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Therapeutic regimen of L-arginine for MELAS: 9-year, prospective, multicenter, clinical research.

ABSTRACT: OBJECTIVE:To examine the efficacy and safety of the therapeutic regimen using oral and intravenous L-arginine for pediatric and adult patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). METHODS:In the presence and absence of an ictus of stroke-like episodes within 6 h prior to efficacy assessment, we correspondingly conducted the systematic administration of oral and intravenous L-arginine to 15 and 10 patients with MELAS in two, 2-year, prospective, multicenter clinical trials at 10 medical institutions in Japan. Subsequently, patients were followed up for 7 years. The primary endpoint in the clinical trial of oral L-arginine was the MELAS scale, while that for intravenous L-arginine was the improvement rates of headache and nausea/vomiting at 2 h after completion of the initial intravenous administration. The relationships between the ictuses of stroke-like episodes and plasma arginine concentrations were examined. RESULTS:Oral L-arginine extended the interictal phase (p?=?0.0625) and decreased the incidence and severity of ictuses. Intravenous L-arginine improved the rates of four major symptoms-headache, nausea/vomiting, impaired consciousness, and visual disturbance. The maximal plasma arginine concentration was 167 ?mol/L when an ictus developed. Neither death nor bedriddenness occurred during the 2-year clinical trials, and the latter did not develop during the 7-year follow-up despite the progressively neurodegenerative and eventually life-threatening nature of MELAS. No treatment-related adverse events occurred, and the formulations of L-arginine were well tolerated. CONCLUSIONS:The systematic administration of oral and intravenous L-arginine may be therapeutically beneficial and clinically useful for patients with MELAS.

SUBMITTER: Koga Y

PROVIDER: S-EPMC6244654 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Therapeutic regimen of L-arginine for MELAS: 9-year, prospective, multicenter, clinical research.

Koga Yasutoshi Y Povalko Nataliya N Inoue Eisuke E Nakamura Hidefumi H Ishii Akiko A Suzuki Yasuhiro Y Yoneda Makoto M Kanda Fumio F Kubota Masaya M Okada Hisashi H Fujii Katsunori K

Journal of neurology 20180929 12

<h4>Objective</h4>To examine the efficacy and safety of the therapeutic regimen using oral and intravenous L-arginine for pediatric and adult patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS).<h4>Methods</h4>In the presence and absence of an ictus of stroke-like episodes within 6 h prior to efficacy assessment, we correspondingly conducted the systematic administration of oral and intravenous L-arginine to 15 and 10 patients with MELAS in two ...[more]

PMID: 30269300

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Dataset Information

Therapeutic regimen of L-arginine for MELAS: 9-year, prospective, multicenter, clinical research.

Publications

Therapeutic regimen of L-arginine for MELAS: 9-year, prospective, multicenter, clinical research.

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