Fluoxetine, the common antidepressant known as Prozac, may be effective against atrophic (or dry) age-related macular degeneration (AMD).
Researchers from the University of Virginia School of Medicine (UVA) reported that the drug showed promise in the scientists’ lab tests and animal models.
The researchers believe fluoxetine works against AMD by binding with a particular agent of the immune system known as an inflammasome. Inflammasome, NLRP3-ASC, triggers the breakdown of the pigmented layer of the eye’s retina.
After conducting extensive bench research, Bradley Gelfand and his team at UVA’s Centre for Advanced Vision Science, tested fluoxetine and eight other depression drugs in lab mice to see what effect, if any, the drugs would have in a model of AMD. They found that fluoxetine slowed the progression of the disease, while the others did not.
They bolstered their results by examining two insurance databases encompassing more than 100 million Americans, with analysis concluding that patients taking fluoxetine for depression had a “significantly” slower rate of developing dry AMD.
Based on their findings, the researchers are urging clinical trials to test the drug in patients with AMD.
“Traditional approaches to drug development can be expensive and timeconsuming. On average, a new FDAapproved drug takes 10 to 12 years and costs US$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 diseaserelevant model, could greatly accelerate and reduce the cost of drug development.”
“These findings are an exciting example of the promise of drug repurposing – using existing medicines in new and unexpected ways,” said Mr Gelfand. “Ultimately, the best way to test whether fluoxetine benefits macular degeneration is to run a prospective clinical trial.”
If successful, they believe fluoxetine could be administered either orally or via a long-lasting implant in the eye.
Identification of fluoxetine as a direct NLRP3 inhibitor to treat atrophic macular degeneration. Meenakshi Ambati, Ivana Apicella, Shao-bin Wang, Siddharth Narendran, Hannah Leung, Felipe Pereira, Yosuke Nagasaka, Peirong Huang, Akhil Varshney, Kirstie L. Baker, Kenneth M. Marion, Mehrdad Shadmehr, Cliff I. Stains, Brian C. Werner, Srinivas R. Sadda, Ethan W. Taylor, S. Scott Sutton, Joseph Magagnoli, Bradley D. Gelfand. Proceedings of the National Academy of Sciences Oct 2021, 118 (41) e2102975118; DOI: 10.1073/pnas.2102975118