial DNA including 3243A>G lead to deficiency of taurine modification at the first anticodon nucleotide, which results in failure to decode codons accurately. We previously showed that addition of taurine to the culture media alleviated mitochondrial function in patient–derived pathogenic cells. In a preliminary study, high–dose oral administration of 12g taurine completely prevented stroke–like episodes in two patients with MELAS for more than 9 years. Based on these preclinical and clinical data, we conducted a multicentre, open–label, phase III trial in which 10 patients with recurrent stroke–like episodes received high–dose taurine (9g or 12g per day) for 52 weeks. The primary endpoint was the complete prevention of stroke–like episodes during the evaluation period. The taurine modification rate of mitochondrial tRNA^Leu(UUR) was measured before and after the trial. The proportion of patients who reached the primary endpoint (100% responder rate) was 60% (95% CI 26.2% to 87.8%). The 50% responder rate was 80% (95% CI 44.4% to 97.5%). Taurine reduced the annual relapse rate of stroke–like episodes from 2.2 to 0.7 (p=0.001). Five patients showed a significant increase in the taurine modification of mitochondrial tRNA^Leu(UUR) from peripheral blood leukocytes (p<0.05). No severe adverse events were associated with taurine. The current study demonstrates that oral taurine supplementation can effectively reduce the recurrence of stroke–like episodes. In February 2019, Japan's Pharmaceutical and Food Safety Bureau granted marketing authorisation to taurine for the prevention of stroke–like episodes in MELAS.