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HIV drug may also treat macular degeneration

Reporting their findings in the journal Science, the international team, led by researchers at the University of Kentucky in Lexington, say because of a previously undiscovered property, the drugs may also be effective against other inflammatory disorders.

A major cause of vision loss among the elderly, age-related macular degeneration (AMD) is a progressive condition that is untreatable in up to 90% of patients. As AMD progresses, patients find their central vision becomes increasingly blurred and they struggle to read print, recognize people’s faces and drive a car.

There are two types of AMD: dry and wet. Dry is the most common and least serious form – it progresses slowly and accounts for 90% of cases. Wet AMD is more serious, and without treatment can progress very quickly. It develops when abnormal blood vessels invade the retina and cause cell damage.

Several robust treatments exist for wet AMD – thanks to a detailed understanding of its molecular mechanisms, say the researchers. In contrast, there are currently no approved treatments for dry AMD.

The study tested the effect of NRTIs on dry AMD in mice

The new study demonstrates that FDA-approved NRTIs stopped retinal degeneration, and researchers were surprised to find it was a previously unknown property of the drugs that produced the results.

In this latest study, senior author Jayakrishna Ambati, professor and vice chair of Kentucky’s Department of Ophthalmology and Visual Sciences, and colleagues investigated a class of drugs known as nucleoside reverse transcriptase inhibitors (NRTIs).

NRTIs are the most widely used drugs for treating HIV/AIDS. They are thought to be effective because they target reverse transcriptase – an enzyme that is important for HIV replication.

Antirretrovirais
The new study demonstrates that FDA-approved NRTIs stopped retinal degeneration, and researchers were surprised to find it was a previously unknown property of the drugs that produced the results.

NRTIs have been around for decades. They were originally developed and used in the 1960s to treat cancer and then, in the late 1980s, they were the first drugs to receive federal approval for the treatment of HIV/AIDS.

In previous work, Prof. Ambati’s lab had discovered the toxic molecule Alu RNA collects in the retina to cause dry AMD. Alu RNA is similar to HIV in that both need the reverse transcriptase enzyme to complete their life cycle.

In their new study on mice with a condition similar to dry AMD, Prof. Ambati and colleagues show that several FDA-approved NRTIs stopped retinal degeneration. But they were surprised to find it was a previously unknown property of the drugs that produced the results.

They found the NRTIs blocked a type of inflammasome called NLRP3. Inflammasomes are large complexes of proteins that play a key role in innate immunity. They detect and respond to certain molecular patterns of pathogens and other damaging agents.

NRTIs blocked inflammasome independently of reverse transcriptase inhibition

The authors note they found NRTIs blocked inflammasome activation even in experiments where the drugs could not block reverse transcriptase.

They also showed that NRTIs were effective in other diseases that have similar signaling pathways to the version of dry AMD they induced in the mice. This includes the wet form of AMD and graft-versus-host disease, a common complication in bone marrow transplant and other types of tissue graft.

Benjamin Fowler, lead author of the study and a postdoctoral fellow in Prof. Ambati’s lab, says there could be several advantages to re-purposing NRTIs. For one, they are relatively cheap, and:

 

[quote font=”play” font_style=”italic” bcolor=”#dd3333″ arrow=”yes” align=”center”]”Moreover, through decades of clinical experience, we know that some of the drugs we tested are incredibly 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.”[/quote]

 

Meanwhile, Medical News Today recently learned of another study that showed macular degeneration may respond to new laser therapy. The researchers said the new low-impact, low-energy laser treatment they tested showed promising results in patients with early AMD without damaging the retina.

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