Biomarkers and two clinical rating scales-the Japanese
mitochondrial disease-rating scale (JMDRS) and Newcastle
mitochondrial disease adult scale (NMDAS)-are clinically used when treating patients with
mitochondrial disease. We explored the
biomarker(s) and clinical rating scale(s) that are appropriate in preparing the protocol for a future clinical trial of
sodium pyruvate (SP)
therapy. A 48-week, prospective, single-centre, exploratory, clinical study enrolled 11 Japanese adult patients with genetically, biochemically, and clinically confirmed
mitochondrial disease; they had intractable
lactic acidosis and received SP (0.5 g/kg t.i.d. PO). Plasma concentrations of
lactate and
pyruvate, lateral ventricular levels of
lactate, and serum concentrations of
growth differentiation factor 15 (GDF15) and
fibroblast growth factor 21 were measured at baseline and at weeks 12 and 48 of SP
therapy. At week 48, plasma
lactate (P = .004), the
lactate/
pyruvate ratio (P = .012), serum GDF15 (P = .020), and lateral ventricular
lactate (P = .038) decreased significantly from the baseline values; the JMDRS and NMDAS scores did not decrease significantly, although the NMDAS overall score showed a strong tendency (P = .059). Two patients with end-stage
MELAS at baseline died during SP
therapy. The present study showed significant decreases in plasma and lateral ventricular
lactate, the L/P ratio, and serum GDF15. Therefore, the protocol for a future clinical study of SP
therapy in this patient population needs to include plasma and lateral ventricular
lactate, the L/P ratio, and serum GDF15 as diagnostic indicators, and exclude patients with end-stage
mitochondrial disease.