This recent study uncovers a potential new therapy, improved an existing treatment, and identified a disease biomarker in mice with PDHD
Researchers at the Abimael Laboratory of Neurometabolism and the Neurometabolomics & Neuroinformatics core at Mount Sinai have discovered a potential new therapy, improved an existing treatment, and identified a disease biomarker in mice with pyruvate dehydrogenase deficiency (PDHD).
The study, “Imaging brain glucose metabolism in vivo reveals propionate as a major anaplerotic substrate in pyruvate dehydrogenase deficiency,” was recently published in Cell Metabolism.
The study revealed that propionate (a short-chain fatty acid that we can consume or produce through the gut microbiota) serves as a major anaplerotic substrate (a biosynthetic or precursor molecule from which other molecules can be generated) in the brain of mice with pyruvate dehydrogenase deficiency (PDHD), a mitochondrial disease that primarily affects the brain of affected children. Supplementation of propionate along with a modified ketogenic diet (a high fat, low-carbohydrate diet) started before conception, continued throughout pregnancy and after birth, prolonged lifespan and mildly improved neurological outcomes in PDHD mice. Elevated glucose uptake and glycolysis were also observed as indicators of disease progression.
“Our findings highlight the role of propionate in sustaining brain metabolism in PDHD. This discovery opens new avenues for therapeutic interventions that could improve the quality of life for patients suffering from this debilitating condition,” said Isaac Marin-Valencia, MD, Assistant Professor of Neurology, Pediatrics, Neuroscience, and Genetics and Genomic Sciences.