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UVa study links Prozac use with fending off age-related blindness

Prozac may not only help fight depression; it also could help you keep your eyesight.

A University of Virginia Medical School review of insurance databases containing records from more than 100 million Americans shows that fluoxetine, best known as Prozac, may offer a first-line treatment for atrophic, age-related macular degeneration, also known as dry macular degeneration.

The condition, referred to by researchers as AMD, affects nearly 200 million people worldwide and is a leading cause of blindness in people older than 50.

The drug has shown promise in the scientists’ lab tests and animal models and the database review adds to the promise, said UVa’s Bradley D. Gelfand.

“These findings are an exciting example of the promise of drug repurposing, using existing medicines in new and unexpected ways,” said Gelfand, of UVA’s Center for Advanced Vision Science. “Ultimately, the best way to test whether fluoxetine benefits macular degeneration is to run a prospective clinical trial.”

Gelfand said the research team was led in its efforts by Albemarle County High School student Meenakshi Ambati, who has worked on the research during summers and after-school hours.

Ambati won a $50,000 Davidson Institute Fellowship and scholarship for her research discovery to treat a common disease that causes blindness.

As a volunteer in Gelfand’s laboratory, she initially employed bench laboratory techniques. When the pandemic all but shut down normal laboratory operations, she was switched analyzing the databases, giving the study its multi-pronged approach.

“The project really started with her. She was interested in looking at existing drugs that could be repurposed because this disease currently has no FDA approved therapies,” Gelfand said. “When she looked at some experimental compounds that are many years, and very likely many millions of dollars, away from actually becoming drugs, she noticed there was one with a similar structure to fluoxetine.”

“I think vision is our most special sense and when I learned that millions of people are at risk of going blind from dry macular degeneration, I wanted to contribute to the search for a treatment,” Ambati said. “Hundreds of clinical trials for this disease have failed, so I wanted to take a completely different approach, by repurposing a drug that’s already [Food and Drug Administration-approved] for another disease.”

Ambati said she settled on Prozac because she found it could block certain inflammatory pathways responsible for dry macular degeneration.

“I was astonished to find that people who took Prozac for depression were almost 20% less likely to get dry macular degeneration than patients who didn’t,” she said. “This combination of biology and data science enabled us to make a strong case for testing Prozac in a prospective, randomized clinical trial for this disease.”

The researchers believe fluoxetine fights AMD by binding with inflammasomes, which are created by the body’s immune system.

Inflammasomes are a normal part of a healthy human body and serve as part of the body’s defense system against bacteria and other invaders. Problems begin, however, when the body’s natural control mechanisms don’t tamp down the inflammasomes and the molecules run amok.

The particular inflammasome – and there are many – is NLRP3-ASC, which triggers a breakdown of the pigmented layer of the eye’s retina.

Gelfand and his team tested fluoxetine and eight other depression drugs in lab mice to see if any of the drugs worked. Fluoxetine slowed the disease’s progression while the others did not.

That’s when Ambati stepped in.

“Because so many people take this drug, she was able to look in large databases of health information and found that among people with depression, the people who were taking Prozac were at a reduced risk of developing a new diagnosis of AMD by something like 15%,” Gelfand said.

Although 15% is not a large number, because there are so many people at risk of AMD, the possible treatment could help millions.

“It’s not like penicillin for pneumonia, but when we’re talking about many millions of people at risk and suffering from this disease, it equates to a large number of people who could benefit,” he said.

The next step in the process would be to run a clinical trial. Based on the findings, the researchers believe that if the drug proves successful, it could be administered either orally or through an ocular implant.

But Gelfand said there are some hurdles to run, the first of which is funding. Most research funded by pharmaceutical companies is based on new drugs that may be patented rather than existing drugs. That can cost as much as $2.8 billion and take a decade or more.

The other hurdle would be the clinical trial’s expansive scope.

“The study we would want to do would be a preventive one so you’d need to pick many, many people for the study before you had enough that develop or do not develop AMD so you could say for sure if your drug worked,” Gelfand said. “We’d love to do a clinical trial and that is the goal, but it’s going to take a while.”

In the meantime, Gelfand said people should neither start taking fluoxetine to stave off AMD or change their prescriptions to thwart the condition.

“Based on this research, no one should be going out and either switching to fluoxetine or start taking it. These are serious drugs and people should consult with their physician before considering anything,” he said.

“We’re in the early stages of a very long game,” Gelfand said. “It’s a very long slog and a long process, but every process begins with the first step.”

Although there is a long way to go, Gelfand said the idea of finding existing drugs to treat conditions is time and money efficient. He was involved earlier this year in a similar study that determined anti-HIV drugs may also be useful against dry macular degeneration.

“We are only scratching the surface of finding new uses for old drugs,” Gelfand said. “It’s tempting to think about all the untapped therapeutic potential of medicines sitting on pharmacy shelves.”


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