Bascom Palmer’s Dr. Wei Li Awarded $9.12 Million NEI Grant
Wei Li, Ph.D., from Bascom Palmer Eye Institute at the University of Miami Miller School of Medicine, has been awarded a five-year $9.12 million R24 grant from the National Eye Institute (NEI) to develop a new drug that would protect infants from potentially blinding eye disorders due to retinopathy of prematurity (ROP).
Wei Li, Ph.D.
ROP primarily affects premature infants weighing about 2 ¾ pounds, or born before 31 weeks of gestation. About 28,000 infants in the United States each year fall into this category. Of these, about 14,000 to 16,000 are affected by some degree of ROP in which disrupted development of the blood vessels in the eye spreads throughout the retina, causing scarring and bleeding. While most of these children do not need treatment, about 1,100 to 1,500 infants annually develop ROP that requires medical treatment, while 400 to 600 infants each year in the U.S. become legally blind from the disease.
The clinical symptom of ROP is characterized by abnormal and disorganized growth of retinal blood vessels, called pathological angiogenesis, which may cause bleeding, retinal detachment and even blindness. On the other hand, preterm infants require normal and organized blood vessel formation or physiological angiogenesis to support retinal development. Several drugs, called angiogenesis inhibitors or blockers, have been developed and approved to treat angiogenesis diseases in adult retina. However, compared with adults with fully developed retina, ROP infants with developing retina and blood vessels are particularly susceptible to side effects caused by non-selective angiogenesis inhibitors. As a result, there is currently no FDA-approved drug therapy for ROP, which is treated with laser therapy to “burn away” the periphery of the retina. This therapy destroys the peripheral retina to save the central retina with limited efficacy and does not address the underlying cause of abnormal retinal blood vessel growth.
Dr. Li invented a new technology to systematically screen for disease-restricted or selective drug targets. Using this technology, he discovered a protein called secretogranin III (Scg3) that selectively exacerbates pathological angiogenesis in ROP but does not regulate physiological angiogenesis in the developing retina of preterm infants.
He generated a therapeutic antibody to specifically inhibit Scg3 function. This anti-Scg3 antibody is a prototype of the next-generation disease-selective angiogenesis blockers that can selectively inhibit pathological but not physiological angiogenesis. As a result, the antibody will alleviate ROP but not cause side effects on normal developing retina. Dr. Li further engineered this antibody to generate related “humanized” antibody that is suitable for disease therapy in humans.
This NIH R24 grant will support the work to further develop this humanized antibody for targeted therapy of ROP with minimal side effects. In the next five years, Dr. Li will perform additional studies to analyze the therapeutic efficacy and safety of this humanized antibody in various experimental models of ROP by strictly following FDA guidelines. At the end of the project, he will summarize all the results in an application to the FDA for clinical trials.
Much of Dr. Li’s work takes place within Bascom Palmer’s Ocular Vascular Disease Laboratory. A major focus of the lab is to develop disease-selective angiogenesis blockers for eye diseases, including diabetic macular edema, proliferative diabetic retinopathy, wet age-related macular degeneration, cancers of the eye and retinopathy of prematurity.
“Results from this study will be significant because anti-Scg3 antibody has the potential to become the first FDA-approved drug for ROP therapy,” said Vittorio Porciatti, D.Sc., the James L. Knight Professor of Ophthalmology and director of research at Bascom Palmer Eye Institute.
NEI at the National Institutes of Health usually funds only one or two R24 grants each year to support the development of novel therapies and devices for the treatment of eye diseases. Typically, an R24 grant requires a multidisciplinary team of scientists and clinicians to focus on generating preclinical data that will lead to the development of new drugs or medical devices for eye disease therapy.
Dr. Li, a research associate professor of ophthalmology, assembled an interdisciplinary team with more than 10 scientists and clinicians for this R24 project. Keith A. Webster, Ph.D., professor of molecular and cellular pharmacology and the Walter G. Ross Distinguished Chair in Vascular Biology at the University of Miami Miller School of Medicine, is the co-principal investigator for this research project. Audina M. Berrocal, professor of clinical ophthalmology, a retinal specialist with expertise in retinopathy of prematurity at Bascom Palmer, joins this project as a co-investigator.
About Bascom Palmer Eye Institute
Bascom Palmer Eye Institute, part of University of Miami Hospital and Clinics, is ranked the nation’s best in ophthalmology by U.S. News & World Report, an honor it has received for the 17th time, and by Ophthalmology Times. In addition to its international reputation as one of the premier providers of eye care in the world, Bascom Palmer is the largest ophthalmic care, research and educational facility in the southeastern United States. Each year, more than 260,000 patients with nearly every ophthalmic condition are treated, and more than 16,000 surgeries are performed. With five patient care facilities in Florida (Miami, Palm Beach Gardens, Naples, Plantation, and Coral Gables), the Institute serves as the Department of Ophthalmology for the University of Miami Miller School of Medicine and is directed by Eduardo C. Alfonso, M.D. Bascom Palmer faculty members also staff the Miami and West Palm Beach Veterans Affairs Medical Centers, Jackson Memorial Hospital and Nicklaus Children’s Hospital. The sponsored research enterprise at Bascom Palmer has grown from $3.8 million in 2004 to $16 million in 2018.
Tags: Bascom Palmer Eye Institute, Dr. Wei Li, National Eye Institute, retinopathy of prematurity