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BrightFocus-Supported Researchers Show Link Between Parkinson’s Drug and Curbing Macular Degeneration

This research was supported by BrightFocus

L-DOPA Clinical Trial Ahead?

Since October, when the article by BrightFocus grantee Brian McKay, PhD, et al was published in the American Journal of Medicine, he has been interviewed frequently about the potential therapy. “I think in the end we’re going to be able to prevent AMD,” he told U.S. World and News Report on December 10. “But we have more work to do.”

On Monday, December 21, McKay was one of the speakers on a BrightFocus Chat, Research Roundup: Treatments for the Future.

Up ahead, McKay has been asked to consult on a multi-center clinical trial to test whether L-DOPA can prevent the progression of AMD.

Funding is currently sought for that trial, planned by  Tucson-based ophthalmologist, Robert Snyder, MD, PhD, and his Snyder Biomedical Corp. Recruitment is not yet underway; however, a registry is being created of people who agree to have their AMD evaluated using laser scans and auto-fluorescent photos. No treatment is offered as part of registering, but qualifying individuals may be referred to the upcoming L-DOPA trial.

A major new breakthrough shows that L-DOPA, a drug widely used to treat Parkinson’s disease, may help protect against age-related macular degeneration (AMD). The discovery was made by a group of researchers led by Brian McKay, PhD, and just published in the American Journal of Medicine (Brilliant et al, 2015).

The research team, supported in part by BrightFocus Foundation, discovered a biological connection between darker pigmented eyes that are known to be resistant to AMD, and increased levels of a chemical called L-DOPA in those eyes. Since L-DOPA is frequently prescribed for Parkinson’s patients, the researchers wanted to know whether patients who received the drug L-DOPA as treatment for Parkinson’s or other diseases were protected from AMD.  By combing through massive databases of medical chart data, they reported that patients receiving L-DOPA were significantly less likely to get AMD, and when they did, its onset was significantly delayed. 

The research findings are based on an analysis of the medical records of 37,000 patients at the Marshfield Clinic in Wisconsin.  Because the average age of those given L-DOPA is 67, while the average age of AMD diagnosis is 71, scientists were able to effectively track patterns.  These major findings were then confirmed by reviewing a data set of 87 million patients.  In this large scale data set, L-DOPA also delayed or prevented AMD from progressing to its “wet” form.

Brian McKay, PhD, led the investigation, which got started with his BrightFocus grant.
Brian McKay, PhD, led the investigation, which got started with his BrightFocus grant.
According to McKay, “we asked the question: ‘Are those taking L-DOPA protected from AMD?’ The answer was yes!  L-DOPA both prevented and delayed the onset of AMD.”

New Hope for an AMD Treatment

L-DOPA is available worldwide and goes by the generic name of levodopa. Brand names include Sinemet, Parcopa, Atamet, Stalevo, Madopar, and Prolopa.

Despite persistent, dedicated work by scientists, it has been longer than a decade since a new type of drug was developed for AMD, and scientists still do not understand precisely what causes it.  AMD remains a chief cause of legal blindness in adults over age 60.  While leaving peripheral sight intact (i.e. the edges of one’s visual field), it destroys the center. The resulting black hole makes people unable to drive, read, recognize faces and perform daily tasks.

The only measures currently available to stall and sometimes prevent AMD are the AREDS-proven vitamins for early AMD, and scheduled eye injections for the neovascular form, known as “wet” AMD.

Trail of Discovery Begins with BrightFocus Grant

McKay, a 2010-12 BrightFocus grantee, started working on the project at a time when investigators were realizing the huge importance of the retinal pigmented epithelium (RPE), a layer of cells next to the retina, to the retina’s health and survival.  McKay was looking for molecular pathways that regulate “trophic factors,” proteins associated with tissue nourishment and growth.

They discovered that one way the RPE cells help keep the retina healthy is with DOPA signaling through its receptor. In the body, protein molecules such as L-DOPA bind with each other through receptors, or docking stations that lie on cells.  Receptor binding is both the result of, and sets in motion, gene signaling. Actions and reactions of this sort direct most functions of the human body., and unlocking their secrets helps scientists uncover how a disease begins and progresses, and where it can be stopped.

For a long time it has been recognized that individuals with darker pigmentation have a lower risk for AMD; in the United States, African-Americans have a five-fold lower risk of AMD than Caucasians. This led researchers to postulate that signaling through the DOPA receptor may underlie racial disparities in AMD incidence. From there grew the hypothesis that people taking L-DOPA for other conditions would be protected against AMD.

“The obvious question was, if the L-DOPA no longer produced was supplemented via pill form, does it have the potential to serve as a preventive medicine against AMD?” commented Murray Brilliant, PhD, first author on the report, who directs the Marshfield Clinic Research Foundation Center for Human Genetics.

To test that hypothesis, these researchers first examined the health records of 37,000 patients at the Marshfield Clinic, comparing outcomes among patients who had AMD, or were taking L-DOPA for Parkinson’s or another condition, or both.  These researchers found that among people who got L-DOPA before being diagnosed with AMD, their AMD diagnosis occurred eight years later than those not taking L-DOPA. 

These provocative findings were then confirmed in a much larger data set of 87 million patients, where similar results were observed. Next, the study was expanded to investigate the association between L-DOPA use and prevention and delay of “wet” AMD, the most devastating form of the disease. And once again, L-DOPA was found to be protective.

“Research points to this as a pathway to regulate and prevent this most common cause of blindness in adults,” Brilliant said. “We need more research, but this first step is promising.”

Shows Power of “Big Data”

“Big data” research methods use customized computer programs to search through millions of electronic medical records and analyze their contents. This research method helped compare the analysis of the 37,000 Marshfield files with an exponentially larger pool of 87 million medical records.  This big data exercise confirmed the research team’s initial conclusions. 

Commenting on the study’s methodology, Guy Eakin, BrightFocus vice president for Scientific Affairs, said the researchers groundbreaking accomplishments show how this new approach can, “quickly ask the scientific questions that had previously taken many years and millions of dollars.”

The next stage for the research team is to launch a clinical trial to further test the ability of L-DOPA to slow or prevent AMD.  Continued success of this hypothesis could lead to a new and life-changing example of what is known as drug repurposing or repositioning, in which scientists identify new uses for existing drugs.

This content was first posted on: November 9, 2015

The information provided in this section is a public service of BrightFocus Foundation, and should not in any way substitute for the advice of a qualified healthcare professional, and is not intended to constitute medical advice. Although we take efforts to keep the medical information on our website updated, we cannot guarantee that the information on our website reflects the most up-to-date research. Please consult your physician for personalized medical advice; all medications and supplements should only be taken under medical supervision. BrightFocus Foundation does not endorse any medical product or therapy.

Some of the content in this section is adapted from other sources, which are clearly identified within each individual item of information.

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