To determine whether certain platelets mitochondrial bioenergetic parameters differ in ALS patients from healthy controls and whether changes in these parameters over time correlate with clinical measures of disease progression.

The skeletal muscles, “end-organ”, are one of the earliest sites of pathology in ALS. Evidence of neuromuscular junction loss and mitochondrial perturbations manifests before motor neuron degeneration. These disturbances include depletion of muscle mitochondrial respiratory chain complexes (I & IV). Recent studies suggest that change in bioenergetic parameters in platelets can reflect mitochondrial dysfunction in skeletal muscles.

In this prospective study, we enrolled patients with definite or probable ALS based on the El Escorial criteria, in addition to age-matched healthy controls. ALS Functional Rating Scale-Revised (ALSFRS-R) was measured at baseline, three, and six months. At each study visit, platelet bioenergetic parameters were assessed including basal, ATP-linked, maximal, and non–mitochondrial oxygen consumption rates (OCR). We also measured the reserve capacity and proton leak rate, in addition to levels of the different mitochondrial enzyme complexes.

Platelets in ALS patients demonstrate decreased bioenergetic capacity compared to healthy subjects. The significant correlation between rate of decline in Complex-II activity and ALSFRS-R suggests that it can serve as a monitoring biomarker of disease progression in ALS.