A walk through tau therapeutic strategies

Santosh Jadhav,
Jesus Avila,
Michael Schöll,
Gabor G. Kovacs,
Enikö Kövari,
Rostislav Skrabana,
Lewis D Evans,
Eva Kontsekova,
Barbara Malawska,
Rohan de Silva,
Luc BueeEmail author View ORCID ID profile and
Norbert ZilkaEmail author

Acta Neuropathologica Communications20197:22

https://doi.org/10.1186/s40478-019-0664-z

Received: 30 November 2018
Accepted: 21 January 2019
Published: 15 February 2019

Abstract

Tau neuronal and glial pathologies drive the clinical presentation of Alzheimer’s disease and related human tauopathies. There is a growing body of evidence indicating that pathological tau species can travel from cell to cell and spread the pathology through the brain. Throughout the last decade, physiological and pathological tau have become attractive targets for AD therapies. Several therapeutic approaches have been proposed, including the inhibition of protein kinases or protein-3-O-(N-acetyl-beta-D-glucosaminyl)-L-serine/threonine Nacetylglucosaminyl hydrolase, the inhibition of tau aggregation, active and passive immunotherapies, and tau silencing by antisense oligonucleotides. New tau therapeutics, across the board, have demonstrated the ability to prevent or reduce tau lesions and improve either cognitive or motor impairment in a variety of animal models developing neurofibrillary pathology. The most advanced strategy for the treatment of human tauopathies remains immunotherapy, which has already reached the clinical stage of drug development. Tau vaccines or humanised antibodies target a variety of tau species either in the intracellular or extracellular spaces. Some of them recognise the amino-terminus or carboxy-terminus, while others display binding abilities to the proline-rich area or microtubule binding domains. The main therapeutic foci in existing clinical trials are on Alzheimer’s disease, progressive supranuclear palsy and non-fluent primary progressive aphasia. Tau therapy offers a new hope for the treatment of many fatal brain disorders. First efficacy data from clinical trials will be available by the end of this decade.