A University of Kentucky research team has discovered the first treatment for what they call the silent epidemic of macular degeneration by finding a new purpose for an old drug.
The treatment uses AZT, a drug used for fighting HIV, to treat the chronic eye disease.
"It really has the potential to change the lives of millions of people," said Dr. Jayakrishna Ambati, an associate professor of ophthalmology who leads the team.
Since the discovery was made public in late November, Ambati has been receiving inquires from across the globe.
"We are actively collaborating with people around the world," he said.
Ambati hopes to have AZT approved for treatment in 18 to 24 months. He is also working with the UK College of Pharmacy to create a sustainable release device to be implanted in the eye to provide a steady dose of the drug.
Macular degeneration is an age-related disease that affects about 10 million Americans, said Ambati. That number is expected to double during the next decade as baby boomers age.
What Ambati and his team discovered is that there is a Dicer enzyme responsible for keeping unwanted Alu from building up in the retinal cells in the eye. When the level of the Dicer enzyme drops, the Alu start to accumulate. It is the same principle, Ambati said, as having your trash build up on the sidewalk because the garbage man doesn't come week after week.
As that happens in the eye, it loses the ability to see fine details clearly, which can harm a person's ability to read, drive and perform everyday tasks. People might experience blurriness or darkness in the center of their vision.
What Ambati's team learned in studying this growth was that Alu replicates itself. The "aha" moment of the research came when someone mentioned that HIV cells replicate in much the same way. From there the discussion led to the idea of using AZT, a drug long used to stop HIV cells from replicating, to see whether it would treat macular degeneration.
The thought was really "wouldn't it be interesting to see what happens with it," he said. It would work or it wouldn't work.
"There was really no subtlety to this," he said.
It did work. The drug primarily used for treating HIV helped stem retinal damage. But, Ambati said, further exploration showed that it worked not in the way researchers originally expected.
The chemicals that help stop the replication also have "another moonlighting job," he said. That job is blocking inflammasomes that stress the eye and contribute to degeneration.
The basic premise on how the drug is working has potential implications for other diseases such as Alzheimer's and cancer, Ambati said. He and his team are talking with their colleagues about how the research findings might be widely useful.
Because animal models and early human testing for AZT as treatment for macular degeneration is positive, Ambati is heading a larger clinical trial in humans starting in the first three months of 2015.
It will be the first treatment for macular degeneration, he said, and he hopes it will give hope to people who think that dimming eyesight is a natural part of aging.
But that doesn't mean his work is over. Ambati is now trying to find the $10 million he needs to complete the research.
While the FDA is encouraging research to find novel uses for existing drugs, it's not something that appeals to many investors. In Ambati's case, AZT is a generic drug, so even though many millions more might use it, investors won't get a big payoff.
Dan Wermeling, a professor of pharmacy, said Ambati's problem was not unusual. Wermeling helped develop a nasal spray to stop heroin and other opioid overdoses, which is being fast-tracked by the FDA. In that case, the drug was known, but the delivery system was new.
Much of the low-hanging fruit in drug discoveries has been picked, he said. It can be easier and quicker to find new uses for old drugs.
But, as Ambati's case shows, it can be challenging to find funding. A researcher has to focus on the science and business model that will work.
The issue of finding funding for novel uses of drugs but that aren't attractive to investors is "something society is going to have to wrestle with going forward," Ambati said.
For his part, he is sure he will get this groundbreaking treatment approved and in the hands of people it can help.
"This will happen," he said. "It is too important not to happen."