Taurine supplementation for prevention of stroke-like episodes in MELAS: a multicentre, open-label, 52-week phase III trial.

Abstract

OBJECTIVE:

The aim of this study was to evaluate the efficacy and safety of high-dose taurine supplementation for prevention of stroke-like episodes of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes), a rare genetic disorder caused by point mutations in the mitochondrial DNA that lead to a taurine modification defect at the first anticodon nucleotide of mitochondrial tRNALeu(UUR), resulting in failure to decode codons accurately.

METHODS:

After the nationwide survey of MELAS, we conducted a multicentre, open-label, phase III trial in which 10 patients with recurrent stroke-like episodes received high-dose taurine (9 g or 12 g 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 tRNALeu(UUR) was measured before and after the trial.

RESULTS:

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, that is, the number of patients achieving a 50% or greater reduction in frequency of stroke-like episodes, was 80% (95% CI 44.4% to 97.5%). Taurine reduced the annual relapse rate of stroke-like episodes from 2.22 to 0.72 (P=0.001). Five patients showed a significant increase in the taurine modification of mitochondrial tRNALeu(UUR) from peripheral blood leukocytes (P<0.05). No severe adverse events were associated with taurine.

CONCLUSIONS:

The current study demonstrates that oral taurine supplementation can effectively reduce the recurrence of stroke-like episodes and increase taurine modification in mitochondrial tRNALeu(UUR) in MELAS.

TRIAL REGISTRATION NUMBER:

UMIN000011908.

• Authors: Yutaka Ohsawa, Hiroki Hagiwara, Shin-Ichiro Nishimatsu, Akihiro Hirakawa, Naomi Kamimura, Hideaki Ohtsubo, Yuta Fukai, Tatsufumi Murakami, Yasutoshi Koga, Yu-Ichi Goto, Shigeo Ohta, Yoshihide Sunada, KN01 Study Group
• Journal: Journal of neurology, neurosurgery, and psychiatry (J Neurol Neurosurg Psychiatry) Vol. 90 Issue 5 Pg. 529-536 (05 2019) ISSN: 1468-330X [Electronic] England
• PMID: 29666206 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Chemical References

• Taurine

Topics

• Administration, Oral
• Adolescent
• Adult
• Dietary Supplements
• Female
• Humans
• MELAS Syndrome (complications)
• Male
• Middle Aged
• Stroke (etiology, prevention & control)
• Taurine (therapeutic use)
• Treatment Outcome
• Young Adult