A New Way to Target Abnormal Blood Vessel Growth in Wet Macular Degeneration

Tim Corson, PhD
Indiana University School of Medicine (Indianapolis, IN)
Year Awarded:
2019
Grant Duration:
July 1, 2019 to June 30, 2021
Disease:
Macular Degeneration
Award Amount:
$200,000
Grant Reference ID:
M2019069
Award Type:
Standard
Award Region:
US Midwestern
Tim Corson

Inhibiting a Novel Target for Wet AMD Therapy

Summary

Abnormal blood vessel growth in the eye causes “wet” age-related macular degeneration, a major cause of blindness. Since many patients do not respond to existing therapies, new drugs are needed to block this blood vessel growth. Starting with a protein that we discovered that blocks blood vessel growth when inhibited, we will design and produce new chemicals that block this protein’s function. We will test these chemicals for blood vessel growth inhibition in the petri dish and in eyes, as a key step towards developing a new therapy for wet AMD.

Details

The overarching goal of our work is to develop a new kind of therapy for “wet” age-related macular degeneration (AMD). This disease is caused by abnormal blood vessel growth in the eye, and we have found a protein called ferrochelatase that is important for this abnormal growth. Building on a new chemical we developed that blocks ferrochelatase activity, we are designing and producing related chemicals that are even more potent. We are testing these chemicals in cells to show effectiveness and selectivity for stopping the growth of blood vessel cells without killing cells outright. We can then test top candidate chemicals as eyedrops in a model of choroidal neovascularization, the type of abnormal blood vessel growth seen in wet AMD. We will follow these experiments by determining if our chemical can cooperate with the existing drugs used for treating this disease.

We are excited about this work, as ferrochelatase is a new and very promising target for wet AMD. We are the first to develop chemicals inhibiting ferrochelatase for wet AMD, and we hope our experiments will yield new chemicals that can be moved toward human trials. Our work will benefit the research field by establishing that ferrochelatase targeting has potential as a treatment for wet AMD. This will help spur others to work on this protein. Our work will then benefit the wider community by validating our approach as a new way to treat wet AMD, which may then lead to effective and safe new drugs.

About the Researcher

Dr. Corson is the Merrill Grayson Senior Associate Professor and Director of Basic and Translational Research in the Eugene and Marilyn Glick Eye Institute and Departments of Ophthalmology, Biochemistry and Molecular Biology, and Pharmacology and Toxicology at Indiana University School of Medicine in Indianapolis, Indiana. After growing up in Australia, England, New Zealand, and Canada, he completed BSc, MSc and PhD degrees at the University of Toronto, where he studied genetic changes in the eye cancer, retinoblastoma. Subsequently, as the Canadian Institutes of Health Research Jean-François St-Denis Fellow in Cancer Research at Yale University, he learned to apply chemical biology approaches (the use of chemicals to probe biological systems) to diverse disease-related problems. In his own laboratory, he applies these techniques to mechanistic and therapeutic studies of antiangiogenic natural products and their derivatives, with the goal of developing new therapies for diseases of abnormal blood vessel growth such as AMD and ocular tumors. He has published more than 50 papers and filed 8 patents. In addition to the BrightFocus Foundation, his work has been supported by the International Retinal Research Foundation, the Retina Research Foundation, and the National Institutes of Health.

Personal Story

 To me, it is an exciting time in AMD research. Decades of fundamental research discoveries have been successfully translated into powerful therapies such as the anti-VEGF drugs for wet AMD already in use and the first drugs for dry AMD now nearing the clinic. These successes give me hope, not just for the patients who benefit from them directly, but also for the precedent that they set for finding newer, improved drugs. It is this hope that keeps me excited about our research projects in this area – hope that we can help develop the next vision-saving therapy for AMD.

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