Investigating metabolic dependencies in human myopathies


Translational Research

Poster Number: 326


Claire Llamas, Children's Research Institute at UT Southwestern Medical Center, Salman Bhai, MD, Department of Neurology at UT Southwestern Medical Center, Prashant Mishra, MD, PhD, Children's Research Institute at UT Southwestern Medical Center

Metabolic alterations are a hallmark of human diseases, but the extent to which they drive pathology and represent a therapeutic opportunity are largely unknown. Recent advantages in 13C and 2H isotope tracing techniques have allowed investigations of metabolic fluxes not only in animal models of disease, but also in humans undergoing surgical procedures. These studies emphasize the importance of evaluating the metabolism of human diseases in their native setting. To do this, we recently implemented a human infusion protocol to assess metabolic changes in normal and myopathic patients undergoing outpatient muscle biopsy procedures. In our initial cohort, we identify changes in nutrient contribution to glycolytic and mitochondrial metabolites among myopathic patients which we correlate with histological analysis of muscle and in vitro measurements of mitochondrial activity. Our results suggest that isotope infusion protocols can be safely coupled with standard-of-care biopsies to evaluate altered nutrient metabolism in human myopathy.