Small-molecule hypoxia therapy in mitochondrial disease.

In this issue of Cell, Blume et al. provide compelling rationale for pursuing pharmacologic optimization of a small-molecule "HypoxyStat," which left-shifts the oxyhemoglobin dissociation curve in red blood cells in an attempt to induce an effective and sustained reduction of chronic tissue hyperoxia in primary mitochondrial disease (PMD) and was well-tolerated and effective for both pre-symptomatic and advanced disease treatment to extend survival and improve neurologic outcomes in a mouse model of Leigh syndrome spectrum.