The United States Department of Defense has awarded a $1.27 million grant to Weill Cornell Medicine to develop treatment for proliferative vitreoretinopathy, a rare but devastating disease largely affecting military personnel who suffer traumatic eye injuries in combat. Under the three-year grant, the Weill Cornell Medicine investigators will test the safety and effectiveness of two newly developed antibodies to treat the disease.
Dr. Donald D’Amico
“The condition when fully developed can only be addressed with complex vitreoretinal surgery that may offer limited visual recovery; a preventative approach is not currently available and would be a major advance,” says Donald J. D’Amico, MD, Ophthalmologist-in-Chief, NewYork-Presbyterian/
“Proliferative vitreoretinopathy is a potentially blinding disease, and it is definitely worth trying to preserve vision, especially in people defending our country and in patients with other predisposing eye disorders,” says lead investigator Katherine A. Hajjar, MD, 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. Key collaborators include Dr. D’Amico, ophthalmologist Szilard Kiss, MD, and research associates Min Lucy Luo, PhD and Valentina Dallacasagrande, PhD.
Dr. Katherine Hajjar
“We are so pleased to partner with Dr. Hajjar on this most important research,” says Dr. D’Amico. “To develop a treatment that has the potential to halt the disease process of this catastrophic condition would be life-changing for patients.”
A major complication of rhegmatogenous retinal detachment, proliferative vitreoretinopathy (PVR) is characterized by the growth and contraction of cellular membranes within the vitreous cavity and on both sides of the retinal surface as well as intraretinal fibrosis. Some 200,000 people worldwide each year sustain a penetrating wound to the eye, the main risk factor for PVR. Its 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.
Unleashing the Potential of A2-Blocking Antibodies
The new project builds on Dr. Hajjar’s prior studies, also funded by the Department of Defense, that revealed that mice who lacked the gene for the protein annexin A2 – which enables cells from the retina to band together in response to an eye injury – were protected from developing PVR. Dr. Hajjar and her team now seek to 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.
“Our TDI partners are experts in making and characterizing the humanized antibodies we’re using in our animal models to make sure they are indeed reacting with the right protein in the right way,” says Dr. Hajjar. “If we find one that works well, we hope it can quickly be transferred to humans, which would dramatically shorten the drug development time.”
If their efforts succeed, Dr. Hajjar hopes to partner with a pharmaceutical or biotech company to bring their discovery to clinical trial within five years. In real-world use, the PVR treatment could be injected into a patient’s eye shortly after a traumatic eye injury. “At military conferences I’ve learned that they are looking for a treatment that could be administered in a field hospital minutes to hours after an injury,” says Dr. Hajjar. “I envision 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.”
Weill Cornell Medicine is one of only a few research centers focusing on PVR, notes Dr. Hajjar. “I believe we have a unique ability to partner with a drug development institute right here on our own premises. The whole process would not be possible without their participation.”
The new research might also influence treatment for conditions 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, which can be so disfiguring and demoralizing for patients,” says Dr. Hajjar. “These investigations are 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.”