The therapeutic landscape of tauopathies: challenges and prospects

Tauopathies are a group of neurodegenerative disorders characterized by the aggregation of the microtubule-associated protein tau. Aggregates of misfolded tau protein are believed to be implicated in neuronal death, which leads to a range of symptoms including cognitive decline, behavioral change, dementia, and motor deficits. Currently, there are no effective treatments for tauopathies. There are four clinical candidates in phase III trials and 16 in phase II trials. While no effective treatments are currently approved, there is increasing evidence to suggest that various therapeutic approaches may slow the progression of tauopathies or improve symptoms. This review outlines the landscape of therapeutic drugs (indexed through February 28, 2023) that target tau pathology and describes drug candidates in clinical development as well as those in the discovery and preclinical phases. The review also contains information on notable therapeutic programs that are inactive or that have been discontinued from development.