HIV/AIDS drugs that are FDA approved could treat age-related macular degeneration

from washington.edu

A study published in the journal Science by an international group of scientists, led by the laboratory of Dr. Jayakrishna Ambati, professor and vice chair of the Department of Ophthalmology & Visual Sciences at the University of Kentucky, reports that HIV/AIDS drugs that have been used for the last 30 years could be repurposed to treat age-related macular degeneration (AMD), as well as other inflammatory disorders, because of a previously undiscovered intrinsic and inflammatory activity those drugs possess.

Nucleoside reverse transcriptase inhibitors (NRTIs) are the most widely used class of anti-HIV drugs. NRTIs are thought to be therapeutic in HIV/AIDS patients because they target the enzyme reverse transcriptase, which is critical for replication of HIV. Previous work from the Ambati lab found that a type of toxic molecule called Alu RNA accumulate in the retina to cause dry AMD; interestingly, Alu RNA and HIV are similar in that they both require reverse transcriptase to fulfill their life cycle.

In their publication, the authors report that multiple FDA-approved NRTIs prevented retinal degeneration in a mouse model of dry AMD. Surprisingly, this effect of NRTIs in the eye was not due to the well-known function of these drugs to inhibit reverse transcriptase. Instead, NRTIs blocked an innate immune pathway called the “inflammasome”, even in experimental systems in which the NRTIs were not capable of blocking reverse transcriptase.

In their report, the authors also showed that NRTIs were effective in other disease models that share common signaling pathways with the dry AMD model, including wet AMD and graft-versus-host disease which is the major obstacle preventing successful allogeneic hematopoietic stem cell transplantation.

Repurposing of NRTIs for treating AMD could be advantageous since they are very inexpensive. Moreover, through decades of clinical experience, the drugs tested should be safe. Since these NRTIs are already FDA-approved, they could be rapidly and inexpensively translated into therapies for a variety of untreatable or poorly treatable conditions.

NRTIs were originally designed to treat cancer in the 1960s. They re-emerged in the late 1980s and became the first drugs FDA-approved to treat HIV/AIDS.

This study was funded by the National Institutes of Health.