Progressive supranuclear palsy (PSP) is a rare
neurodegenerative disease characterized by the accumulation of
tau protein aggregates in the basal ganglia, brainstem and cerebral cortex leading to rapid
disease progression and death. The neurofibrillary tangles that define the neuropathology of PSP are comprised of aggregated 4R tau and show a well-defined distribution. Classically, PSP is diagnosed by symptoms that include progressive gait disturbance, early falls, vertical
ophthalmoparesis, akinetic-rigid features, prominent bulbar dysfunction and fronto-subcortical
dementia. There are currently no effective
therapies for the treatment of this rapidly degenerating and debilitating disease.
Davunetide is a novel neuroprotective
peptide that is thought to impact neuronal integrity and cell survival through the stabilization of microtubules. Preclinical activity in models of
tauopathy has been translated to clinical studies, demonstrating pharmacologic activity that has supported further development.
Davunetide's efficacy and tolerability are being tested in a placebo-controlled study in PSP patients, making it the most advanced
drug candidate in this indication. This review examines the disease characteristics of PSP, the rationale for treating PSP with
davunetide and assesses some of the challenges of clinical trials in this patient population.