Old Drugs, New Possibilities: Rethinking Treatment for Alzheimer's and Related Dementias

Drug repurposing starts with medicines that already have a track record in humans, then asks whether they can help prevent, slow, or manage Alzheimer's disease and related dementias.

The development of a treatment for Alzheimer's disease and related dementias (ADRD) is commonly imagined as a process that begins from scratch: scientists identify a new biological target, create a new drug, test it, and eventually determine whether it is safe and effective. Part of the answer, however, may already be sitting in the medicine cabinet.

That is the premise behind drug repurposing: investigating medications originally developed or approved for one condition to determine whether they could also help prevent, slow, or manage another. For ADRD, this approach represents an important opportunity to rethink how the search for treatments is conducted.

Why repurpose existing drugs

Developing an entirely new medication is a lengthy, expensive, and uncertain process. Repurposed drugs offer researchers a potential head start because many have already been studied in humans through clinical trials, and the resulting data is widely available. Scientists may already understand important information about a drug's safety, dosing, side effects, and how it behaves in the body. The field has taken notice: a 2020 analysis of the Alzheimer's drug development pipeline counted 58 repurposed drugs across 53 ongoing clinical trials [1].

The National Institute on Aging (NIA), for example, has supported research examining existing medications as potential Alzheimer's treatments, including the anti-seizure medication levetiracetam [2] and the diuretic bumetanide [3]. That does not mean an existing drug can simply be prescribed for dementia because researchers discover a promising connection. Repurposed candidates still require rigorous testing to determine whether they are safe and effective for a new purpose. Starting with an existing body of knowledge, however, can potentially make the path from scientific idea to clinical investigation more efficient.

Finding new uses for familiar medicines

Today's drug repurposing research goes far beyond scientists simply noticing that a medication appears to have an unexpected benefit. Researchers can use large databases, electronic health records, genetic information, biological data, computational modeling, and increasingly sophisticated artificial intelligence tools to identify connections between existing drugs and the biological processes involved in ADRD.

Scientists might, for example, examine whether people taking a medication for another condition experience different rates of cognitive decline. Researchers can also study whether a drug affects inflammation, metabolism, vascular health, neuronal activity, or other pathways that may contribute to dementia. Modern computational and "omics" approaches, including genomics, transcriptomics, and proteomics, make it possible to screen enormous amounts of biological information and identify promising candidates that might otherwise have been overlooked.

ADRD is not a one-pathway problem

This approach may be especially valuable because Alzheimer's disease and related dementias are extraordinarily complex. Rather than being driven by one biological process, ADRD can involve interconnected changes related to amyloid and tau proteins, inflammation, vascular health, metabolism, genetics, neuronal function, and aging.

That complexity is one reason researchers are increasingly interested in precision approaches to drug repurposing. A medication may not benefit every person with ADRD equally. Certain therapies might ultimately prove more useful for specific patient populations based on genetics, biomarkers, disease stage, or other characteristics. The future of ADRD treatment, in other words, may not be about finding one drug for everyone. It may involve identifying the right intervention, or combination of interventions, for the right patient at the right time.

What this could mean for patients and families

For the millions of individuals and families affected by ADRD, time matters. Drug repurposing could expand the number of therapeutic possibilities researchers can investigate while making use of decades of existing medical knowledge. If successful, it could complement, not replace, the development of entirely new therapies.

It could also broaden the way ADRD management is understood. Instead of focusing on a single disease mechanism, researchers can investigate medications that influence several systems connected to brain health and determine which approaches may benefit particular groups of patients.

The challenges ahead

Substantial challenges remain. Promising findings from laboratory studies, databases, or observational health records do not automatically translate into successful treatments. Repurposed drugs need appropriately designed clinical trials, and researchers must determine which patients should receive them, at what dose, during what stage of disease, and for how long. Those challenges are also opportunities for innovation.

Turning existing knowledge into new hope

Integrated Senior Foundation and Insight Living hold that innovation in aging should ultimately lead back to a single question: how to improve the lives of older adults and the people who care for them.

ADRD affects far more than memory. It affects independence, medication management, family relationships, caregiving, safety, and quality of life. That makes progress in ADRD research deeply relevant to the entire senior living ecosystem, and it is why ISF is pursuing this work directly through a pending NIH R01 application with Cedars-Sinai focused on accelerating the discovery of repurposed therapies for ADRD.

Drug repurposing embodies an idea that is both simple and powerful: innovation does not always require starting over. Sometimes progress comes from taking what is already known, looking at it differently, and asking a new question. For ADRD researchers, that question is increasingly whether a medicine already in hand could become part of a treatment the field still urgently needs.