NAD+ and Exercise in FA (ExRx in FA)

There is a critical knowledge gap regarding the best ways to intervene to increase aerobic capacity (VO2max on exercise testing) in FA. Exercise is the most potent known stimulus for increasing muscle mass and mitochondrial oxidative phosphorylation (OXPHOS) capacity, increasing VO2max, and increasing insulin sensitivity (Si); however, it has not been studied in FA. One adaptation seen in exercised muscles is an increase in muscle nicotinamide adenine dinucleotide (NAD+), a cofactor required for glycolytic and mitochondrial adenosine triphosphate (ATP) production. In skeletal- and cardiac muscle-specific frataxin (FXN) knock-out animals, NAD+ precursors rescued cardiac function to near-normal, additionally highlighting its translational potential in FA. Nicotinamide riboside (NR) is a NAD+ precursor currently available as a dietary supplement (Tru Niagen ®, ChromaDex, Irvine CA) that is expected to be safe and well-tolerated in adults and children. The central hypothesis of this study is that exercise + NR will increase skeletal muscle mitochondrial OXPHOS and increase muscle mass to increase VO2max in FA. The investigators expect that exercise + NR will also increase Si in this cohort.