In some forms of retinopathy, blood vessels grow out of control in the eye, blocking light and causing irreversible vision loss. This condition sometimes occurs in premature babies and in adults with diabetes.
Now scientists from the Oklahoma Medical Research Foundation (OMRF) are reporting they’ve discovered a way to treat those abnormal blood vessels in mice with an experimental small molecule that blocks proteins in the eye that cause the vessels to grow out of control. The drug tamped down the growth of abnormal blood vessels while leaving healthy ones alone, they reported in the journal Proceedings of the National Academy of Sciences.
The researchers started by analyzing a set of blood vessels in mice that naturally disappear shortly after birth. In doing so, they identified specific proteins called endothelial ETS transcription factors, which diminished as those blood vessels started to recede, the researchers discovered. They guessed that the proteins act as an off switch of sorts, and started looking for ways to replicate the process in retinopathy models.
That led them to an experimental compound called YK-4-279, which inhibits multiple ETS transcription factors. When they tried it in the mouse models, it inhibited the growth of the blinding blood vessels. What’s more, it seemed to impact only the vessels with abnormally slow blood flow—a sign of vessels consistent with retinopathy. The normal vessels the eye needs to maintain health were not affected.
“We wanted to trick blood vessels in diseased mice into thinking they were supposed to be regressing and naturally dying off,” said Chris Schafer, Ph.D., a postdoctoral researcher at OMRF, in a statement. "This appears to be what happened."
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Retinopathy can occur in premature babies because of high oxygen levels in incubators that interfere with normal blood vessel development in the eye. But the condition often resolves itself over time. In adults with diabetes, though, retinopathy can be a lifelong problem, causing vision loss that can’t be reversed.
Among the companies working on solutions for diabetic retinopathy is OccuRx, which is testing a pill to treat both that disease and age-related macular degeneration. The drug, OCX063, targets signals associated with inflammation and has been shown in rat models to reduce leakage from abnormal blood vessels in the eye.
There have been some disappointments, though. Last March, Aerpio Pharmaceuticals announced that its retinopathy drug AKB-9778 missed its primary endpoint in a mid-phase trial.
The OMRF team said in the new study that they believe YK-4-279 might not only diminish abnormal blood vessels in the eye but also directly stimulate the growth of normal blood vessels. They are now planning future studies to investigate that possibility.