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.