Parkinson's drug prevents and slows macular degeneration

By John Murphy, MDLinx
Published November 16, 2015

Key Takeaways

In a retrospective study of thousands of patient records, researchers have found that patients taking L-DOPA, used to treat Parkinson’s disease, were less likely to develop age-related macular degeneration (AMD). Also, among patients taking L-DOPA who did develop AMD, the age of onset was significantly delayed.

“Research points to this as a pathway to regulate and prevent this most common cause of blindness in adults,” said co-principal investigator Murray Brilliant, PhD, Director of the Marshfield Clinic Research Foundation Center for Human Genetics, Marshfield, WI. “Imagine telling patients we potentially have medication that will allow them to see and continue enjoying life, their family, and perform every day activities as they age. That is very powerful.”

Results of the study were published online October 30, 2015 in American Journal of Medicine.

This line of investigation began when the researchers discovered that the retinal pigment epithelium expresses a receptor for L-DOPA, and that this signaling pathway fosters retinal survival. The researchers questioned whether L-DOPA may offer a protective effect against AMD.

To find out, they undertook what they called a “virtual prospective clinical trial” in which they reviewed the health records of 37,000 patients from the Marshfield Clinic to determine who had macular degeneration, who took L-DOPA, or both.

Their analysis showed that patients who began taking L-DOPA before they developed macular degeneration were diagnosed with AMD 8 years later than those who had never taken L-DOPA. They also found that there were many fewer AMD patients in the group that were prescribed L-DOPA.

They next confirmed these results using a much larger, insurance-industry database of 87 million patients, and found the same associations between L-DOPA and AMD. Analysis from this huge data set also showed that L-DOPA appeared to both prevent and delay the wet form of AMD, which is far less common than dry AMD but is responsible for about 90% of AMD-caused blindness.

The authors acknowledged that this study could not explain L-DOPA’s mechanism of action on the incidence of AMD. But, they noted, the only known receptor in the retina for L-DOPA is GPR143, and “signaling through GPR143 simultaneously increases PEDF [pigment epithelium-derived factor] secretion while decreasing VEGF [vascular endothelial growth factor], providing a plausible biological explanation for the ameliorating effect of L-DOPA on the retina.”

“This study suggests an intriguing link between patients taking L-DOPA and a lower incidence and delayed onset of AMD,” said Paul A. Sieving, MD, PhD, Director of the National Eye Institute, which helped to fund the study. “Showing that L-DOPA causes this protective effect will require further investigation, but if confirmed, could lead to new drugs or combination therapies for AMD that target DOPA-responsive cells in the retina.”

The next step in this research will be to perform a clinical trial to determine the extent of L-DOPA’s ability to prevent AMD. Because the drug is already approved as the mainstay treatment for Parkinson’s disease, repositioning it as a treatment for AMD may hasten its progress. 

“Results suggest a new path forward in our fight against AMD that may even include a strategy to prevent those at risk of the disease from ever developing it,” said co-principal investigator Brian McKay, PhD, Associate Professor of Ophthalmology and Vision Science at the University of Arizona, in Tucson, AZ. “In the end, L-DOPA may not be the drug that ends the disease but the pathway identified is likely to be a key observation as the search for a cure continues.”

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