Pilot Study to Investigate the Efficacy of L-arginine Therapy on Endothelium-dependent Vasodilation & Mitochondrial Metabolism in MELAS Syndrome.

We will study a family of 3 siblings, each with different severities of MELAS, using safe, non-invasive tests. We will determine whether there is a decrease in the ability of small brain blood vessels to increase blood flow by dilating in response to certain stimuli such as increased blood carbon dioxide levels or in response to brain cell activation in the vision centre by visual stimuli. We will use a technique called BOLD-fMRI which can detect changes in brain blood flow. As exercising muscle also depends on increased blood flow and mitochondrial energy, we will study different measures of aerobic energy metabolism in exercising muscle using cycle exercise testing and special phosphorus-magnetic resonance spectroscopy which measures the changes in the major chemicals of muscle energy metabolism. The dietary amino acid L-arginine is known to dilate blood vessels increasing blood flow and to decrease toxic free radicals that are generated by dysfunctional mitochondria. We will determine the effect of a single dose and a 6 week trial of oral L-arginine, on brain blood vessel reactivity, brain cell activation and muscle aerobic function to see how useful this would be in the treatment of these patients and other mitochondrial disorders which present with strokes.