Biomarkers and clinical rating scales for sodium pyruvate therapy in patients with mitochondrial disease

Publication date: Available online 7 February 2019Source: MitochondrionAuthor(s): Yasutoshi Koga, Nataliya Povalko, Eisuke Inoue, Kazutaka Nashiki, Masashi TanakaAbstractBiomarkers 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 pre...
Source: Mitochondrion - Category: Biochemistry Source Type: research