26 July 2021: Editorial
Editorial: Targets for Disease-Modifying Therapies in Alzheimer’s Disease, Including Amyloid β and Tau ProteinDinah V. Parums *
Med Sci Monit 2021; 27:e934077
ABSTRACT: Current treatments for patients with Alzheimer’s disease aim to improve behavioral, cognitive, and non-cognitive symptoms. There have been no new drug approvals for preventing or treating Alzheimer’s disease for more than two decades. Drug development in Alzheimer’s disease aims to identify disease-modifying therapies that will delay or slow the clinical course of this disease. More than 50% of the current Alzheimer’s disease drug pipeline now involves immunotherapies or oral small molecule agents. The most promising disease-modifying drug targets are amyloid β and tau protein. In June 2021, aducanumab, a humanized recombinant monoclonal antibody to amyloid β, was the first potential disease-modifying therapy approved by the US Food and Drug Administration (FDA) to treat Alzheimer’s disease and mild cognitive impairment. Accelerated approval of aducanumab was based on the results of only one of two phase 3 clinical trials. Several clinical trials of targeted disease-modifying immunotherapies to the tau protein and amyloid β that commenced before the current COVID-19 pandemic have been delayed. This Editorial aims to provide an update on past, present, and future disease-modifying therapies in Alzheimer’s disease, including targeted therapies for amyloid β and tau protein.
Keywords: Editorial, Alzheimer Disease, Amyloid beta-Peptides, tau Proteins, Immunotherapy, Clinical Trial
In the past decade, there has been an increased understanding of potential targets for disease-modifying therapies that will delay or slow the clinical course of Alzheimer’s disease, in addition to amyloid β and tau protein. Despite the controversy associated with the recent accelerated approval of aducanumab and the effects of the COVID-19 pandemic on the progress of clinical trials, the range of potential disease-modifying therapies in Alzheimer’s disease may lead to future further approvals.
1. Scheltens P, Blennow K, Breteler MM: Alzheimer’s disease: Lancet, 2018; 388; 505-517
2. Lane CA, Hardy J, Schott JM: Alzheimer’s disease: Eur J Neurol, 2018; 25(1); 59-70
3. Jack CR, Knopman DS, Jagust WJ: Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers: Lancet Neurol, 2013; 12(2); 207-16
4. Sosa-Ortiz AL, Acosta-Castillo I, Prince MJ: Epidemiology of dementias and Alzheimer’s disease: Arch Med Res, 2012; 43(8); 600-8
5. Sosa-Ortiz AL, Acosta-Castillo I, Prince MJ: 2021 Alzheimer’s disease facts and figures: Alzheimers Dement, 2021; 17(3); 327-406
6. Qaseem A, Snow V, Cross JT: Current pharmacologic treatment of dementia: A clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians: Ann Intern Med, 2008; 148; 370
7. Birks J: Cholinesterase inhibitors for Alzheimer’s disease: Cochrane Database Syst Rev, 2006(1); CD005593
8. McShane R, Areosa Sastre A, Minakaran N: Memantine for dementia: Cochrane Database Syst Rev, 2006(2); CD003154
9. Cummings J, Lee G, Ritter A: Alzheimer’s disease drug development pipeline: 2020: Alzheimers Dement (NY), 2020; 6(1); e12050
10. Sevigny J, Chiao P, Bussière T: The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease: Nature, 2016; 537; 50
11. Kuller LH, Lopez OL: ENGAGE and EMERGE: Truth and consequences?: Alzheimers Dement, 2021; 17(4); 692-95
12. Cao J, Hou J, Ping J, Cai D: Advances in developing novel therapeutic strategies for Alzheimer’s disease: Mol Neurodegener, 2018; 13(1); 64
13. Cao J, Hou J, Ping J, Cai D:: Food and Drug Administration (FDA) News Release, 2021
14. Walsh S, Merrick R, Milne R, Brayne C: Aducanumab for Alzheimer’s disease?: BMJ, 2021; 374; n1682
15. Alexander GC, Emerson S, Kesselheim AS: Evaluation of aducanumab for Alzheimer disease: Scientific evidence and regulatory review involving efficacy, safety, and futility: JAMA, 2021; 325; 1717
16. Schneider L: A resurrection of aducanumab for Alzheimer’s disease: Lancet Neurol, 2020; 19; 111
17. Schneider L: AduhelmTM (aducanumab-avwa) injection, for intravenous use: Initial US
18. Sperling RA, Jack CR, Black SE: Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: Recommendations from the Alzheimer’s Association Research Roundtable Workgroup: Alzheimers Dement, 2011; 7; 367
19. Vogel JW, Young AL, Oxtoby NP: Four distinct trajectories of tau deposition identified in Alzheimer’s disease: Nat Med, 2021; 27(5); 871-81
20. Bejanin A, Schonhaut DR, La Joie R: Tau pathology and neurodegeneration contribute to cognitive impairment in Alzheimer’s disease: Brain, 2017; 140(12); 3286-300
21. Marasco RA: Current and evolving treatment strategies for the Alzheimer disease continuum: Am J Manag Care, 2020; 26(8 Suppl); S167-76
22. West T, Hu Y, Verghese PB: Preclinical and clinical development of ABBV-8E12, a humanized anti-tau antibody, for treatment of Alzheimer’s disease and other tauopathies: J Prev Alzheimers Dis, 2017; 4(4); 236-41
23. Qureshi IA, Tirucherai G, Ahlijanian MK: A randomized, single ascending dose study of intravenous BIIB092 in healthy participants: Alzheimers Dement (NY), 2018; 4; 746-55
24. Ayalon G, Lee SH, Adolfsson O: Antibody semorinemab reduces tau pathology in a transgenic mouse model and engages tau in patients with Alzheimer’s disease: Sci Transl Med, 2021; 13(593); eabb2639
25. Vaz M, Silvestre S: Alzheimer’s disease: Recent treatment strategies: Eur J Pharmacol, 2020; 887; 173554
26. Novak P, Schmidt R, Kontsekova E: Safety and immunogenicity of the tau vaccine AADvac1 in patients with Alzheimer’s disease: A randomised, double-blind, placebo-controlled, phase 1 trial: Lancet Neurol, 2017; 16(2); 123-34
27. Novak P, Kontsekova E, Zilka N, Novak M: Ten years of tau-targeted immunotherapy: The path walked and the roads ahead: Front Neurosci, 2018; 12; 798
28. Refolo LM, Snyder H, Liggins C: Common Alzheimer’s disease research ontology: National Institute on Aging and Alzheimer’s Association collaborative project: Alzheimers Dement, 2012; 8; 372-75
29. Refolo LM, Snyder H, Liggins C:: International Alzheimer’s and Related Dementias Research Portfolio: Common Alzheimer’s and Related Dementias Research Ontology (CADRO), 2020
30. Jack CR, Bennett DA, Blennow K: NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease: Alzheimers Dement, 2018; 14(4); 535-62
31. Jack CR, Bennett DA, Blennow K: Early Alzheimer’s disease: Developing drugs for treatment: Guidance for industry, 2018
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