Newswise — BOSTON – (September 10, 2014) – George King, M.D., Chief Scientific Officer and Senior Vice President of Joslin Diabetes Center and Professor of Medicine at Harvard Medical School, and Lloyd Paul Aiello, M.D., Ph.D., Director of the Beetham Eye Institute (BEI) and Professor of Ophthalmology at Harvard Medical School, were among seven individuals, including colleagues from Massachusetts Eye and Ear Infirmary, Genentech and UC San Diego, to receive the 2014 Antonio Champalimaud Vision Award for their contributions toward the discovery of treatments inhibiting vascular endothelial growth factor (VEGF) for ocular diseases. Drs. King and Aiello performed pivotal work in this area regarding the retinal diseases of proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME).
As the world’s largest award for vision research, the Champalimaud Award is presented to active researchers involved in basic or clinical research that has led to a major breakthrough in the understanding and preservation of vision. The award was presented to both Joslin researchers and their colleagues during a ceremony at the headquarters of the Champalimaud Foundation in Lisbon, Portugal.
“All of the award recipients, and myself in particular, are thrilled to be recognized with this honor,” said Dr. Aiello. “To be recognized as a part of such a distinguished group, which has contributed to this unique and highly successful effort over the last two decades, is a tremendous source of pride and inspiration for me.”
Dr. King echoed Dr. Aiello’s sentiments, “It’s always an honor to receive an award, especially an award of this stature, but I think it’s important to note that this research would have not been possible without the unique environment that exists here at Joslin.”
While Drs. King and Aiello’s search for anti-VEGF treatments spanned across almost two decades, the significant risk that eye complications pose to people with diabetes dates back much further to the introduction of insulin, which prolonged the lives of those living with the disease. By the 1960s, with diabetic patients living longer, diabetic eye disease grew to impact a large portion of the diabetes population, eventually threatening more than half of diabetic patients with the possibility of significant irreversible visual loss.
Changes to the retina called diabetic retinopathy will eventually affect nearly all persons with diabetes. The visual threat from this condition arises from two conditions. One is termed diabetic macular edema, which is caused by increased leakage of the small blood vessels in the back of the eye. When these blood vessels leak, the retina in the back of the eye swells and makes it difficult for the eye to receive light correctly. After this occurs, a patient’s vision becomes blurry and distorted. Treatments blocking VEGF have become the definitive initial choice for treating people with this condition once it affects their central vision.
As a patient’s diabetic retinopathy worsens, they may develop proliferative diabetic retinopathy where the blood vessels in their eyes grow in a disorganized manner. This can lead to bleeding and scarring of the blood vessels, reduced vision and ultimately destruction of the retina. Within the next year there will be information from clinical trials as to whether VEGF inhibitors can successfully treat this condition as well.
“One of the greatest fears of diabetic patients is to lose their eye sight because that has an immediate impact on everything they do,” said Dr. King.
The first widely effective treatment for diabetic retinopathy, panretinal photocoagulation laser therapy, was pioneered by William P. Beetham, M.D., and Lloyd M. Aiello, M.D. at Joslin in the 1960s. This therapy was immensely helpful in decreasing blindness for diabetic patients, but this success was accompanied by serious side effects. The destructive nature of laser therapy often reduced the ability of patients to see well during periods of limited light, such as at dusk or dawn, and also constricted their peripheral vision.
Prior to the discovery of VEGF, ophthalmologists and researchers hunted for “Factor X,” which they suspected was made within the eye and caused blood vessels to grow and leak in places they were not supposed to, leading to diabetic eye disease.
In the 1990s, Dr. Napoleone Ferrara, of Genentech, cloned the VEGF molecule, which was found to be responsible for triggering blood vessels to grow and leak. Upon learning of Dr. Ferrara’s discovery and subsequent discoveries regarding VEGF in the field of cancer, Drs. King and Aiello hypothesized that VEGF could be the “Factor X” causing high rates of eye disease in patients with diabetes.
“The studies suggested that VEGF had all of the required characteristics to mediate the retinal complications caused by diabetes,” explained Dr. Aiello. “Dr. King and I quickly found that this molecule had very potent effects on cells in the eye, and readily caused them to both grow and leak.”
It became apparent that VEGF might fulfill the three main criteria expected of “Factor X”: it was made in the eye, the presence of the molecule increased when the eye had lower levels of oxygen due to diabetic eye disease and it affected the cells in the retina by making them grow and leak.
These criteria were confirmed by work from both the basic research bench and the clinical research bedside. Studies utilizing eye fluids from patients with varying severities of diabetic and other eye diseases allowed Drs. King and Aiello to demonstrate that high levels of VEGF corresponded with worse eye conditions, and furthermore that it was the VEGF itself within these eye samples that was causing blood vessel growth and leakage. The studies were published in the New England Journal of Medicine in 1994.
“As soon as we had a good idea that VEGF was causing complications in the eye, the obvious next step was to try and find something that could block this factor,” said Dr. Aiello. “And if you could block this factor in the eye, then presumably this could be an effective treatment for complications of diabetic retinopathy.”
Drs. King and Aiello collaborated with Dr. Ferrara, who was at Genentech, and several other groups to examine possible VEGF inhibitors. The effort of many individuals eventually proved the benefit of VEGF blockade and resulted in FDA approval of VEGF inhibitors for several forms of ocular disease.
“Being able to bridge basic research with clinical and translational research was important here,” explained Dr. King. “The discovery of anti-VEGF treatments would have not been possible without all of the aforementioned factors, and we wouldn’t have been able to translate our findings into treatments for patients without all of the resources from my lab, Dr. Aiello’s connections to an extensive network of ophthalmologists and collaborations with Dr. Ferrara.”
According to Dr. Aiello, anti-VEGF treatments proved to be approximately twice as effective in improving vision and nearly three times more effective in preventing vision loss from diabetic macular edema than laser treatments. “As a result, now when most patients are identified for the first time with leakage in the center of their retina with associated loss of vision, the first line of treatment is a VEGF inhibitor therapy,” he said. “This has been a hugely beneficial advance because many of our patients regained much of their vision and very few lose any of their vision.”
Drs. King and Aiello are part of a group of seven researchers, including Napoleone Ferrara, M.D., Professor and Senior Deputy Director for Basic Sciences at University of California, San Diego Moores Cancer Center, Joan Miller, M.D., Chief and Chair of Department of Ophthalmology at Massachusetts Eye and Ear, Evangelos S. Gragoudas, M.D., Director of the Retina Service in the Ophthalmology Department at Massachusetts General Hospital, Patricia A. D'Amore, Ph.D., M.B.A., F.A.R.V.O., Director of the Howe Laboratoy at Mass. Eye and Ear as well as the Director of Research, Senior Scientist and the Ankeny Scholar of Retinal Molecular Biology at Schepens and Anthony P. Adamis, M.D., Vice President and Global Head Ophthalmology at Genentech, Inc., who are also receiving this award.
The prize award for the 2014 Antonio Champalimaud Vision Award is 1 million Euros (nearly $1.3 million) and will be distributed evenly among the recipients to further research into the preservation of vision.
“These awards help encourage us to develop new projects that will further our understanding and treatment of diabetes and its complications,” Dr. King added.
About Joslin Diabetes Center
Joslin Diabetes Center, based in Boston, Massachusetts, undertakes diabetes research, clinical care, education and health and wellness programs on a global scale. Joslin is dedicated to ensuring that people with diabetes live long, healthy lives and offers real progress in preventing and curing diabetes. Joslin is an independent, nonprofit institution affiliated with Harvard Medical School, and is recognized worldwide for driving innovative solutions in diabetes prevention, research, education, and care.
Our mission is to prevent, treat and cure diabetes. Our vision is a world free of diabetes and its complications. For more information, visit www.joslin.org.
About Joslin Research
Joslin Research comprises the most comprehensive and productive effort in diabetes research under one roof anywhere in the world. With 30‐plus faculty‐level investigators, Joslin researchers focus on unraveling the biological, biochemical and genetic processes that underlie the development of type 1 and type 2 diabetes and related complications.
Joslin research is highly innovative and imaginative, employing the newest tools in genetics, genomics and proteomics to identify abnormalities that may play a role in the development of diabetes and its complications. Joslin Clinic patients, and others with diabetes, have the option of participating in clinical trials at Joslin to help translate basic research into treatment innovations.
Joslin has one of the largest diabetes training programs in the world, educating 150 M.D. and Ph.D. researchers each year, many of whom go on to head diabetes initiatives at leading institutions all over the globe. For more information, visit www.joslinresearch.org.###
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