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As scientific knowledge of Alzheimer’s and related dementias has grown, drug development projects have evolved to reflect this complexity. Like cancer and its many subtypes, the many types of dementias will likely require targeted treatments aimed at an individual’s unique disease characteristics.
While FDA’s June 2021 accelerated approval of aducanumab is a milestone in Alzheimer’s research, an array of treatments will be necessary to successfully halt or reverse the effects of these diseases for everyone. A precision medicine approach would deliver specific treatments based on a person’s type of dementia as diagnosed through lab and imaging tests.
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As knowledge advances, scientists are developing more precise treatments and preventions aimed at specific types of Alzheimer’s and related dementias. Today, many kinds of compounds are chosen for testing and development as drug candidates.
In addition to drugs aimed at a specific disease pathway, NIH-funded researchers are also exploring many variations of targets simultaneously, considering combinations of treatments, and working to repurpose existing drugs to treat these diseases.
New drug development projects in the lab
NIA recently funded several new projects (see table) through its Alzheimer’s Drug Development Program . Each project is focused on developing a new drug that targets a different biological process, such as brain inflammation, known to go awry during the development of Alzheimer’s and related dementias. If successful, these NIH-supported preclinical drug development studies will result in new candidate drugs that could then be tested in people.
Drugs in clinical trials
As a result of the substantial research progress achieved over the last several years in understanding how Alzheimer’s and related dementias develop and worsen, the drug development pipeline has never been more diverse.
Drug candidates now in clinical studies target multiple aspects of the disease process. Thanks to increased investments in Alzheimer’s and related dementias research, NIH-funded clinical studies extend beyond drug candidates that target amyloid plaques in the brain. The continuously updated list of NIA-Funded Active Alzheimer’s and Related Dementias Clinical Trials and Studies catalogs the many different disease pathways.
NIA is supporting many late-stage drug trials and early-stage drug trials for Alzheimer’s and related dementias. In addition, several studies are evaluating drug candidates for treating psychological or neurological symptoms of dementia, including apathy, agitation, and restless legs.
Drug candidates that are shown to be safe and effective in late-stage trials can then be presented to FDA. Before drugs are approved for use in people, FDA ensures that drugs work correctly and that their health benefits outweigh their known risks.
Program Spotlight: New uses for FDA-approved drugs
One way NIH works to find effective ways to treat dementia is by considering drugs that FDA has already deemed safe for people with other conditions. The thinking is that some of these drugs could be repurposed to effectively prevent or treat Alzheimer’s and related dementias as well.
As one example, NIA’s Clinical and Translational Neuroscience Section in the Laboratory of Behavioral Neuroscience scientists are leading the Drug Repurposing for Effective Alzheimer’s Medicines (DREAM) study. DREAM is an NIA collaboration with researchers at Harvard Medical School, Rutgers University, and Johns Hopkins University School of Medicine to repurpose FDA-approved drugs for dementia .
The research team recently reported that they discovered a network of about 20 biological pathways linked to abnormal brain metabolism in people with Alzheimer’s and related dementias. These abnormalities may precede or influence the brain changes that lead to dementia. Next, they identified 35 FDA-approved drugs that might be active against the network of 20 pathways. Of these 35, the team selected 15 drugs as the best candidates for further analysis.
From this point, the team can analyze data collected during routine health care for the effects of a candidate drug on the development of dementia. Data sources include electronic health records from U.S. Medicare and the United Kingdom. The analysis will estimate the incidence of dementia for people treated with the candidate drug and compare it to those receiving another drug for the same disease.
Results from the DREAM study will help guide future research. If a drug appears to reduce the risk or severity of Alzheimer’s or a related dementia, researchers could conduct lab tests to determine how the drug works against dementia, and the drugs could eventually be tested with people in clinical trials.
Research at other NIA-supported labs
NIA also funds drug repurposing research at its grantee institutions. Following are examples:
- A study published recently showed how electronic medical records from 1.7 million U.S. veterans can be used to identify FDA-approved drugs that may have potential for Alzheimer’s . First, the research team demonstrated that the risk of being diagnosed with Alzheimer’s was greater for veterans who have a history of traumatic brain injury than those without traumatic brain injury. Next, the researchers analyzed whether any of four classes of drugs had shown evidence of lowering the risk of Alzheimer’s. They found that veterans who took a combination of medicines that lower blood pressure and cholesterol were less likely to develop Alzheimer’s after traumatic brain injury. Although the analysis was promising, more studies are needed before this drug combination can be tested in people.
- A research team devised a system of ranking 80 compounds , including 33 FDA-approved drugs, according to their likelihood of being active against certain Alzheimer’s-related genetic mechanisms. The researchers relied on data collected by the NIH-funded Accelerating Medicines Partnership® for Alzheimer’s Disease (AMP AD). The team concluded that their system has the potential to predict which drugs can inhibit disease.
- To build on findings like those above, NIH released a funding initiative in 2020 called Translational Bioinformatics Approaches to Advance Drug Repositioning and Combination Therapy Development for Alzheimer’s Disease . The goal is to leverage the power of big data and open science in advancing drug repurposing and combination therapy development.