The antidepressant fluoxetine, best known as Prozac, could offer the first treatment for the leading cause of blindness among people over 50, new research from the University of Virginia School of Medicine suggests.
Researchers have found early evidence that the drug fluoxetine may be effective against atrophic (or ‘dry’) age-related macular degeneration, a condition that affects nearly 200 million people worldwide. An analysis based on bench research, mouse models and huge insurance databases concluded that patients taking fluoxetine were less likely to develop atrophic macular degeneration (AMD).
On the strength of their findings, which were published in PNAS, the researchers are urging the investigation of fluoxetine to treat AMD, possibly as an oral pill or slow-release implant in the eye.
“These findings are an exciting example of the promise of drug repurposing, using existing medicines in new and unexpected ways,” said Bradley D. Gelfand, PhD, 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.”
The researchers believe fluoxetine works by binding with an inflammasome, NLRP3-ASC, which triggers the breakdown of the pigmented layer of the eye’s retina.
After conducting extensive bench research, Dr Gelfand and his team tested fluoxetine and eight other depression drugs in lab mice. Fluoxetine slowed the progression of the disease, but the others did not, the scientists found.
Encouraged by their findings, the researchers looked at fluoxetine use among patients aged over 50 in two enormous insurance databases with over 100 million records. They found that people taking the drug had a “significantly” slower rate of developing dry AMD.
Their approach, which combines bench research with big-data analysis, could lead to faster repurposing of existing drugs.
“Traditional approaches to drug development can be expensive and time-consuming: On average, a new FDA-approved drug takes 10–12 years and costs $2.8 billion (present-day dollars) to develop,” the researchers wrote. “Our identification of the unrecognised therapeutic activity of an existing FDA-approved drug using big data mining, coupled with demonstrating its efficacy in a disease-relevant model, could greatly accelerate and reduce the cost of drug development.”
Dr Gelfand was involved earlier this year in using a similar approach to determine that HIV drugs known as nucleoside reverse transcriptase inhibitors, or NRTIs, may be useful against dry macular degeneration as well.
“While we have had a great deal of success with the approach of using real-world patient data, we may have only begun to scratch the surface of finding new uses for old drugs,” said Dr Gelfand, of UVA’s departments of ophthalmology and biomedical engineering. “It is tempting to think about all the untapped therapeutic potential of medicines sitting on pharmacy shelves.”
Source: University of Virginia
