An FDA-approved medicine used to treat erectile dysfunction may soon be suggested as a therapy to reduce the incidence of Alzheimer’s.
Researchers in the US validated the potential of sildenafil, a drug sold under the brand name Viagra, by analyzing medical insurance data and conducting a laboratory investigation on its genetic and neurological effects. The medication prevents critical proteins in nerve cells from tangling, which can be fatal.
Enzyme blockers, known as phosphodiesterase (PDE) inhibitors, have been shown to increase blood flow in the penis and maybe prevent neurodegeneration, which causes dementia.
Given PDEs’ involvement in nerve signaling pathways that regulate neuroplasticity, this possibility may not come as a surprise.Sildenafil, a PDE inhibitor, has been proven in animal studies to improve cognitive health and memory by reducing excessive phosphorylation of ‘tau’ proteins in nerve cells, which generates toxic tangles.
However, several investigations have found no influence on the population level. And, while the medications may have an influence on the neurological system, the processes underlying this process are still unknown.
Researchers in the US developed cell cultures of neurons from stem cells provided by Alzheimer’s patients to map the metabolic and genetic processes underlying sildenafil’s therapeutic effects.
Following five days of therapy, laboratory-grown neurons produced considerably lower quantities of tau proteins when extra phosphorus was introduced, indicating sildenafil’s ability to protect brain cells.
A reading of the messages created by the cell’s DNA revealed hundreds of alterations in gene expression, many of which included inflammation, a breakdown in nerve transmission, and nerve cell guidance.
While more research is needed to determine how these subtle influences may play a role in the pathology of Alzheimer’s, understanding the main gene families affected by sildenafil provided a solid foundation for understanding why it works and, possibly, why some brains develop Alzheimer’s at all.
The study’s second aspect used artificial intelligence to seek for indicators of sildenafil at the population level. Previous research using medical insurance data found that sildenafil can reduce the risk of Alzheimer’s disease by approximately 60%.
However, these were based on a single insurance database, which may have excluded characteristics that would have led to a different conclusion. Patients treated for pulmonary hypertension (PH) did not see the similar reduction in dementia risk, according to these studies.
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