Objective: The primary cause for stroke-like episodes (SLE) in MELAS patients, whether mitochondrial cytopathy, angiopathy, or both, remains controversial. We reported that MELAS is associated with endothelial dysfunction. Using L-arginine, a potent donor of nitric oxide at physiological condition, we need to evaluate their efficacy for therapeutic purpose. Since we do not have a useful biomarker for mitochondrial disorders, we have been investigated clinically useful biomarkers for diagnostic, evaluate the severity and therapeutic efficacy. 

Methods: We have evaluated the efficacy of L-arginine for MELAS weather it is useful for cure the symptoms associate with SLE at acute phase, or for protect the SLE at intrinsic phase of MELAS using investigator-mediated clinical trial in Japan. To identify novel biomarkers for the diagnosis, we have performed microarray analysis of 2SD cybrid cells harbouring a MELAS-causing mutation and control cells treated with either lactate or pyruvate. We also investigated the clinical application of GDF15 in the daily practise. Results: We have established the therapeutic regimen to cure the symptoms associated with SLE, and to protect SLE in the intrinsic phase in MELAS. The systematic administration of oral and intravenous L-arginine may be therapeutically beneficial and clinically useful for patients with MELAS. GDF15, a new biomarker, could be a useful marker for diagnosis, evaluation the severity of the disease, and therapeutic efficacy for mitochondrial disorders. Conclusions: The therapeutic regimen using L-arginine is useful for maintaining good quality of life in MELAS. A new biomarker GDF15 is very useful for daily practice in patient care of mitochondrial disorders. We are now developing the automated inspection device for GDF15 for the universal testing in the hospital.