TY - JOUR
T1 - Drug repurposing for Alzheimer’s disease
T2 - a Delphi consensus and stakeholder consultation
AU - Corbett, Anne
AU - Sultana, Janet
AU - Stych, Kate
AU - Mills, Roger
AU - Cummings, Jeff L.
AU - Williams, Gareth
AU - Ismail, Zahinoor
AU - Soto-Martin, Maria
AU - Mintzer, Jacobo
AU - Gauthier, Serge
AU - Greig, Nigel H.
AU - Noble, Wendy
AU - Killick, Richard
AU - Lai, Mitchell K.P.
AU - Routledge, Carol
AU - Walsh, Frank
AU - Fillit, Howard
AU - Aarsland, Dag
AU - Lane, Roger
AU - Mills, Kathryn
AU - Ballard, Clive
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/12
Y1 - 2025/12
N2 - Background: Alzheimer’s disease (AD) is an escalating global challenge, with more than 40 million people affected, and this number is projected to increase to more than 100 million by 2050. While amyloid-targeting antibody treatments (lecanemab and donanemab) are a significant step forward, the benefits of these therapies remain limited. This highlights the necessity for safe and effective compounds that offer greater therapeutic benefits to the majority of individuals with or at risk of AD. Drug repurposing allows for a cost-effective, time-efficient strategy to accelerate the availability of treatments, owing to the availability of safety information. Method: This study focuses on the third iteration of the Delphi consensus programme aimed at identifying new high-priority drug candidates for repurposing in AD. An international expert panel comprising academics, clinicians and industry representatives was convened. Through a combination of anonymized drug nominations, systemic evidence reviews, iterative consensus rankings, and lay advisory inputs, drug candidates were evaluated and ranked based on rational, non-clinical, and clinical evidence and overall safety profiles. Results: Among the 80 candidates that were nominated by the expert panel, seven underwent review, with only three candidates meeting the following consensus criteria of relevant mechanisms for targeting neurodegenerative pathways, non-clinical efficacy, and tolerability in older individuals. The three agents were: [1] the live attenuated herpes zoster (HZ) vaccine (Zostavax) [2], sildenafil, a phosphodiesterase-5 (PDE-5) inhibitor, and [3] riluzole, a glutamate antagonist. The HZ vaccine additionally offers potential for population-level dementia risk reduction. Conclusion: This Delphi consensus identified three high-priority drug repurposing candidates for AD with favourable safety profiles and mechanistic plausibility, which are considered suitable for pragmatic clinical trials, including remote or hybrid designs. The PROTECT platform, which supports international cohorts in the UK, Norway, and Canada, offers a well-established means to conduct such trials effectively, thus helping to accelerate the evaluation and potential deployment of these drug candidates to benefit individuals with or at risk for AD.
AB - Background: Alzheimer’s disease (AD) is an escalating global challenge, with more than 40 million people affected, and this number is projected to increase to more than 100 million by 2050. While amyloid-targeting antibody treatments (lecanemab and donanemab) are a significant step forward, the benefits of these therapies remain limited. This highlights the necessity for safe and effective compounds that offer greater therapeutic benefits to the majority of individuals with or at risk of AD. Drug repurposing allows for a cost-effective, time-efficient strategy to accelerate the availability of treatments, owing to the availability of safety information. Method: This study focuses on the third iteration of the Delphi consensus programme aimed at identifying new high-priority drug candidates for repurposing in AD. An international expert panel comprising academics, clinicians and industry representatives was convened. Through a combination of anonymized drug nominations, systemic evidence reviews, iterative consensus rankings, and lay advisory inputs, drug candidates were evaluated and ranked based on rational, non-clinical, and clinical evidence and overall safety profiles. Results: Among the 80 candidates that were nominated by the expert panel, seven underwent review, with only three candidates meeting the following consensus criteria of relevant mechanisms for targeting neurodegenerative pathways, non-clinical efficacy, and tolerability in older individuals. The three agents were: [1] the live attenuated herpes zoster (HZ) vaccine (Zostavax) [2], sildenafil, a phosphodiesterase-5 (PDE-5) inhibitor, and [3] riluzole, a glutamate antagonist. The HZ vaccine additionally offers potential for population-level dementia risk reduction. Conclusion: This Delphi consensus identified three high-priority drug repurposing candidates for AD with favourable safety profiles and mechanistic plausibility, which are considered suitable for pragmatic clinical trials, including remote or hybrid designs. The PROTECT platform, which supports international cohorts in the UK, Norway, and Canada, offers a well-established means to conduct such trials effectively, thus helping to accelerate the evaluation and potential deployment of these drug candidates to benefit individuals with or at risk for AD.
KW - Alzheimer’s
KW - Consensus
KW - Delphi
KW - Repurposing
KW - Treatment
UR - https://www.scopus.com/pages/publications/105022108430
U2 - 10.1186/s13195-025-01895-4
DO - 10.1186/s13195-025-01895-4
M3 - Review article
C2 - 41250235
AN - SCOPUS:105022108430
SN - 1758-9193
VL - 17
JO - Alzheimer's Research and Therapy
JF - Alzheimer's Research and Therapy
IS - 1
M1 - 237
ER -