HIV drug may also treat macular degeneration

Date: Nov-21-2014 A landmark study shows that a class of drugs that has been used to treat

HIV/AIDS for 30 years could be re-purposed as a treatment for age-related macular

degeneration - a leading cause of blindness among the elderly worldwide.

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.

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

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.

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:

"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."

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.

Written by Catharine Paddock PhD

Not to be reproduced without permission.

Follow @twitter

window.twttr = (function (d, s, id) {
var t, js, fjs = d.getElementsByTagName(s)[0];
if (d.getElementById(id)) return;
js = d.createElement(s); js.id = id;
js.src= "https://platform.twitter.com/widgets.js";
fjs.parentNode.insertBefore(js, fjs);
return window.twttr || (t = { _e: [], ready: function (f) { t._e.push(f) }
}(document, "script", "twitter-wjs"));

Courtesy: Medical News Today Note: Any medical information available in this news section is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional.