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Combination therapy in Alzheimer’s disease: is it time?

Combination therapy in Alzheimer’s disease: is it time?
Combination therapy in Alzheimer’s disease: is it time?
Alzheimer's disease (AD) is the most common cause of dementia globally. There is increasing evidence showing AD has no single pathogenic mechanism, and thus treatment approaches focusing only on one mechanism are unlikely to be meaningfully effective. With only one potentially disease modifying treatment approved, targeting amyloid-β (Aβ), AD is underserved regarding effective drug treatments. Combining multiple drugs or designing treatments that target multiple pathways could be an effective therapeutic approach. Considering the distinction between added and combination therapies, one can conclude that most trials fall under the category of added therapies. For combination therapy to have an actual impact on the course of AD, it is likely necessary to target multiple mechanisms including but not limited to Aβ and tau pathology. Several challenges have to be addressed regarding combination therapy, including choosing the correct agents, the best time and stage of AD to intervene, designing and providing proper protocols for clinical trials. This can be achieved by a cooperation between the pharmaceutical industry, academia, private research centers, philanthropic institutions, and the regulatory bodies. Based on all the available information, the success of combination therapy to tackle complicated disorders such as cancer, and the blueprint already laid out on how to implement combination therapy and overcome its challenges, an argument can be made that the field has to move cautiously but quickly toward designing new clinical trials, further exploring the pathological mechanisms of AD, and re-examining the previous studies with combination therapies so that effective treatments for AD may be finally found.
Alzheimer's disease, clinical trials, combination therapy, treatment
1387-2877
1433-1449
Salehipour, Arash
65c750de-59b0-42df-a3f3-7a7a8a7aae98
Bagheri, Motahareh
3bc85eb6-3450-445d-8b79-94e17f46cb1b
Sabahi, Mohammadmahdi
16160544-2f07-4b50-92b0-3a52a250d1bb
Dolatshahi, Mahsa
794dd41b-72b6-4c41-85f1-87c50ecc1a6a
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61
Salehipour, Arash
65c750de-59b0-42df-a3f3-7a7a8a7aae98
Bagheri, Motahareh
3bc85eb6-3450-445d-8b79-94e17f46cb1b
Sabahi, Mohammadmahdi
16160544-2f07-4b50-92b0-3a52a250d1bb
Dolatshahi, Mahsa
794dd41b-72b6-4c41-85f1-87c50ecc1a6a
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61

Salehipour, Arash, Bagheri, Motahareh, Sabahi, Mohammadmahdi, Dolatshahi, Mahsa and Boche, Delphine (2022) Combination therapy in Alzheimer’s disease: is it time? Journal of Alzheimer's Disease, 87 (4), 1433-1449. (doi:10.3233/JAD-215680).

Record type: Review

Abstract

Alzheimer's disease (AD) is the most common cause of dementia globally. There is increasing evidence showing AD has no single pathogenic mechanism, and thus treatment approaches focusing only on one mechanism are unlikely to be meaningfully effective. With only one potentially disease modifying treatment approved, targeting amyloid-β (Aβ), AD is underserved regarding effective drug treatments. Combining multiple drugs or designing treatments that target multiple pathways could be an effective therapeutic approach. Considering the distinction between added and combination therapies, one can conclude that most trials fall under the category of added therapies. For combination therapy to have an actual impact on the course of AD, it is likely necessary to target multiple mechanisms including but not limited to Aβ and tau pathology. Several challenges have to be addressed regarding combination therapy, including choosing the correct agents, the best time and stage of AD to intervene, designing and providing proper protocols for clinical trials. This can be achieved by a cooperation between the pharmaceutical industry, academia, private research centers, philanthropic institutions, and the regulatory bodies. Based on all the available information, the success of combination therapy to tackle complicated disorders such as cancer, and the blueprint already laid out on how to implement combination therapy and overcome its challenges, an argument can be made that the field has to move cautiously but quickly toward designing new clinical trials, further exploring the pathological mechanisms of AD, and re-examining the previous studies with combination therapies so that effective treatments for AD may be finally found.

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Revised_manuscript_v2 - Accepted Manuscript
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More information

Accepted/In Press date: 5 April 2022
e-pub ahead of print date: 27 April 2022
Published date: 14 June 2022
Additional Information: Publisher Copyright: © 2022 - IOS Press. All rights reserved.
Keywords: Alzheimer's disease, clinical trials, combination therapy, treatment

Identifiers

Local EPrints ID: 456757
URI: http://eprints.soton.ac.uk/id/eprint/456757
ISSN: 1387-2877
PURE UUID: a6a48887-c9fc-431d-bbd6-9fe559ffa712
ORCID for Delphine Boche: ORCID iD orcid.org/0000-0002-5884-130X

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Date deposited: 10 May 2022 16:55
Last modified: 17 Mar 2024 02:51

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Contributors

Author: Arash Salehipour
Author: Motahareh Bagheri
Author: Mohammadmahdi Sabahi
Author: Mahsa Dolatshahi
Author: Delphine Boche ORCID iD

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