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

  • Expert Opin Investig Drugs. 2023 Jul-Dec;32(7):625-634. doi: 10.1080/13543784.2023.2233892.
Francesco Panza  1  2 ,  Vittorio Dibello  2  3 ,  Rodolfo Sardone  2  4 ,  Fabio Castellana  2 ,  Roberta Zupo  1 ,  Luisa Lampignano  2 ,  Ilaria Bortone  2 ,  Roberta Stallone  5 ,  Nicoletta Cirillo  1 ,  Christian Damiani  1 ,  Mario Altamura  6 ,  Antonello Bellomo  6 ,  Antonio Daniele  7  8 ,  Vincenzo Solfrizzi  1 ,  Madia Lozupone  9
Affiliations
  • 1. Dipartimento Interdisciplinare di Medicina, Clinica Medica E Geriatria "Cesare Frugoni", University of Bari Aldo Moro, Bari, Italy.
  • 2. Unit of Research Methodology and Data Sciences for Population Health, National Institute of Gastroenterology "Saverio de Bellis" Research Hospital, Bari, Italy.
  • 3. Department of Orofacial Pain and Dysfunction, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
  • 4. Local Healthcare Authority of Taranto, Taranto, Italy.
  • 5. Neuroscience and Education, Human Resources Excellence in Research, University of Foggia, Foggia, Italy.
  • 6. Psychiatric Unit, Department of Clinical & Experimental Medicine, University of Foggia, Foggia, Italy.
  • 7. Department of Neuroscience, Catholic University of Sacred Heart, Rome, Italy.
  • 8. Neurology Unit, IRCCS Fondazione Policlinico Universitario A. Gemelli, Rome, Italy.
  • 9. Department of Translational Biomedicine and Neuroscience "DiBrain", University of Bari Aldo Moro, Bari, Italy.
PMID: 37405389 DOI: 10.1080/13543784.2023.2233892
Abstract

Introduction: Tauopathies 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-β). 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 covered: The 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 opinion: Several 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.

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