Building on previous research funded by JDRF, the organization has teamed with KalVista Pharmaceuticals, a company based in the United Kingdom, to continue the quest for therapies that will halt or delay the progression of diabetic eye disease.
Diabetic eye disease is the leading cause of blindness and impaired vision in people with type 1 diabetes (T1D). Diabetic retinopathy can occur after years of high blood-sugar levels cause the retina—the light-sensitive tissue at the back of the eye—to swell, making blood vessels in the eye leak. When fluid enters the macula—an area of the retina critical for sharp, straight-ahead vision—diabetic macular edema (DME) occurs and causes further swelling in the retina and impaired vision.
Supporting research to prevent or slow diabetic eye disease is a high priority for JDRF. The organization has a history of guiding innovative discoveries in the lab through the stages of clinical evaluation for effectiveness and safety and into development of therapies that help people whose vision is threatened by T1D.
We previously reported on JDRF-supported research on Lucentis, a treatment for DME already approved in the European Union in 2010 and Canada in 2011. Lucentis reduces vascular endothelial growth factor, which causes leakage in small blood vessels in the eyes of people with T1D. Many patients who used Lucentis had significantly improved vision, but not all respond to the drug, so it’s vital that the search for other treatments continues.
Previous studies funded by JDRF and led by a co-founder of KalVista, Edward Feener, Ph.D., associate professor of medicine at Harvard Medical School and Joslin Diabetes Center, were the first to detect high levels of an enzyme called plasma kallikrein—pronounced “ka-li-KREE-in,” or just “pK”—in the eyes of people with DME. Excessive amounts of pK cause inflammation, blood-vessel leakage, and thickening of the retina that damages vision.
Searching for a Therapy
In investigating new treatments for DME, KalVista will conduct preclinical trials to evaluate a group of possible therapies that utilize plasma kallikrein inhibitors to reduce the amount of pK in people with T1D. “Plasma kallikrein inhibitors target a known contributor to blood-vessel damage in the eye and have the potential to offer patients an effective treatment option,” says Andrew Crockett, CEO of KalVista. “Our preclinical studies for this potential therapy will begin this year, and we’re delighted that JDRF, the leading global organization committed to T1D research, has recognized the possibilities for our novel approach to treating DME.”
In teaming with KalVista, JDRF will provide up to $2.2 million in milestone-based funding and lend its vast research expertise. “Partnerships with companies such as KalVista are essential as we continue in our work to translate promising research into effective therapies for diabetic eye disease,” says Aaron Kowalski, Ph.D., assistant vice president of treat therapies at JDRF. “We’re in the preclinical stage of this research, but if the studies reveal one or more promising plasma kallikrein inhibitors that are ready for clinical development, we will have made a great stride toward providing a new treatment option for people with T1D.”
Why Target Plasma Kallikrein?
Like all enzymes in the body, plasma kallikrein (pK) acts as a catalyst to cause a specific biochemical reaction. Plasma kallikrein circulates in the blood and when it increases, it generates a potent, inflammatory hormone called bradykinin, which can cause blood vessels in the eye to enlarge and leak. High levels of bradykinin lead to high blood pressure and high blood sugar, which are major risk factors for the serious eye condition diabetic macular edema (DME).
Lowering pK levels may prove to be an effective therapy for all individuals affected by DME, and more importantly, may offer an alternative option to those individuals who do not respond to Lucentis. The KalVista Pharmaceuticals research supported by JDRF will test a group of potential plasma kallikrein inhibitors with the goal of finding an ideal candidate.