An FDA-approved pharmaceutical used to treat erectile dysfunction could soon be recommended as a therapy for decreasing the risk of Alzheimer’s disease.
By analyzing medical insurance data alongside a laboratory investigation on the genetic and neurological effects of sildenafil – a drug sold commonly under the brand name Viagra – researchers in the US have validated the medication’s potential in keeping critical proteins in nerve cells from tangling into a deadly mess.
Studies have repeatedly demonstrated enzyme blockers called phosphodiesterase (PDE) inhibitors not only have an ability to promote blood flow in the penis, but could prevent the neurodegeneration responsible for dementia.
This potential might not be all that surprising, given PDEs are known to be involved in nerve signaling pathways that influence neuroplasticity. Previous investigations on animal models have shown the PDE inhibitor sildenafil reduces the excessive phosphorylation of ‘tau’ proteins in nerve cells that causes them to form toxic tangles, helping improve cognitive health and memory.
Yet not all research has been so flattering, with some studies failing to notice an effect on the population level at all. And while the drugs may have an effect on a neurological level, the mechanisms behind this process still aren’t fully understood.
Researchers in the US used cell cultures of neurons created from stem cells donated by Alzheimer’s patients to map the metabolic and genetic activity behind sildenafil’s therapeutic effects.
Following five days of treatment, the laboratory-grown neurons produced significantly lower levels of tau proteins with excess concentrations of phosphorus added, confirming sildenafil’s knack for protecting brain cells.
A reading of the messages produced by the cells’ DNA found hundreds of changes in the expression of genes, many involving the inflammation, breakdown in communication between nerves, and guidance of nerve cell structures.
While additional studies will be needed to pinpoint exactly how these subtle influences may be involved in the pathology behind Alzheimer’s, understanding the main gene families affected by sildenafil provided a solid foundation for understanding why it works and perhaps why some brains develop Alzheimer’s in the first place.
A second feature of the study used AI to look for signs of sildenafil working on a population level. Previous studies have used medical insurance data to find sildenafil can reduce the risk of Alzheimer’s disease by around 60 percent.
Yet these relied on just a single insurance database, potentially missing out on variables that might reveal a different conclusion. What’s more, these studies suggested patients being treated for high blood pressure in the lungs, or pulmonary hypertension (PH), didn’t see the same drop in dementia risk.
The researchers included four treatments commonly prescribed for PH in their data analysis, not only confirming sildenafil decreased Alzheimer’s risk by around 60 percent, but finding it reduced risk in people with pulmonary hypertension after all.
“After integrating this large amount of data computationally, it is rewarding to see sildenafil’s effects in human neurons and real-world patient outcomes,” says Cleveland Clinic biomedical informatician and co-first author Feixiong Cheng.
“We believe our findings provide the evidence needed for clinical trials to further examine the potential effectiveness of sildenafil in patients with Alzheimer’s disease.”
With sildenafil already given the FDA tick of approval for erectile dysfunction, demonstrating its safety and effectiveness in reducing Alzheimer’s risk could provide health authorities with a quick means of addressing what looks to be a rising tide of dementia.
Aging populations around the globe can expect the number of individuals living with dementia to nearly double every 20 years, from just under 80 million at the end of this decade to nearly 140 million by mid-century.
If we already have a pill at hand that can keep these numbers down, research like this will be vital in proving its worth.
This research was published in the Journal of Alzheimer’s Disease.
