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Parkinson’s Drug Could Help Save Sight

New study: Leading cause of blindness could be prevented or delayed.

In a major scientific breakthrough, a drug used to treat Parkinson’s and related diseases may be able to delay or prevent macular degeneration, the most common form of blindness among older Americans.

The findings, published in the American Journal of Medicine, are a groundbreaking effort in the fight against age-related macular degeneration (AMD), which affects as many as 11 million Americans. AMD hinders central vision, and even when it does not lead to blindness it can severely reduce the ability to read, drive, and recognize faces.

In the study, supported in part by BrightFocus Foundation, researchers discovered a biological connection between darker pigmented eyes, which 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.

“Rather than looking at what might cause AMD, we instead wondered why certain people are protected from AMD. This approach had never been done before,” says senior author Brian McKay of the University of Arizona.

The research findings are based off 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, the most devastating form of the disease.

Image of a woman's eye.

Researchers discovered a biological connection between darker pigmented eyes, which are known to be resistant to AMD, and increased levels of a chemical called L-DOPA in those eyes. Image is for illustrative purposes only.

“This exciting breakthrough shows the power of scientific discovery to give hope to millions of people across the nation and the world. Their methodology is a reminder that ‘big data’ is not a buzzword – it is a bold and innovative new approach to science,” said BrightFocus president and CEO Stacy Pagos Haller.

The next steps for the team of scientists is to launch a clinical trial to further test the ability of this drug to prevent AMD. The title of their research paper is “Mining Retrospective Data for Virtual Prospective Drug Repurposing: L-DOPA and Age-related Macular Degeneration.”

About this neuroscience research

Funding: The research was funded by BrightFocus Foundation.

Source: Alice Kirkman – BrightFocus Foundation
Image Credit: The image is in the public domain
Original Research: Full open access research for “Mining Retrospective Data for Virtual Prospective Drug Repurposing: L-DOPA and Age-related Macular Degeneration” by Murray H. Brilliant, Ph.D., Kamyar Vaziri, MD., Thomas B. Connor Jr., MD, Stephen G. Schwartz, MD, MBA, Joseph J. Carroll, Ph.D., Catherine A. McCarty, Ph.D., MPH., Steven J. Schrodi, Ph.D., Scott J. Hebbring, Ph.D., Krishna S. Kishor, MD., Harry W. Flynn Jr., MD., Andrew A. Moshfeghi, MD., Darius M. Moshfeghi, MD., M Elizabeth Fini, Ph.D., and Brian S. McKay, Ph.D. in American Journal of Medicine. Published online October 30 9 2015 doi:10.1016/j.amjmed.2015.10.015


Abstract

Mining Retrospective Data for Virtual Prospective Drug Repurposing: L-DOPA and Age-related Macular Degeneration

Background
Age-related Macular Degeneration (AMD) is a leading cause of visual loss among the elderly. A key cell-type involved in AMD, the retinal pigment epithelium expresses a g-protein coupled receptor that, in response to its ligand, L-DOPA, upregulates pigment epithelia derived factor, while downregulating vascular endothelial growth factor. In this study we investigated the potential relationship between L-DOPA and AMD.

Methods
We used retrospective analysis to compare the incidence of AMD between patients taking vs. not taking L-DOPA. We analyzed 2 separate cohorts of patients with extensive medical records from the Marshfield Clinic (∼17,000 and ∼20,000) and the Truven MarketScan outpatient and databases (∼87 million) patients. We used ICD-9 codes to identify AMD diagnoses and L-DOPA prescriptions to determine the relative risk of developing AMD and age of onset with or without an L-DOPA prescription.

Results
In the retrospective analysis of patients without an L-DOPA prescription, AMD age of onset was 71.2, 71.3 and 71.3 in three independent retrospective cohorts. AMD occurred significantly later in patients with an L-DOPA prescription, 79.4 in all cohorts. The odds ratio of developing AMD was also significantly negatively correlated by L-DOPA (OR=0.78;CI=0.76-0.80;P<0.001). Similar results were observed for neovascular AMD, p<0.001.

Conclusion
Exogenous L-DOPA was protective against AMD. L-DOPA is normally produced in pigmented tissues such as the retinal pigment epithelium as a byproduct of melanin synthesis by tyrosinase. GPR143 is the only known L-DOPA receptor, it is therefore plausible that GPR143 may be a fruitful target to combat this devastating disease.

“Mining Retrospective Data for Virtual Prospective Drug Repurposing: L-DOPA and Age-related Macular Degeneration” by Murray H. Brilliant, Ph.D., Kamyar Vaziri, MD., Thomas B. Connor Jr., MD, Stephen G. Schwartz, MD, MBA, Joseph J. Carroll, Ph.D., Catherine A. McCarty, Ph.D., MPH., Steven J. Schrodi, Ph.D., Scott J. Hebbring, Ph.D., Krishna S. Kishor, MD., Harry W. Flynn Jr., MD., Andrew A. Moshfeghi, MD., Darius M. Moshfeghi, MD., M Elizabeth Fini, Ph.D., and Brian S. McKay, Ph.D. in American Journal of Medicine. Published online October 30 9 2015 doi:10.1016/j.amjmed.2015.10.015

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