An FDA-approved drug used to treat erectile dysfunction may soon be recommended as a therapy to reduce the risk of Alzheimer's disease.
Analyzing health insurance data as well as laboratory research into the genetic and neurological effects of sildenafil - a drug commonly sold under the brand name Viagra - US researchers have confirmed the drug's potential to prevent critical proteins in nerve cells from becoming tangled in a deadly mess. reported Science alert.
Studies have repeatedly shown that enzyme blockers called phosphodiesterase (PDE) inhibitors not only have the ability to promote blood flow to the penis, but can also prevent the neurodegeneration responsible for dementia.
This potential may not be so surprising given that PDEs are known to be involved in neural signaling pathways that influence neuroplasticity. Previous research in animal models has shown that the PDE inhibitor sildenafil reduces the excessive phosphorylation of tau proteins in nerve cells, which causes them to form toxic tangles, thereby helping to improve cognitive health and memory.
Still, not all studies have been so flattering, with some showing no population-level effect at all. And while drugs can have an effect at a neurological level, the mechanisms behind this process are still not fully understood.
US researchers are using cell cultures of neurons created from stem cells donated by Alzheimer's patients to map the metabolic and genetic activity that underlies the therapeutic effect of sildenafil.
After five days of treatment, lab-grown neurons produced significantly lower levels of tau proteins when excessive concentrations of phosphorus were added, confirming sildenafil's ability to protect brain cells.
Reading the messages produced by cells' DNA reveals hundreds of changes in gene expression, many of which are related to inflammation, the breakdown of communication between nerves, and the targeting of nerve cell structures.
While further research will be needed to determine exactly how these subtle influences may be involved in the pathology behind Alzheimer's disease, understanding the major gene families affected by sildenafil has provided a solid foundation for understanding its action and perhaps why some brains develop Alzheimer's disease in the first place.
The second part of the study used artificial intelligence to look for signs of sildenafil's effect at the population level. Previous studies have used Medicare data to find that sildenafil can reduce the risk of Alzheimer's disease by about 60%.
However, they are based on only one insurance database, and it is possible to miss variables that could lead to a different conclusion. What's more, these studies show that patients treated for high blood pressure in the lungs, or pulmonary hypertension (PH), do not experience the same reduction in dementia risk.
The researchers included four treatments commonly prescribed for BH in their analysis of the data, not only confirming that sildenafil reduced the risk of Alzheimer's by about 60%, but that it did reduce the risk in people with pulmonary hypertension.
"After integrating this large amount of data using computations, it is gratifying to see the effect of sildenafil in human neurons and real results for patients," said biomedical informatics scientist at Cleveland Clinic and co-author of the first paper Feishong Cheng.
"We believe our findings provide the necessary evidence for clinical trials to further investigate the potential effectiveness of sildenafil in Alzheimer's patients," he added.
Now that sildenafil has received ACHL approval for erectile dysfunction, proving its safety and effectiveness in reducing the risk of Alzheimer's disease could provide health authorities with a quick means of dealing with what appears to be a rising tide of dementia.
The world's aging population can expect the number of people with dementia to 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 that can reduce this number, such research will be essential to prove its value./BGNES
