Abstract
Mitochondrial complex I appears to be dysfunctional in progressive supranuclear palsy (PSP). Coenzyme Q~10~ (CoQ~10~) is a physiological cofactor of complex I. Therefore, we evaluated the short‐term effects of CoQ~10~ 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 CoQ~10~ (5 mg/kg/day) or matching placebo. Over a 6‐week period, we determined the change in CoQ~10~ serum concentration, cerebral energy metabolites (by ^31^P‐ and ^1^H‐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). CoQ~10~ was safe and well tolerated. In patients receiving CoQ~10~ 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 CoQ~10~ treatment compared to placebo. Since CoQ~10~ appears to improve cerebral energy metabolism in PSP, long‐term treatment might have a disease‐modifying, neuroprotective effect. © 2008 Movement Disorder Society