Short-term effects of coenzyme Q₁₀ in progressive supranuclear palsy: A randomized, placebo-controlled trial

Mitochondrial complex I appears to be dysfunctional in progressive supranuclear palsy (PSP). Coenzyme Q₁₀ (CoQ₁₀) is a physiological cofactor of complex I. Therefore, we evaluated the short-term effects of CoQ₁₀ in PSP. We performed a double-blind, randomized, placebo-controlled, phase II trial, including 21 clinically probable PSP patients (stage ≤ III) to receive a liquid nanodispersion of CoQ₁₀ (5 mg/kg/day) or matching placebo. Over a 6-week period, we determined the change in CoQ₁₀ serum concentration, cerebral energy metabolites (by ³¹P- and ¹H-magnetic resonance spectroscopy), motor and neuropsychological dysfunction (PSP rating scale, UPDRS III, Hoehn and Yahr stage, Frontal Assessment Battery, Mini Mental Status Examination, Montgomery Åsberg Depression Scale). CoQ₁₀ was safe and well tolerated. In patients receiving CoQ₁₀ compared to placebo, the concentration of low-energy phosphates (adenosine-diphosphate, unphosphorylated creatine) decreased. Consequently, the ratio of high-energy phosphates to low-energy phosphates (adenosine-triphosphate to adenosine-diphosphate, phospho-creatine to unphosphorylated creatine) increased. These changes were significant in the occipital lobe and showed a consistent trend in the basal ganglia. Clinically, the PSP rating scale and the Frontal Assessment Battery improved slightly, but significantly, upon CoQ₁₀ treatment compared to placebo. Since CoQ₁₀ appears to improve cerebral energy metabolism in PSP, long-term treatment might have a disease-modifying neuroprotective effect.