Advancements in Pharmacological Treatment of Alzheimer's Disease: The Advent of Disease-Modifying Therapies (DMTs)

Overview

Journal Brain Sci

Publisher MDPI

Date 2024 Oct 25

PMID 39452004

Authors

Qiong Wang

Sihui Chen

Junhui Wang

Huifang Shang

Xueping Chen

Affiliations

Soon will be listed here.

Abstract

The landscape of pharmacological treatment for Alzheimer's disease (AD) has undergone significant transformations with the advent of disease-modifying therapies (DMTs) targeting β-Amyloid (Aβ) accumulation, one of the hallmark pathologies of AD. The approval and market introduction of monoclonal antibodies mark the dawn of a new era in AD therapeutics as well. Furthermore, considerable progress has also been made in the development of new drugs targeting non-Aβ and non-Tau protein pathways. These advancements are key in tackling the root causes of AD, offering hope for treatments that both relieve symptoms and slow disease progression, improving patient outcomes and quality of life. This review aims to provide a comprehensive update on the advances in drug development and application for AD, including those currently in clinical trials and those already approved for the market to treat patients.

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References

Reisberg B, Doody R, Stoffler A, Schmitt F, Ferris S, Mobius H . Memantine in moderate-to-severe Alzheimer's disease. N Engl J Med. 2003; 348(14):1333-41. DOI: 10.1056/NEJMoa013128. View

Tabor G, Holtzman D . Current status of amyloid-targeting immunotherapies for Alzheimer's disease. Sci Transl Med. 2023; 15(721):eadk9993. DOI: 10.1126/scitranslmed.adk9993. View

Wang Y, Mandelkow E . Tau in physiology and pathology. Nat Rev Neurosci. 2015; 17(1):5-21. DOI: 10.1038/nrn.2015.1. View

Walker J, Pacoma R, Watson J, Ou W, Alves J, Mason D . Enhanced proteolytic clearance of plasma Aβ by peripherally administered neprilysin does not result in reduced levels of brain Aβ in mice. J Neurosci. 2013; 33(6):2457-64. PMC: 6619149. DOI: 10.1523/JNEUROSCI.3407-12.2013. View

Jucker M, Walker L . Pathogenic protein seeding in Alzheimer disease and other neurodegenerative disorders. Ann Neurol. 2011; 70(4):532-40. PMC: 3203752. DOI: 10.1002/ana.22615. View

Wang H, Cecon E, Dam J, Pei Z, Jockers R, Burns L . Simufilam Reverses Aberrant Receptor Interactions of Filamin A in Alzheimer's Disease. Int J Mol Sci. 2023; 24(18). PMC: 10531384. DOI: 10.3390/ijms241813927. View

The Lancet . Lecanemab for Alzheimer's disease: tempering hype and hope. Lancet. 2022; 400(10367):1899. DOI: 10.1016/S0140-6736(22)02480-1. View

Rezai A, DHaese P, Finomore V, Carpenter J, Ranjan M, Wilhelmsen K . Ultrasound Blood-Brain Barrier Opening and Aducanumab in Alzheimer's Disease. N Engl J Med. 2024; 390(1):55-62. DOI: 10.1056/NEJMoa2308719. View

Wiser I, Balicer R, Cohen D . An update on smallpox vaccine candidates and their role in bioterrorism related vaccination strategies. Vaccine. 2006; 25(6):976-84. DOI: 10.1016/j.vaccine.2006.09.046. View

10.

Christ M, Huesmann H, Nagel H, Kern A, Behl C . Sigma-1 Receptor Activation Induces Autophagy and Increases Proteostasis Capacity In Vitro and In Vivo. Cells. 2019; 8(3). PMC: 6468724. DOI: 10.3390/cells8030211. View

11.

Ettcheto M, Cano A, Sanchez-Lopez E, Verdaguer E, Folch J, Auladell C . Masitinib for the treatment of Alzheimer's disease. Neurodegener Dis Manag. 2021; 11(4):263-276. DOI: 10.2217/nmt-2021-0019. View

12.

Reading C, Ahlem C, Murphy M . NM101 Phase III study of NE3107 in Alzheimer's disease: rationale, design and therapeutic modulation of neuroinflammation and insulin resistance. Neurodegener Dis Manag. 2021; 11(4):289-298. DOI: 10.2217/nmt-2021-0022. View

13.

Mangialasche F, Solomon A, Winblad B, Mecocci P, Kivipelto M . Alzheimer's disease: clinical trials and drug development. Lancet Neurol. 2010; 9(7):702-16. DOI: 10.1016/S1474-4422(10)70119-8. View

14.

Novak P, Kovacech B, Katina S, Schmidt R, Scheltens P, Kontsekova E . ADAMANT: a placebo-controlled randomized phase 2 study of AADvac1, an active immunotherapy against pathological tau in Alzheimer's disease. Nat Aging. 2023; 1(6):521-534. DOI: 10.1038/s43587-021-00070-2. View

15.

Yang Y, Qiu H, Fan Y, Zhang Q, Qin H, Wu J . Safety, tolerability, pharmacokinetics and pharmacodynamics of a single intravenous dose of SHR-1707 in healthy adult subjects: two randomized, double-blind, single-ascending-dose, phase 1 studies. Alzheimers Res Ther. 2024; 16(1):218. PMC: 11465679. DOI: 10.1186/s13195-024-01584-8. View

16.

Cummings J, Leisgang Osse A, Cammann D, Powell J, Chen J . Anti-Amyloid Monoclonal Antibodies for the Treatment of Alzheimer's Disease. BioDrugs. 2023; 38(1):5-22. PMC: 10789674. DOI: 10.1007/s40259-023-00633-2. View

17.

Ryskamp D, Korban S, Zhemkov V, Kraskovskaya N, Bezprozvanny I . Neuronal Sigma-1 Receptors: Signaling Functions and Protective Roles in Neurodegenerative Diseases. Front Neurosci. 2019; 13:862. PMC: 6736580. DOI: 10.3389/fnins.2019.00862. View

18.

Zhao Z, Liu Y, Ruan S, Hu Y . Current Anti-Amyloid-β Therapy for Alzheimer's Disease Treatment: From Clinical Research to Nanomedicine. Int J Nanomedicine. 2023; 18:7825-7845. PMC: 10749171. DOI: 10.2147/IJN.S444115. View

19.

Congdon E, Ji C, Tetlow A, Jiang Y, Sigurdsson E . Tau-targeting therapies for Alzheimer disease: current status and future directions. Nat Rev Neurol. 2023; 19(12):715-736. PMC: 10965012. DOI: 10.1038/s41582-023-00883-2. View

20.

Barakos J, Sperling R, Salloway S, Jack C, Gass A, Fiebach J . MR imaging features of amyloid-related imaging abnormalities. AJNR Am J Neuroradiol. 2013; 34(10):1958-65. PMC: 7965435. DOI: 10.3174/ajnr.A3500. View