Anti-HIV drugs appear to prevent number one cause of vision loss in older people

When the pandemic began, there were no approved drugs to treat COVID-19, and developing them from scratch would take time – time that many patients did not have.

So the doctors began to work with the drug they made have, prescribing drugs approved off-label. This led to the discovery of the first life-saving coronavirus drug: a common steroid that had been on the market for decades.

However, the drug reorientation did not start with the pandemic.

Researchers are increasingly studying existing drugs, looking for effects that could treat other diseases. It’s faster and cheaper than developing a new drug from scratch, but the result is the same: healthier patients.

Earlier examples of drug reuse include aspirin, which started as a pain reliever but is now used to prevent heart attacks, and Viagra, which is more commonly known as an erectile dysfunction drug but can also treat one type high blood pressure.

Now, researchers have made another potential breakthrough in drug reorientation: Drugs developed to treat HIV may be able to treat an incurable, vision-impairing disease called dry macular degeneration.

Dry macular degeneration

Age-related macular degeneration is the most common cause vision loss in people over 50. It comes in two forms – “wet” and “dry” – and although the dry form is less severe, it is also much more common, affecting more people. 200 million people worldwide.

In its advanced stage, known as “geographic atrophy,” dry macular degeneration causes blind spots in a person’s vision.

This can then progress to the point where their central vision is completely gone – they can still see things in their peripheral vision, but not what is directly in their field of vision – and it can prevent them from driving, reading, working. , and even live alone.

There is currently no treatment or cure for dry macular degeneration, but now an international team of scientists has released a to study in the PNAS review suggesting that a drug used to treat HIV may be able to help.

Unwanted DNA

Some of the DNA in our cells contains instructions for making the proteins that power all of our bodily functions. But the large majority DNA is undesirable.

Seriously.

People taking anti-HIV drugs were 40% less likely to develop dry macular degeneration.

“Junk DNA” is the term used to describe non-coding DNA – that is, the type that doesn’t tell our cells to make proteins – and it wasn’t until recently that researchers started to understand what this DNA actually does.

In 2011, the team behind the PNAS paper discovered that the buildup of an unwanted type of DNA (called “Alu”) in cells around the retina contributes to dry macular degeneration. This build-up occurs outside the nucleus of cells, in an area called the cytoplasm.

Several diseases have been linked to the presence of DNA in the cytoplasm, so researchers wondered whether it would be possible to reuse a drug for one of these diseases to treat dry macular degeneration.

Drug reassignment

One type of drug – nucleoside reverse transcriptase inhibitors (NRTIs) – caught their attention. Approved for use as a treatment for HIV, the drugs are also known to prevent Alu DNA replication.

In 2014, researchers NRTIs tested in mice with symptoms of macular degeneration and found that the drugs could effectively treat animals – but, surprisingly, not because they affected Alu DNA, but because they blocked a group of proteins called inflammasome.

For their most recent study, the researchers looked at Medicare databases with data on more than 100 million patients collected over two decades to see if there was a link between NRTI use and dry macular degeneration in people.

From this review, they found that people taking the drugs were almost 40% less likely to develop a vision-impairing disease than similar people not taking the drugs.

Dry macular degeneration can cause a person to completely lose their central vision.

An observational study like this does not prove causation, as people taking the drugs could be different in many ways that researchers cannot see or control. But coupled with the mouse study, it looks very promising.

They are now hoping to start clinical trials to test the ability of NRTIs and their safer derivatives (called ‘Kamuvudins’) to treat dry macular degeneration – but they believe that anti-HIV drugs could help treat other conditions as well. related to the inflammasome. .

“We believe that kamuvudins may be effective against a large number of widespread degenerative diseases involving activation of the inflammasome, such as multiple sclerosis, Alzheimer’s disease and type 2 diabetes,” researcher Jayakrishna Ambati said in a press release.

Since NRTIs have already gone through the development process once, it also wouldn’t take that long – or that much money – to get them approved for treating dry macular degeneration in humans.

“If we started a trial today and NRTIs were effective in treating (age-related macular degeneration), they could be approved for use in as little as 2-3 years, for less than 10 million. dollars, ”the researchers explain. written in Fortune after their study on mice.

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