Potency enhancers also work in the brain: The Viagra active ingredient Sildenafil could reduce the risk of Alzheimer’s dementia – by around 69 percent, as the evaluation of the health data of seven million people suggests. The Alzheimer’s risk decreased in the participants regardless of previous illnesses and other risk factors, as the researchers report in the journal “Nature Aging”. Supplementary laboratory tests also provided initial indications of the possible mechanism of action.
Actually, Sildenafil, the active ingredient in Viagra, is supposed to help against impotence and pulmonary hypertension. This works because the agent inhibits a specific enzyme called phosphodiesterase-5 (PDE-5), which causes the blood vessels to widen. At the same time, this enzyme inhibition has other effects, including Fat cells, the heart muscle and also Skin cancer cells can influence.
Keeping an eye on protein interactions
Now a team led by Jiansong Fang from the Lerner Research Institute at the Cleveland Clinic could have uncovered another effect of sildenafil. For their study, they examined 1,600 drugs that had already been approved to determine whether they might be effective against Alzheimer’s disease. To do this, they first created a molecular genetic model that depicts the various protein interactions in Alzheimer’s disease.
“The latest studies show that the interplay between amyloid and tau proteins is more likely to contribute to Alzheimer’s disease than both proteins taken by themselves,” explains Fang’s colleague Feixiong Cheng. “That is why we have postulated that active ingredients that attach to the molecular network between these two proteins must have the greatest potential for success.” disappointed.
With the help of the molecular genetic model, the scientists then scoured 1,600 active substances to see whether they could possibly have an effect.
Fewer Alzheimer’s cases when taking sildenafil
Among the 66 most promising candidates, one stood out: “Sildenafil presented itself as the best candidate for a possible effect against Alzheimer’s,” reports Cheng. To investigate this, the team analyzed the health data of seven million patients with health insurance in the United States. They compared how many of them had developed Alzheimer’s after six years and whether and how this proportion differed in the patients with a sildenafil prescription.
The result was surprisingly clear: “Compared to participants without sildenafil, taking sildenafil was significantly linked to a 69 percent lower risk of Alzheimer’s disease,” report Fang and his colleagues. Compared to patients who took four other active ingredients with possible dementia-preventive effects during this time, the risk was also reduced by 55 to 65 percent.
The relationship also remained significant when other risk factors such as high blood pressure, diabetes or arteriosclerosis were included.
Also effective in cell culture
“Taken together, these results suggest that sildenafil could be an active ingredient candidate for the prevention or treatment of Alzheimer’s,” the researchers state. They attribute this to the fact that the PDE-5 enzyme, which is inhibited by sildenafil, is also found in the brain. Initial experiments with mice had also shown that the active ingredient can inhibit the activity of two other proteins, which in turn promote the formation of malformed tau proteins.
To check this, Fang and his team cultivated brain cells from Alzheimer’s patients in the laboratory and treated them with sildenafil. The result: Under the influence of the sexual enhancer, the growth of neuronal processes was increased, and less tau protein fibers accumulated in the cell cultures. “This supports the potential of sildenafil against Alzheimer’s disease and also with regard to the mechanism,” said the researchers.
Clinical study is already being planned
However, Fang and his colleagues also emphasize that these are only preliminary, initial starting points. In order to prove a clear causal relationship and also the extent of the effect, systematic clinical studies must now follow. “We are already planning a phase II study with Alzheimer’s patients to confirm the causality and clinical effect of sildenafil,” says Cheng. (Nature Aging, 20231; doi: 10.1038 / s43587-021-00138-z)
Source: Cleveland Clinic