An international consortium of leading researchers has identified three established pharmaceutical agents, currently prescribed for distinct medical conditions, that exhibit considerable promise in either preventing the onset of Alzheimer’s disease or serving as therapeutic interventions for those already diagnosed. This innovative approach bypasses the lengthy and prohibitively expensive process of de novo drug discovery, instead focusing on the reevaluation of existing, approved medications for potential secondary applications in neurodegenerative disorders. The groundbreaking study, a collaborative effort primarily funded by the Alzheimer’s Society and spearheaded by academic institutions including the University of Exeter, has been formally documented and disseminated through the esteemed journal Alzheimer’s Research and Therapy.
The meticulous review process, which involved an expert panel comprising 21 distinguished dementia specialists drawn from academic, clinical, and pharmaceutical sectors, alongside individuals with lived experience of dementia, critically assessed a pool of 80 previously authorized medications. The primary objective was to discern which of these existing treatments possessed the most compelling biological rationale and empirical evidence to warrant further investigation for their impact on Alzheimer’s disease, a condition that represents over half of all dementia diagnoses globally. These specialists, working through multiple iterative evaluation stages, ultimately converged on a select group of three compounds deemed "priority candidates" for subsequent, more rigorous clinical exploration. The selection criteria were multifaceted, emphasizing not only the drugs’ capacity to engage with biological pathways implicated in the pathogenesis of Alzheimer’s but also their demonstrated efficacy in preclinical models, such as cell cultures and animal studies, and crucially, their established safety profile for administration in older adult populations.
Among the trio of promising agents, a vaccine formulated to combat herpes zoster, commonly known as shingles, distinguished itself with particularly compelling data. This vaccine, requiring a minimal dosing regimen of no more than two administrations and boasting a long-standing track record of safety and tolerability, has garnered attention due to prior epidemiological observations. These studies have suggested a notable correlation, indicating that individuals who received the shingles vaccine were approximately 16% less likely to subsequently develop dementia. The research team is now actively advocating for the initiation of large-scale clinical trials within the United Kingdom to definitively ascertain the protective or therapeutic benefits of this vaccine in individuals affected by Alzheimer’s or those at elevated risk. These proposed trials are envisioned to leverage the capabilities of the PROTECT initiative, an established online platform designed to facilitate brain health research through annual participant questionnaires on health and lifestyle, as well as the collection of relevant health data.
Beyond the shingles vaccine, the compound sildenafil, widely recognized under the brand name Viagra for its efficacy in treating erectile dysfunction, also emerged as a candidate of significant interest. While its mechanism of action in the context of Alzheimer’s is still being elucidated, preliminary findings suggest it may play a role in improving cerebral blood flow or possessing neuroprotective qualities. Furthermore, riluzole, a medication currently employed in the management of amyotrophic lateral sclerosis (ALS), a form of motor neurone disease, presented another noteworthy contender. Its potential relevance to Alzheimer’s likely stems from its effects on neurotransmitter systems or its ability to modulate excitotoxicity, a process implicated in neuronal damage.
The strategic rationale behind prioritizing drug repurposing for Alzheimer’s research is rooted in the profound societal and economic burden imposed by dementia. In the United Kingdom alone, dementia stands as the leading cause of mortality, impacting an estimated one million individuals, with projections indicating that one in three people born today will face this diagnosis during their lifetime, and tragically, no definitive cure currently exists. The conventional pathway for pharmaceutical development, from initial discovery to market approval, is notoriously protracted, often spanning a decade to fifteen years, and demanding investments in the billions of pounds, all while offering no guarantee of success. Consequently, the exploration of existing, well-characterized medications offers a potentially more expedited, safer, and economically viable route to developing novel interventions for Alzheimer’s disease. This endeavor has also received crucial financial and logistical support from various influential bodies, including the National Institute for Health and Care Research (NIHR), the Exeter Biomedical Research Centre, and the NIHR HealthTech Research Centre focused on Brain Health.
While the three priority candidates have garnered the most attention, the expert panel also evaluated an additional five medications that, though showing some promise, did not meet the stringent criteria for designation as top contenders. These included fingolimod, primarily utilized in the treatment of multiple sclerosis; vortioxetine, an antidepressant; microlithium, also employed for depression; dasatinib, a targeted therapy for certain types of leukemia; and cytisine, a compound historically used in smoking cessation therapies and anesthetics. Their inclusion in the broader review underscores the comprehensive nature of the assessment and the systematic approach to identifying potential therapeutic leads.
Leading voices in the field emphasize the critical need for continued scientific rigor and further validation. Dr. Anne Corbett, a distinguished Professor of Dementia Research at the University of Exeter, articulated this sentiment, stating, "Conquering dementia necessitates exploring every avenue of scientific inquiry, from leveraging our existing knowledge base to uncovering entirely new therapeutic agents for both treatment and prevention." She further elaborated on the significance of drug repurposing, characterizing it as "an indispensable component of this multifaceted strategy, enabling us to transition existing medicines from their current applications to future treatments for neurodegenerative conditions." Professor Corbett underscored the paramount importance of further investigation, stressing that "it is imperative to highlight that these pharmaceutical agents require extensive scrutiny before we can definitively ascertain their utility in managing or averting Alzheimer’s disease. Robust clinical trials are now essential to fully comprehend their genuine therapeutic value and confirm their efficacy in this capacity."
Echoing this call for diligent research, Professor Fiona Carragher, Chief Policy and Research Officer at the Alzheimer’s Society, conveyed a message of optimism underpinned by scientific pursuit. "Dementia inflicts profound devastation upon lives, yet our conviction remains strong that scientific research holds the key to overcoming it," she affirmed. Professor Carragher drew a historical parallel, recalling the successful repurposing of aspirin from a simple pain reliever to a medication that significantly reduces the risk of cardiovascular events like heart attacks and strokes. "This," she concluded, "is precisely the kind of transformative progress we aspire to witness in the realm of dementia, and it underscores why we consider drug repurposing to be one of the most exhilarating and promising frontiers in dementia research today."
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