Weill Cornell Medicine has received a $1.27 million grant from the United States Department of Defense (DoD) to develop treatment for a rare but devastating eye condition largely affecting military personnel who suffer traumatic eye injuries in combat.
Under the three-year grant, investigators will test the safety and effectiveness of two newly developed antibodies to treat proliferative vitreoretinopathy, or PVR. Currently not treatable or preventable, PVR occurs when cells inside the eye bunch into a scar-like ball after a penetrating eye injury.
This is a potentially blinding disease and it's definitely worth trying to preserve vision, especially in people defending our country and in patients with other predisposing eye disorders."
Dr. Katherine Hajjar, lead investigator, the Brine Family Professor of Cell and Developmental Biology and a professor and vice chair for research in the Department of Pediatrics at Weill Cornell Medicine
About 200,000 people worldwide each year sustain a penetrating wound to the eye, the main risk factor for PVR. It can also occur in some who undergo complex eye surgeries or experience a detached retina. The condition's prevalence has risen among military personnel with the increasing use of explosive devices in modern combat and occurs in nearly half of those sustaining a penetrating eye wound.
The new project builds on Dr. Hajjar's prior findings, also funded by the DoD, revealing that mice who lacked the gene for a protein called annexin A2 - which enables cells from the retina to bunch up in response to eye injury - were protected from developing PVR.
Also using animal models, her team will now determine whether injecting A2-blocking antibodies into an injured eye can prevent PVR. The antibodies were developed by the Tri-Institutional Therapeutics Discovery Institute (TDI), a collaboration among Weill Cornell Medicine, Memorial Sloan Kettering Cancer Center and The Rockefeller University that is designed to expedite early-stage small molecule and antibody drug discovery into novel treatments for patients.
Other key collaborators and consultants include Weill Cornell research associates Drs. Min "Lucy" Luo and Valentina Dallacasagrande, lab supervisor Dena Almeida, professor and chair of ophthalmology Dr. Donald D'Amico and ophthalmologist Dr. Szilard Kiss.
"It has been a really interesting partnership with the TDI because they're experts in making and characterizing the humanized antibodies we're using to make sure they're indeed reacting with the right protein in the right way," said Dr. Hajjar, who is also senior associate dean for faculty at Weill Cornell Medicine. "If we find one that works well, we hope it can quickly be transferred to humans, so that would dramatically shorten the drug development time."
If the effort succeeds, Dr. Hajjar hopes to partner with a pharmaceutical or biotech company to conduct clinical trials in people within five years. In real-world use, the PVR treatment could be injected into a patient's eye shortly after a traumatic eye injury.
"I've been to military conferences, where I learned they're looking for something that could be administered in a field hospital minutes to hours after injury," Dr. Hajjar said. "What I envision is vials or pre-measured syringes of this material that a medic could inject into an injured eye even before the healing process has a chance to start, which would prevent scar tissue formation."
The project sets Weill Cornell Medicine apart as one of few research efforts focusing on PVR, Dr. Hajjar noted. "I can probably count on one hand the number of institutions doing something like this, and I think we have a unique ability to partner with a drug development institute right on our own premises," she said. "The whole process wouldn't be possible without their partnership."
As a "baby doctor" whose attention accidentally turned toward PVR after her lab experiments with the A2 protein, Dr. Hajjar said the new research might also produce revelations about treating conditions far beyond the eyes.
"A number of disorders involve a healing process that's gone off the rails, including pulmonary and kidney fibrosis and keloid scarring in the skin, which can be disfiguring and demoralizing for patients," she said. "This research is teaching us something about how wounds heal at a very basic level that might have a broad impact in treating other conditions that are applicable to children as well as adults."