Biomarkers of disease progression in progressive supranuclear palsy for use in clinical trials

Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease with no current disease-modifying treatments approved. Longitudinal research and clinical trials for PSP are ongoing and require reliable measures that are sensitive to disease progression. Despite susceptibility to subjective limitations, clinical and cognitive assessments are the most used instruments in therapeutic trials in PSP. The objective of this review was to identify measures that have been studied longitudinally as measures of progression and are suitable for use as clinical trial endpoints. We reviewed the measures currently used as trial endpoints, identifying the clinical, cognitive, fluid and imaging measures that have previously been studied longitudinally, and discuss current diagnostic and emerging measures that are yet to be studied longitudinally but that may be sensitive to disease progression. We found that many fluid and imaging measures require further research to validate their use as longitudinal measures of change, including emerging measures that have not yet been studied specifically in PSP. We also summarize the sample size estimates required to detect changes in a two-arm, 52-week therapeutic trial and found that specific MRI volumes require the smallest sample sizes to detect change.