LAUSR

Primary tauopathies are neurodegenerative diseases in which tau protein aggregates constitute the main underlying neuropathological process. Tau proteins are a group of six isomers that bind to and stabilize microtubules and play a role in axonal transport. Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are considered 4-repeat (4R) tauopathies based on the predominant tau isomer in the aggregates, and there are currently no effective pharmacological treatments for these disorders. Experimental therapeutic trials designed to slow or halt disease progression have mostly been conducted for PSP and less frequently for CBD. Although several promising disease-modifying drugs of different targets and proven efficacy on animal models have been implemented in well-designed human clinical trials (Fig. 1), all have failed to slow or halt disease progression. In view of the wide gap between basic research and its translation into clinic, here we reviewed relevant experimental therapeutic trial steps, including participant selection, therapeutic targets, and experimental platforms. Key considerations for advancing the translation of future therapeutic approaches into successful disease-modifying agents are provided (Table 1).