Fluoxetine as a Potential Treatment for Atrophic AMD

Article: Prozac Pegged as Potential Treatment for a Leading Cause of Blindness
Source: University of Virginia Medicine
Published: October 21, 2021

Fluoxetine prevents RPE cell death in a
mouse model of Alu RNA-induced AMD

Related to research by Jayakrishna Ambati, M.D., at University of Virginia, colleagues at the same institution are exploring drug repurposing in the treatment of eye diseases such as atrophic age-related macular degeneration (AMD), also known as geographic atrophy. In this case, the research team is examining the therapeutic potential of fluoxetine (Prozac), an FDA-approved medication for clinical depression. The investigators explain, “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. Our identification of the unrecognized 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.” In particular, they tested fluoxetine and eight other antidepressant drugs in mouse models of Alu RNA-induced AMD, and note that fluoxetine, but not the other antidepressants, was effective at slowing the progression of the disease. They report that fluoxetine acts as a direct inhibitor of the inflammasome (components NLRP and ASC from assembling) in silico, in vitro, and in vivo to prevent the cytokine release that ultimately leads to retinal pigmented epithelium (RPE) and retinal degeneration. Next, the researchers applied big data mining to two large health insurance databases, together encompassing more than 100 million Americans, to determine any associations. The analysis showed "a reduced hazard of developing dry AMD among patients with depression who were treated with fluoxetine." Senior author of the study remarks, “[W]e may have only begun to scratch the surface of finding new uses for old drugs. It is tempting to think about all the untapped therapeutic potential of medicines sitting on pharmacy shelves...Ultimately, the best way to test whether fluoxetine benefits macular degeneration is to run a prospective clinical trial.”

My rating of this study: ⭐⭐⭐🌸

Ambati M, Apicella I, Shao Wang S, et al. "Identification of fluoxetine as a direct NLRP3 inhibitor to treat atrophic macular degeneration." PNAS.  118(41):e2102975118. 12 October 2021. https://doi.org/10.1073/pnas.2102975118