Disease-Modifying Treatments for Progressive Supranuclear Palsy

In recent years, research has focused on the development of disease-modifying treatments for PSP, targeting mainly at tau dysfunction. However, the glycogen synthase kinase 3 inhibitor, tideglusib, and the microtubuli stabilizer, davunetide, both failed to show efficacy in recent double-blind, placebo-controlled studies. Despite these results, further agents targeting tau dysfunction, tau post-translational modifications, or aiming at mictorubuli stabilization are currently being investigated. Further approaches under development include agents to reduce tau levels extracellularly by active or passive immunization, antisense oligonucleotides to reduce tau concentrations, and small interfering RNAs to suppress human tau expression. However, the major limitation on the way to find disease-modifying treatments for PSP still remains the lack of biomarkers. Indeed, for all of these potential therapeutic modalities, a well-designed human trial would require validated biomarkers, without which the results of negative efficacy trials will be difficult to interpret. In this regard, PET imaging using tau-specific ligands may be proven useful in the near future. There is great hope that the next decade will bring the first effective therapy for PSP.