@article {Ohsawa529, author = {Yutaka Ohsawa and Hiroki Hagiwara and Shin-ichiro Nishimatsu and Akihiro Hirakawa and Naomi Kamimura and Hideaki Ohtsubo and Yuta Fukai and Tatsufumi Murakami and Yasutoshi Koga and Yu-ichi Goto and Shigeo Ohta and Yoshihide Sunada}, editor = {, and , and Onoue, H and Kaida, K and Sato, K and Uchiyama, T and Ueda, A and Mutoh, T and Nakamura, M and Nishida, K and Funakawa, I and Ogawa, A and Nakata, R and Shiraishi, H and Tsujino, A and Takahashi, T and Matsumoto, M}, title = {Taurine supplementation for prevention of stroke-like episodes in MELAS: a multicentre, open-label, 52-week phase III trial}, volume = {90}, number = {5}, pages = {529--536}, year = {2019}, doi = {10.1136/jnnp-2018-317964}, publisher = {BMJ Publishing Group Ltd}, 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.}, issn = {0022-3050}, URL = {https://jnnp.bmj.com/content/90/5/529}, eprint = {https://jnnp.bmj.com/content/90/5/529.full.pdf}, journal = {Journal of Neurology, Neurosurgery \& Psychiatry} }