Inhibition of the mammalian target of rapamycin (mTOR) pathway with rapamycin attenuates neurological symptoms and extends lifespan in a mouse model of mitochondrial disease (Science doi:10.1126/science.1244360).

Leigh syndrome is a mitochondrial disease caused by mutations in NADH dehydrogenase (ubiquinone) Fe-S protein 4 (Ndufs4) characterized by stunted growth, myopathy and neurological symptoms, and ultimately death at an early age. Mice lacking Ndufs4 shows many of these features, including neurodegeneration and early death.

Matt Kaeberlein and his colleagues report that daily treatment of these mice with rapamycin considerably extends lifespan, delays weight loss, improves motor function and reduces astrocyte and microglial activation in the central nervous system. Mice deficient for Ndufs4 develop progressive metabolic abnormalities. Rapamycin treatment decreased accumulation of glycolytic intermediates and increased free fatty acid levels. As there are currently no treatment options for these patients, these findings suggest that targeting of the mTOR pathway could be used to treat Leigh syndrome and other mitochondrial diseases.