Efficacy of pyruvate therapy in patients with mitochondrial disease: a semi-quantitative clinical evaluation study.
BACKGROUND
Disorders of oxidative phosphorylation (OXPHOS) cause an increase in the NADH/NAD(+) ratio, which impairs the glycolysis pathway. Treatment with pyruvate is expected to decrease the ratio and thereby restore glycolysis. There are some case reports on the efficacy of pyruvate treatment for mitochondrial diseases. However, few of these reports assessed their results using a standardized scale.


METHODS
We monitored 4 bedridden patients with OXPHOS disorders who continued therapies of 0.5-1.0 g/kg/day of sodium pyruvate for more than 12 months. The efficacies of these treatments were evaluated with the Newcastle Pediatric Mitochondrial Disease Scale and the Gross Motor Function Measure with 88 items.


RESULTS
The ages of the patients at the treatment initiation ranged from 8-100 months. Of the 4 patients, 3 exhibited improvements within 1-3 months from the initiation of treatment. Among these 3 patients, one maintained the improvement for over 2 years. The remaining 2 regressed 3-6 months after the initiation of treatment. The blood lactate/pyruvate ratios did not correlate with the efficacy of treatment.


CONCLUSIONS
Pyruvate was effective even in bedridden patients with OXPHOS disorders, at least in the short term. Clinical trials with more patients and less severe disabilities are necessary to evaluate the long-term efficacy of this treatment. Biomarkers other than lactate and pyruvate need to be identified to biochemically monitor the efficacy of this treatment.
Department of Pediatrics, Shiga Medical Center for Children, 5-7-30 Moriyama, Shiga 524-0022, Japan. Electronic address: tatsufu@gmail.com.
Tatsuya
T
Fujii
Department of Pediatrics, Shiga Medical Center for Children, 5-7-30 Moriyama, Shiga 524-0022, Japan.
Fumihito
F
Nozaki
Department of Pediatrics, Shiga Medical Center for Children, 5-7-30 Moriyama, Shiga 524-0022, Japan.
Keiko
K
Saito
Department of Pediatrics, Shiga Medical Center for Children, 5-7-30 Moriyama, Shiga 524-0022, Japan.
Anri
A
Hayashi
Department of Genomics for Longevity and Health, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakane-cho, Itabashi, Tokyo 173-0015, Japan.
Yutaka
Y
Nishigaki
Department of Metabolism, Chiba Children's Hospital, 579-1 Heta-cho, Midori, Chiba 266-0007, Japan.
Kei
K
Murayama
Department of Genomics for Longevity and Health, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakane-cho, Itabashi, Tokyo 173-0015, Japan.
Masashi
M
Tanaka
Department of Pediatrics and Child Health, Kurume University Graduate School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan.
Yasutoshi
Y
Koga
Department of Pediatrics, Shiga Medical Center for Children, 5-7-30 Moriyama, Shiga 524-0022, Japan.
Ikuko
I
Hiejima
Department of Pediatrics, Shiga Medical Center for Children, 5-7-30 Moriyama, Shiga 524-0022, Japan.
Tomohiro
T
Kumada
D002648:Child; D004334:Drug Administration Schedule; D005260:Female; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D007223:Infant; D019344:Lactic Acid / Q000097:blood; D008297:Male; D028361:Mitochondrial Diseases / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D019289:Pyruvic Acid / Q000008:administration & dosage* / Q000627:therapeutic use; D016896:Treatment Outcome
D019344:Lactic Acid; D019289:Pyruvic Acid
Lactate-to-pyruvate ratio; Mitochondrial disease; NAD(+); Pyruvate; Therapy