Inhibiting a Novel Target for Wet AMD Therapy

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.

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.