Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is caused by abnormalities in mitochondrial DNA (mtDNA). More than 80% of MELAS cases have a common m.3243A>G mutation in the MTTL1 gene. Onset of MELAS can vary from age 4 to 40 but most of them show symptoms before 20.
MELAS causes recurrent stroke-like episodes in the brain, migraine-type headaches, vomiting and seizures, and can lead to permanent brain damage. Other common symptoms include PEO, general muscle weakness, exercise intolerance, hearing loss, diabetes and short stature. Failure of energy production due to faulty mitochondria and overproduction of ROS is a common feature of the disease.
In addition to energy failure and oxidative stress, there has been growing evidence that nitric oxide (NO) deficiency play a central role in the pathogenesis of the stroke-like episodes. Arginine is the substrate of nitric oxide synthase, which produces NO, therefore arginine is a promising treatment for MELAS patients (trial numbers NCT01603446, JMA-IIA00023, and JMA-IIA00025. Other studies in their preliminary stages have shown more potent effect of citrulline than L-arginine in stroke-like episodes in MELAS patients (NCT01339494). Some of the other molecules investigated in clinical trials for patients with MELAS include pyruvate (JMA-IIA00093), taurine (UMIN000011908), and supplemental medium chain triglycerides (NCT01252979); however, those results of trials are still pending.