Disease-modifying therapies for tauopathies: agents in the pipeline

Francesco Panza, Bruno P. Imbimbo, Madia Lozupone, Antonio Greco, Andrea Greco, Davide Seripa, Giancarlo Logroscino, Antonio Daniele, Carlo Colosimo

Risultato della ricerca: Contributo in rivistaArticolo in rivista

5 Citazioni (Scopus)

Abstract

Introduction: Tauopathies are heterogeneous clinicopathological entities characterized by abnormal neuronal and/or glial inclusions of the microtubule-binding protein tau. Primary tauopathies considered to be diseases correspond to a major class of frontotemporal lobar degeneration (FTLD) neuropathology (FTLD-Tau), including several forms of frontotemporal dementia (FTD) clinical syndromes. Little progress has been made in the past 20 years in developing effective disease-modifying drugs for primary tauopathies and available symptomatic treatments have limited efficacy. Areas covered: Potential disease-modifying drugs in clinical development to slow neuropathological progression of primary tauopathies. Expert opinion: Since the underlying pathology of primary tauopathies consists of abnormal tau protein aggregates, treatments are being developed to interfere with the aggregation process or to promote the clearance of this protein. Unfortunately, disease-modifying treatments remain years away as demonstrated by the recent negative Phase III findings of a tau aggregation inhibitor (LMTM) for treating the behavioral variant of FTD. Further evidence will come from ongoing Phase I/II trials on novel drugs and immunotherapeutics with various targets–prevention of deposition or removal of tau aggregates, inhibition of tau phosphorylation/acetylation, modulation of O-GlcNAcylation, activation of autophagy or ubiquitin-proteasome system pathways, and rescue of selected tau loss of function or suppression of tau gene expression.
Lingua originaleEnglish
pagine (da-a)397-408
Numero di pagine12
RivistaExpert Review of Neurotherapeutics
Volume19
DOI
Stato di pubblicazionePubblicato - 2019

Keywords

  • Dementia
  • aging-related tau astrogliopathy
  • corticobasal degeneration
  • frontotemporal dementia
  • frontotemporal lobar degeneration
  • primary age-related tauopathy
  • primary tauopathies
  • progressive supranuclear palsy
  • tau protein

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