Animal studies of a new compound, which can be delivered by eye drop, have found that it can reverse epigenetic changes that lead to wet age-related macular degeneration.
A new compound developed by the University of Illinois at Chicago has the potential to treat wet age-related macular degeneration (AMD) without injections. Age-related macular degeneration occurs when the macula, part of the retina at the back of the eye, becomes damaged. About 10% of all cases become wet, which leads to vision loss as a result of excess blood vessel growth between two layers of cells in the retina. It is also called neovascular AMD.
The small-molecule compound was developed by Yulia Komarova, Ph.D., associate professor of pharmacology and her colleagues at the University of Illinois at Chicago. It has the potential to reverse the damage from AMD and promote regenerative and healing processes.
“The idea was to develop something that can be more patient-friendly and doesn’t require a visit to the doctor’s office,” Komarova said in a press release.
The compound targets a protein called End Binding-3 (EB3) in endothelial cells, which line the inside of blood vessels. In a new study published in Cell Reports Medicine, Komarova and her colleagues looked at whether inhibiting EB3 function could stop the damaging leakage associated with wet AMD.
The team developed an inhibitor, which they call EBIN. They then tested its effectiveness in mice and non-human primates with wet AMD, finding that twice-daily treatment reduced eye damage within two to three weeks.
Researchers determined that the compound worked to reverse epigenetic changes in the eye, restoring normal gene expression. EBIN treatment was found to protect neovascular cells from the effects of environmental stress.
Because EBIN is a small molecule, it can be delivered by eyedrops. This would be an advantage over current therapies, which are delivered by injection. Current treatments for wet AMD focus on vascular endothelial growth factor (VEGF), which is believed to play a significant role in the abnormal formation of blood vessels in the macula. Current anti-VEGF therapies, however, require repeat treatments, with some dosed every month with intravitreal injections, where the therapy is delivered to the back of the eye.
Several anti-VEGF drugs are available, including Regeneron’s Eylea (aflibercept); Genentech’s Lucentis (ranibizumab); Genentech’s Vabysmo (faricimab-svoa); and Novartis’ Beovu (brolucizumab); and Genentech’s Susvimo (ranibizumab), which uses a refillable implant that delivers the medication continuously for up to six months.
Additionally, the anti-cancer drug Avastin (bevacizumab) is used off-label to treat wet AMD because it inhibits the growth of blood vessels to treat patients with colorectal and other cancers. The FDA, however, in August 2023 issued a complete response letter (CRL) for an ophthalmic formulation of bevacizumab because of issues related to quality, preapproval manufacturing inspections, and a lack of substantial evidence.
Anti-VEGF therapies work to inhibiting calcium signaling in response to inflammation. EBIN, the University of Illinois researchers found also prevents calcium signaling in endothelial cells, which is a key mechanism of inflammation. It works to prevent the destruction of endothelial cells because of inflammation induced by VEGF and other environmental stresses.