Tau-Based Therapeutics for Alzheimer’s Disease: Active and Passive Immunotherapy

Abstract

Pharmacological manipulation of tau protein in Alzheimer’s disease included microtubule-stabilizing agents, tau protein kinase inhibitors, tau aggregation inhibitors, active and passive immunotherapies and, more recently, inhibitors of tau acetylation. Animal studies have shown that both active and passive approaches can remove tau pathology and, in some cases, improve cognitive function. Two active vaccines targeting either nonphosphorylated (AAD-vac1) and phosphorylated tau (ACI-35) have entered Phase I testing. Notwithstanding, the recent discontinuation of the monoclonal antibody RG7345 for Alzheimer’s disease, two other antitau antibodies, BMS-986168 and C2N-8E12, are also currently in Phase I testing for progressive supranuclear palsy. After the recent impressive results in animal studies obtained by salsalate, the dimer of salicylic acid, inhibitors of tau acetylation are being actively pursued.

Keywords::

• active immunotherapy
• Alzheimer’s disease
• passive immunotherapy

Financial & competing interests disclosure

This study was supported by ‘Ministero della Salute,’ I.R.C.C.S. Research Program, Ricerca Corrente 2015–2017, Linea n. 2 ‘Malattie complesse e terapie innovative,’ by the ‘5 × 1000’ voluntary contribution, and by Programmi di Ricerca Scientifica di Rilevante Interesse Nazionale (PRIN) 2009 Grant 2009E4RM4Z. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This study was supported by ‘Ministero della Salute,’ I.R.C.C.S. Research Program, Ricerca Corrente 2015–2017, Linea n. 2 ‘Malattie complesse e terapie innovative,’ by the ‘5 × 1000’ voluntary contribution, and by Programmi di Ricerca Scientifica di Rilevante Interesse Nazionale (PRIN) 2009 Grant 2009E4RM4Z. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.