Targeting tau: Clinical trials and novel therapeutic approaches

Neurosci Lett. 2020 Jul 13:731:134919. doi: 10.1016/j.neulet.2020.134919. Epub 2020 May 4.

Abstract

Tauopathies are a group of over 20 clinicopathological neurodegenerative diseases including Alzheimer's disease (AD), the most common type of dementia, progressive supranuclear palsy, Pick's disease, corticobasal degeneration, among others. Tauopathies are defined by neurodegeneration and the presence of tau aggregates in affected brains regions. Interestingly, regional tau aggregation burden correlates with clinical phenotype and predicts cognitive status. Autosomal dominant mutations in the MAPT gene lead to tau deposition and clinical FTD syndromes with cognitive, behavioral, and motor impairment. Polymorphisms in or around the MAPT gene have also been strongly linked to other proteinopathies including synucleinopathies. Taken together these findings suggests that tau plays a critical role in neurodegeneration and proteinopathies, supporting the idea that tau targeted approaches can be disease-modifying and lead to clinically meaningful benefits in slowing or reversing disease progression. Increasingly, human clinical trials are testing this hypothesis. This article reviews tau-targeted therapies tested in clinical trials as well as agents currently in active development based on publicly disclosed information. We describe the therapeutic approaches of these trials based on the potential pathogenic mechanism they target.

Keywords: Alzheimer's disease; Corticobasal degeneration; Frontotemporal dementia; Parkinsonism; Pick's disease; Progressive supranuclear palsy; Tau; Tauopathies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Brain / metabolism*
  • Brain / pathology
  • Clinical Trials as Topic
  • Frontotemporal Dementia / drug therapy*
  • Frontotemporal Dementia / metabolism
  • Frontotemporal Dementia / pathology
  • Humans
  • Tauopathies / drug therapy*
  • Tauopathies / metabolism
  • Tauopathies / pathology
  • tau Proteins / drug effects
  • tau Proteins / metabolism*

Substances

  • tau Proteins