How generic Viagra can treat Alzheimer’s disease

We all know that sildenafil—a component in the generic version of Viagra—can help treat erectile dysfunction. Over the last few years, research has suggested that the same drug also can be repurposed as a potential treatment for Alzheimer’s disease.

A recent study in the Journal of Alzheimer’s Disease supported earlier publications on the potential benefits of sildenafil, which is a type of drug called a phosphodiesterase type-5 inhibitor. Dr.  Feixiong Cheng, director of the Cleveland Clinic Genome Center, led this research, and said his team used artificial intelligence to integrate data from computational models, insurance claims data, and observations from brain cells in Alzheimer’s patients.

The work was co-authored by Dr. Jeffrey Cummings, research professor in the department of brain health at the University of Nevada, Las Vegas and director of the Chambers-Grundy Center for Transformative Neuroscience at UNLV.

The study extends and amplifies a study published in Nature Aging in 2021; that work analyzed computational models to identify sildenafil as a promising treatment for Alzheimer’s.

That research indicated a 69 percent lower risk of Alzheimer’s among generic Viagra users.

To be clear: These studies represent early steps in examining the potential effectiveness of sildenafil in patients with Alzheimer’s disease. In a press release about the new research, Dr. Cheng said he believes the findings provide evidence needed for further clinical trials.

“After integrating this large amount of data computationally, it is rewarding to see sildenafil’s effects in human neurons and real-world patient outcomes,” he said.

As part of this recent study, Dr. Cheng and his team analyzed millions of de-identified insurance claims, which revealed a 30-54 percent reduction in Alzheimer’s disease diagnoses among patients who took sildenafil compared to those who did not. Additionally, in brain cells from Alzheimer’s patients, researchers showed that sildenafil lowers levels of neurotoxic tau proteins, which are known to be associated with Alzheimer’s disease when they build up.

Dr. Cheng’s team also found that neurons treated with sildenafil expressed genes related to cell growth, improved brain function, reduced inflammation and other processes known to protect against the neural degeneration associated with Alzheimer’s disease.

Other recent studies had different results.

One, published in Neurology last month, showed the effect of sildenafil on Alzheimer’s symptoms was not as large.

The authors of the Neurology paper found that men prescribed erectile dysfunction drugs were only 18 percent less likely to develop Alzheimer’s disease years later.

This study included 269,725 men who were diagnosed with erectile dysfunction and who did not have any memory or thinking problems at the start of the study. Just over half (55%) of these were taking phosphodiesterase type-5 inhibitor drugs, including sildenafil (sold as Viagra), tadalafil (Cialis), vardenafil and avanafil, and were compared to those with erectile dysfunction but not prescribed the drugs.

What’s was especially interesting about the Neurology study is that the men who took the drug regularly had greater benefits, but the results in real terms were 8.1 cases per 10,000 vs. 9.7 cases per 10,000.

This data suggests that while sildenafil-type drugs may help treat Alzheimer’s symptoms, the drug certainly is not a cure. It also suggests there is no reason to believe that the effects would not also be relevant for other similar drugs such as Cialis.

Either way, sildenafil and other phosphodiesterase type-5 inhibitors certainly are becoming more prevalent in modern society.

These erectile dysfunction drugs are in a class of medications called vasodilators, which dilate or prevent constriction of the blood vessels, thereby allowing greater blood flow to various organs in the body.

They were initially developed to treat hypertension and angina. They act on a cell-signaling messenger that has also been investigated for its links to memory. These drugs are also able to cross the blood-brain barrier and may affect brain cell activity. Animal research has found to have some neuroprotective benefits.

Currently, sildenafil is FDA-approved to treat both erectile dysfunction (again, in the form of of Viagra) and pulmonary hypertension (in the generic form of a drug named Revatio).

The push to uncover new drugs to treat Alzheimer’s disease marches on—the most recent paper on this subject indicated that on the index date of January 1, 2023, there were 187 trials assessing 141 unique treatments for Alzheimer’s disease.

Looking forward, researchers increasingly are investigating the extent to which other existing drugs could be used to mitigate the effects of Alzheimer’s and other types of neurodegenerative disease.

Dr. Mitzi Gonzales, a clinical neuropsychologist at Cedars-Sinai in Los Angeles, said this general strategy of attempting to repurpose knowledge from one field and apply it to Alzheimer’s is a promising way to uncover more targeted interventions.

“There’s been a lot of thought that this is a complex problem, and we don’t know how to solve it, [so] we need to try a lot of different [approaches],” she said. “We are going to fail, but we need to fail quickly and learn from those mistakes and then be able to take the lessons learned and be able to modify that trial a little bit more, or perhaps consider a different target or combination of therapies.”

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