An FDA-approved medication for treating enlarged prostate and high blood pressure, may also have potential to prevent or delay Alzheimer's disease, according to a new study by researchers at University of Iowa Health Care.
The connection may seem surprising, but the new study published in Alzheimer’s Research & Therapy builds on previous work by the UI team that has identified a potential protective effect of the drug terazosin in other neurodegenerative diseases, including Parkinson's disease and dementia with Lewy bodies.
The root of terazosin’s neuroprotective effect lies in the drug’s ability to boost energy production in brain cells by enhancing a process called glycolysis. UI researchers believe this ability of terazosin and related drugs to improve metabolic energetics might help protect against neurodegeneration in general. Subsequent studies have provided convergent evidence from US private insurance, Medicare, and the VA patient databases, as well as patient data from Canada and Denmark, supporting this idea for Parkinson’s disease and dementia with Lewy bodies.
The new study, led by Nandakumar Narayanan, MD, PhD, and Qiang (Johnson) Zhang, MD, examined terasozin’s effect on Alzheimer’s disease, a condition that affects over 6 million Americans and is the leading cause of dementia. The UI researchers used two experimental models of Alzheimer's disease; yeast cells and mice genetically altered to mimic aspects of Alzheimer's and also analyzed data from two patient database to look for benefits due to terazosin.
They found that terazosin boosted cellular energy levels in yeast cells and reduced clumping of amyloid protein, which is considered a hallmark of Alzheimer’s disease. In the mouse model, terazosin also reduced amyloid abnormalities in the brain and improved certain memory and cognitive problems in the mice. In one database of participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI), the researchers found that Alzheimer's patients taking terazosin or other glycolysis-enhancing drugs had slower progression of cognitive problems and improvement in a biomarker measuring energy metabolism. These findings were also mirrored in a second large patient database, which showed that patients taking a glycolysis enhancing drug had lower risks of developing Alzheimer's disease.
“Our study provides preliminary evidence that glycolysis-enhancing drugs, like terazosin, have therapeutic potential in Alzheimer’s disease,” says Zhang, UI clinical assistant professor of neurology and lead author of the study. “Because this is a fundamental mechanism, our work could be instrumental in inspiring novel disease-modifying therapies for Alzheimer’s disease and related diseases.”
Zhang notes that although the findings suggest that terazosin is highly promising as a novel therapy in Alzheimer’s disease, prospective randomized double-blind placebo controlled clinical trials are still needed to prove its efficacy in Alzheimer’s disease.
The researchers’ intention to pursue clinical trials of terazosin for Alzheimer’s and other neurodegenerative diseases is aided by the fact that the drug already has a known safety record and long use in patients, which significantly reduces the barriers for initiating clinical testing.
“We are excited about rigorously testing the potential of metabolic energetics as a target for neurodegenerative disease, as this could transform current approaches to diagnosis and care for these devastating diseases,” says senior study author Narayanan, UI professor of neurology and associate director of the Iowa Neuroscience Institute.
In addition to Zhang and Narayanan, the team included UI researchers in neurology, psychiatry, internal medicine, pathology, and biology, and colleagues from Duke University and Johns Hopkins University.
The work was supported in part by grants from the National Institute of Neurological Disorders and Stroke and the National Institute on Aging, both part of the National Institutes of Health, and the Cannon-Williams Faculty Fellowship at University of Iowa and the Athens Neurodegeneration Fund.