MELAS and l-arginine therapy

Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) is a maternally inherited multisystem mitochondrial disorder characterized by stroke-like episodes before 20 years of age [ ]. Mitochondrial angiopathy, with degenerative changes in small arteries and arterioles, has been reported in many MELAS patients [ ]; these blood vessels have been designated as strongly succinate dehydrogenase-reactive vessels (SSVs) [ ]. However, the primary cause for stroke-like episodes in young MELAS patients—whether mitochondrial cytopathy, angiopathy, or both—remains controversial. Many therapeutic trials have been undertaken to cure mitochondrial disorders, but not for the acute stroke phase of MELAS. Based on a hypothesis that stroke-like episodes in MELAS are caused by segmental impairment of vasodilation in intracerebral arteries, l-arginine has been used for therapeutic trials in MELAS patients during the acute phase of stroke. We found that l-arginine therapy quickly decreased severity of stroke-like symptoms in MELAS, enhanced dynamics of microcirculation, and also reduced tissue injury from ischemia [ ]. l-arginine is a potent vasodilator via endothelial function through nitric oxide (NO) production [ ]. Cardioprotective effects of l-arginine and NO are associated with endothelial cell preservation [ ], decreased neutrophil activation [ ], improved coronary blood flow, and reduced free radical-mediated injury [ ]. Although the molecular mechanism of l-arginine therapy in MELAS is not known, it is a potential new therapy for use at the acute phase of stroke-like episodes in MELAS.