Drug repurposing for Alzheimer's disease: a Delphi consensus and stakeholder consultation

Area of Science:

• Neuroscience
• Pharmacology
• Gerontology

Background:

• Alzheimer's disease (AD) affects over 40 million globally, projected to exceed 100 million by 2050.
• Current amyloid-targeting antibody treatments offer limited benefits, necessitating novel therapeutic strategies.
• Drug repurposing presents a cost-effective and time-efficient approach to accelerate AD treatment development.

Purpose of the Study:

• To identify high-priority drug candidates for Alzheimer's disease (AD) repurposing.
• To evaluate potential treatments based on mechanistic rationale, efficacy, and safety.
• To inform the development of new therapeutic options for individuals with or at risk of AD.

Main Methods:

• Utilized the third Delphi consensus program with an international expert panel.
• Conducted systematic evidence reviews and iterative consensus rankings of nominated drug candidates.
• Evaluated drugs based on neurodegenerative pathway targeting, non-clinical efficacy, and tolerability in older adults.

Main Results:

• Identified three high-priority drug repurposing candidates for AD from 80 nominations.
• The selected agents include the herpes zoster (HZ) vaccine, sildenafil (a PDE-5 inhibitor), and riluzole (a glutamate antagonist).
• The HZ vaccine demonstrated potential for population-level dementia risk reduction.

Conclusions:

• Three drug candidates with favorable safety profiles and mechanistic plausibility were identified for AD repurposing.
• These candidates are suitable for pragmatic clinical trials, including remote or hybrid designs.
• The PROTECT platform can facilitate efficient evaluation and deployment of these potential AD treatments.