Clinical development of passive tau-based immunotherapeutics for treating primary and secondary tauopathies

Francesco Panza, Vittorio Dibello, Rodolfo Sardone, Fabio Castellana, Roberta Zupo, Luisa Lampignano, Ilaria Bortone, Roberta Stallone, Nicoletta Cirillo, Christian Damiani, Mario Altamura, Antonello Bellomo, Antonio Daniele, Vincenzo Solfrizzi, Madia Lozupone

Research output: Contribution to journalArticle

Abstract

IntroductionTauopathies are clinicopathological entities with increased and pathological deposition in glia and/or neurons of hyperphosphorylated aggregates of the microtubule-binding protein tau. In secondary tauopathies, i.e. Alzheimer's disease (AD), tau deposition can be observed, but tau coexists with another protein (amyloid-& beta;). In the last 20 years, little progress has been made in developing disease-modifying drugs for primary and secondary tauopathies and available symptomatic drugs have limited efficacy.Areas coveredThe present review summarized recent advances about the development and challenges in treatments for primary and secondary tauopathies, with a focus on passive tau-based immunotherapy.Expert opinionSeveral tau-targeted passive immunotherapeutics are in development for treating tauopathies. At present, 14 anti-tau antibodies have entered clinical trials, and 9 of them are still in clinical testing for progressive supranuclear palsy syndrome and AD (semorinemab, bepranemab, E2814, JNJ-63733657, Lu AF87908, APNmAb005, MK-2214, PNT00, and PRX005). However, none of these nine agents have reached Phase III. The most advanced anti-tau monoclonal antibody for treating AD is semorinemab, while bepranemab is the only anti-tau monoclonal antibody still in clinical testing for treating progressive supranuclear palsy syndrome. Further evidence on passive immunotherapeutics for treating primary and secondary tauopathies will come from ongoing Phase I/II trials.
Original languageEnglish
Pages (from-to)625-634
Number of pages20
JournalExpert Opinion on Investigational Drugs
Volume32
DOIs
Publication statusPublished - 2023

Keywords

  • Alzheimer’s disease
  • FTLD-Tau
  • PSPS
  • tauopathies
  • mild cognitive impairment
  • monoclonal antibodies
  • tau
  • dementia

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