Cancer drugs with high repositioning potential for Alzheimer’s disease

ABSTRACT

Introduction

Despite the recent full FDA approval of lecanemab, there is currently no disease modifying therapy (DMT) that can efficiently slow down the progression of Alzheimer’s disease (AD) in the general population. This statement emphasizes the need to identify novel DMTs in the shortest time possible to prevent a global epidemic of AD cases as the world population experiences an increase in lifespan.

Areas covered

Here, we review several classes of anti-cancer drugs that have been or are being investigated in Phase II/III clinical trials for AD, including immunomodulatory drugs, RXR agonists, sex hormone therapies, tyrosine kinase inhibitors, and monoclonal antibodies.

Expert opinion

Given the overall course of brain pathologies during the progression of AD, we express a great enthusiasm for the repositioning of anti-cancer drugs as possible AD DMTs. We anticipate an increasing number of combinatorial therapy strategies to tackle AD symptoms and their underlying pathologies. However, we strongly encourage improvements in clinical trial study designs to better assess target engagement and possible efficacy over sufficient periods of drug exposure.

KEYWORDS:

• Alzheimer’s disease
• Cancer therapies
• hormone therapy
• Immunomodulators
• monoclonal antibody therapy
• retinoid X receptors
• targeted therapy
• tyrosine kinase inhibitors

Article highlights

• Currently, there is no disease modifying therapy to stop the progresssion of Alzheimer’s disease.

• The repurposing of anti-cancer drugs could accelerate the finding of disease modifying therapies for Alzheimer’s.

• One issue for anti-cancer drug repurposing for Alzheimer’s is the crossing of the blood-brain-barrie.

• A second issue or anti-cancer drug repurposing is the development of toxicities in frail Alzheimer’s patients.

• It is necessary to improve study design in animal and humams trials to improve clinical knowledge.

Declaration of interest

S Bacus discloses ownership interest in Seq Biomarque. B Decourt is a paid consultant for Lighthouse Pharmaceuticals and consultant for Seq Biomarque. M Sabbagh discloses ownership interest (stock or stock options) in NeuroTau, Inc., Optimal Cognitive Health Company, uMETHOD, Athira Pharma, Inc., Lighthouse Pharmaceuticals, Quince/Cortexyme, Seq Biomarque and EIP Pharma; consulting for Alzheon, Inc., Genentech (Roche Group), Acadia Pharmaceuticals, Inc., T3D Therapeutics, Inc., Novo Nordisk, Eisai Co., Ltd., Eli Lilly and Co., and KeifeRx.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was supported by grants from the National Institutes of Health (NIH): NIH R01AG059008, NIH P30AG072980, NIH R01AG073212, NIH R01CA232591, NIH R01AG071859 and NIH R01AG073826.