Diabetic macular edema (DME) is a leading source of vision loss around the world, affecting about a fifth of people with long-term diabetes. Drugs that target a protein known as VEGF (vascular endothelial growth factor) inside the eye have greatly improved the treatment options in recent years, but only about half of DME patients are fully responsive to these new therapies.
Edward P. Feener, Ph.D., Investigator in the Section on Vascular Cell Biology and Director of the Proteomics Core at Joslin Diabetes Center and an Associate Professor of Medicine at Harvard Medical School.
Research in the lab of Edward P. Feener, Ph.D., Investigator in the Section on Vascular Cell Biology and Director of the Proteomics Core at Joslin Diabetes Center and an Associate Professor of Medicine at Harvard Medical School, now has shown that a substantial percentage of patients with DME do not have high levels of VEGF in the fluid inside their eyes but do have high levels of a protein called PKal (plasma kallikrein) and associated molecules that are key players in an inflammatory molecular pathway involved in the disease.
The scientists also have demonstrated in animals that the PKal molecular pathway can induce retinal edema through mechanisms that are independent of the VEGF pathway, which at normal levels helps to build and maintain blood vessels but at high concentrations can induce abnormal vessel growth and contribute to DME.
Outlined in a paper, the discoveries boost the evidence that agents targeting PKal eventually may be useful in treating DME that is not fully responsive to VEGF inhibitors.
In August 2014, KalVista Pharmaceuticals Ltd. launched an early phase clinical trial of a PKal inhibitor to treat DME, with Jennifer Sun, M.D., Ph.D., of Joslin