Novel Antiangiogenic Compounds for Treatment of Choroidal Neovascularization
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 new chemical that we developed that blocks blood vessel growth, we will design and produce related chemicals that are even more potent and selective for blood vessel cells over other cell types. We will then determine the best dosage regimen for two of these compounds to maximize their levels and effects in the eye, en route to developing a new therapy for AMD.
The overarching goal of our work is to develop a promising new therapy for “wet” age-related macular degeneration (AMD). Building on a new chemical we developed that blocks blood vessel growth, we are designing and producing related chemicals that are even more potent and also selective for blood vessel cells over other cell types. We are testing these chemicals in cells to demonstrate effectiveness and selectivity for stopping the growth of blood vessel cells without killing cells outright. We can then test top candidate chemicals in a model of choroidal neovascularization, the type of abnormal blood vessel growth seen in wet AMD. Next, we will determine the best dosage regimen for two of these compounds to maximize their levels in the eye. We will follow these experiments by confirming that this dosage has maximal effect.
We are excited about this work, as our “lead” chemical is new and very promising as a potential drug candidate for AMD treatment. The chemical appears to act in an unexpected way, and could therefore potentially be combined with drugs that work by other mechanisms to increase therapeutic benefit. We hope our experiments will serve to make our chemical even more powerful and safe and nearly ready for human trials. Our work will benefit the research field by establishing that our chemical has potential as a treatment for wet AMD. This will help spur others to work on similar chemicals with similar mechanisms. Our work will then benefit the wider community by validating our approach as a new way to treat this blinding eye disease. This may then lead to effective and safe new drugs.
About the Researcher
Tim Corson, PhD, is an assistant professor in the Eugene and Marilyn Glick Eye Institute and in the Department of Ophthalmology, Biochemistry and Molecular Biology, and the Department of 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. In addition receiving funding from the BrightFocus Foundation, his work has been supported by the International Retinal Research Foundation, Retina Research Foundation, and a National Institutes of Health career development award.
"It is a source of continual wonder and immense gratitude for me that donors provide such generous support for research. Sometimes, this comes as a result of their extensive interactions with researchers and the underlying science of a disease; but often, it comes from personal and family exposure to a disease and a hope that something – anything – can be done. In the latter case, there is thus an immense responsibility that we, as researchers, must take on to ensure that we do the best, most impactful work we can with the philanthropic dollars entrusted to us. We must squeeze as much research value as possible out of the funds we are privileged to receive. Fortunately, this imperative to be efficient with funding is entirely consistent with “doing good science”: how can we design experiments to efficiently and conclusively answer important research questions that will help prevent and treat disease? This is the question that we ask every day, and our donors’ generosity demands nothing less."
First published on: July 15, 2015
Last modified on: July 1, 2017