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

Autor:	Ohsawa Y; Department of Neurology, Kawasaki Medical School, Kurashiki, Japan., Hagiwara H; Department of Medical Science, Teikyo University of Science, Adachi-ku, Japan., Nishimatsu SI; Department of Natural Science, Kawasaki Medical School, Kurashiki, Japan., Hirakawa A; Center for Advanced Medicine and Clinical Research, Statistical Analysis Section, Nagoya University Hospital, Nagoya, Japan.; Graduate School of Medicine, Department of Biostatistics and Bioinformatics, The University of Tokyo, Tokyo, Japan., Kamimura N; Department of Biochemistry and Cell Biology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan., Ohtsubo H; Department of Neurology, Kawasaki Medical School, Kurashiki, Japan., Fukai Y; Department of Neurology, Kawasaki Medical School, Kurashiki, Japan., Murakami T; Department of Neurology, Kawasaki Medical School, Kurashiki, Japan., Koga Y; Department of Pediatrics and Child Health, Kurume University Graduate School of Medicine, Kurume, Japan., Goto YI; The Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan., Ohta S; Department of Biochemistry and Cell Biology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.; Department of Neurology, Juntendo University Graduate School of Medicine, Bunkyo-ku, Japan., Sunada Y; Department of Neurology, Kawasaki Medical School, Kurashiki, Japan.
Jazyk:	angličtina
Zdroj:	Journal of neurology, neurosurgery, and psychiatry [J Neurol Neurosurg Psychiatry] 2019 May; Vol. 90 (5), pp. 529-536. Date of Electronic Publication: 2018 Apr 17.
DOI:	10.1136/jnnp-2018-317964
Abstrakt:	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 tRNA Leu(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 tRNA Leu(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 tRNA Leu(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 tRNA Leu(UUR) in MELAS. Trial Registration Number: UMIN000011908. Competing Interests: Competing interests: YS reports the following research grants: Intramural Neurological and Psychiatric Disorders from the National Center of Neurology and Psychiatry (26-8), Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (C-24591281, C-26461285) and by research project grants from Kawasaki Medical School (23-T1, 26-T1). (© 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.)
Databáze:	MEDLINE
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