University of Kentucky's Charles Coomer is the first UK MD/PhD student to be accepted into...
Nucleoside reverse transcriptase inhibitors (NRTIs) are mainstay therapeutics for HIV that block retrovirus replication. Alu (an endogenous retroelement that also requires reverse transcriptase for its life cycle)-derived RNAs activate P2X7 and the NLRP3 inflammasome to cause cell death of the retinal pigment epithelium in geographic atrophy, a type of age-related macular degeneration. We found that NRTIs inhibit P2X7-mediated NLRP3 inflammasome activation independent of reverse transcriptase inhibition. Multiple approved and clinically relevant NRTIs prevented caspase-1 activation, the effector of the NLRP3 inflammasome, induced by Alu RNA. NRTIs were efficacious in mouse models of geographic atrophy, choroidal neovascularization, graft-versus-host disease, and sterile liver inflammation. Our findings suggest that NRTIs are ripe for drug repurposing in P2X7-driven diseases.
Copyright © 2014, American Association for the Advancement of Science.
Fowler, Benjamin J., Bradley D. Gelfand, Younghee Kim, Nagaraj Kerur, Valeria Tarallo, Yoshio Hirano, Shoba Amarnath et al. "Nucleoside reverse transcriptase inhibitors possess intrinsic anti-inflammatory activity." Science346, no. 6212 (2014): 1000-1003.
Ben Fowler has completed his PhD and is now returning to medical school to complete his training.
"I study non-coding RNA biology in the context of a disease called age-related macular degeneration. Some of my research interests include the host cell response to retrotranposons and the plasticity and intra-individual divergence of the somatic genome."