Arginine therapy in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes

Abstract

© 2020 Lippincott Williams and Wilkins. All rights reserved. Purpose of reviewWe would like to inform clinicians that the systematic administration of oral and intravenous l-Arginine is therapeutically beneficial and clinically useful for patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), when they maintain plasma arginine concentration at least 168 μmol/l.Recent findingsMELAS is associated with endothelial dysfunction by decreased plasma l-Arginine, nitric oxide (NO), and cyclic guanosine monophosphate. Endothelial dysfunction is also evident using flow-mediated vasodilation measurement by high-resolution Doppler echocardiography in the forearm artery in patients with MELAS. l-Arginine is known to be an important precursor of NO to normalize the endothelial function in MELAS. In our clinical trial followed by 7 years follow-up study, the systematic administration of l-Arginine to patients with MELAS significantly improved the survival curve of patients compared with natural history. Maintaining plasma arginine concentration at least 168 μmol/l may prevent the ictuses through the putative pathophysiologic mechanism and optimal normalization of endothelial dysfunction.SummaryNeither 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. Therapeutic regimen of l-Arginine on MELAS may be beneficial and clinically useful for patient care with MELAS.