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2005 research review > Drugs to Treat Complications

Drugs to Treat Complications
Cure Therapeutic: Creating Novel Ways to Predict, Prevent, and Treat Complications

During FY2005, several promising drugs for treatment of diabetic complications moved closer to the marketplace, while discovery research uncovered important new therapeutic targets.

Michael Brownlee, M.D.

Michael Brownlee, M.D., director of the JDRF International Center for Diabetic Complications at Albert Einstein College of Medicine in New York, investigated therapies that could block pathways by which high blood sugar damages cells and produces diabetic complications. A clinical study is testing benfotiamine, a synthetic derivative of the dietary supplement thiamine (vitamin B1) that appears to stop high glucose from damaging blood vessels. Benfotiamine has already been prescribed for more than a decade in Germany to treat sciatica and other nerve problems; if found effective against diabetes complications, the drug could get approval from the FDA faster than most compounds.

Another JDRF trial, about to end, tested the effectiveness of a drug, ranibizumab, against diabetic macular edema, a major complication that can lead to vision loss. Ranibizumab blocks a natural protein in the body called vascular endothelial growth factor, which is produced in excessive amounts in people with diabetes and causes leakage in the tiny blood vessels of the eye. This summer, the biotechnology company Genentech reported very favorable results from a large Phase III trial testing the drug (under the brand name Lucentis) for a similar condition, age-related macular degeneration. Results from the JDRF trial, conducted by researchers led by Quan Dong Nguyen, M.D., M.S., at the Wilmer Eye Institute at Johns Hopkins University, are expected soon.

Another trial is investigating whether a "cocktail" of antioxidant compounds will slow or prevent complications. At the JDRF Center for the Study of Complications of Diabetes at the University of Michigan, Eva Feldman, M.D., Ph.D., tested the therapeutic effects of three compounds—alpha lipoic acid, nicotinamide, and allopurinal—on the development of diabetes-related autonomic neuropathy. Since each compound affects a different segment of the damaging oxidative pathway, the trial is testing the efficacy of the compounds combined. Some of the patients have now completed the two-year Phase II study, and many more will reach the two-year mark within six months.

JDRF-supported basic research has also revealed promising new avenues for developing potential diabetes drugs. In January, JDRF-funded scientists at the University of Florida, led by Edward Scott, Ph.D., prevented retinopathy by injecting an antibody to block the action of a protein called SDF-1. The study was the first to present a solid link between SDF-1 (stromal cell-derived factor-1) and diabetic retinopathy, caused by rampant growth of blood vessels in the retina. This year, the antibody began testing in monkeys, and, if successful, will proceed to human clinical trials. This strategy could help millions of people with diabetes avoid the complications of retinopathy, the leading cause of adult blindness in the U.S.

Researchers also discovered that a naturally occurring byproduct of glucose, pyruvate, may protect against hypoglycemic brain damage. In May, JDRF-funded researcher Raymond Swanson, M.D., at the San Francisco Veterans Affairs Medical Center and the University of California, San Francisco reported that pyruvate therapy in animal studies prevented brain damage and subsequent learning and memory impairment far better than treatment with glucose alone. If pyruvate is found to have the same effect in humans, it could provide an important safeguard against brain cell damage caused by severe hypoglycemia. Pyruvate therapy may advance quickly to the clinical level because the substance naturally occurs in the body and, therefore, should not pose any long-term risks.

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