Enzyme Inhibitor Drug Offers Hope For Diabetes Sufferers

Diabetic patients are one step closer to avoiding related heart, kidney and eye complications, thanks to the combined efforts of researchers at the Joslin Diabetes Center and the Eli Lilly Pharmaceutical Company.

Dr. George L. King, professor of medicine at Harvard Medical School (HMS) and the Joslin Diabetes Center, has devoted more than 10 years of research to studying the effects of protein kinase C (PKC), a vital enzyme that regulates cells in the vascular system, on vascular complications in diabetics.

One of 12 known forms of PKC has been found to be "preferentially activated by diabetes and high glucose levels," King says, "[and] a high glucose level is thought to be the main cause of blood vessel problems in the heart, kidney and eye in diabetic patients."

A few years ago, King began to design an inhibitor to prevent this form of PKC from constricting blood flow and causing vessel leakage in the retina of the eye.

Along with fellow researchers Dr. Lloyd P. Aiello, assistant professor of ophthalmology at HMS and the Joslin Diabetes Center, and Dr. Szen Bursell, assistant professor of ophthalmology at HMS, the inhibitor, now known as LY333531, was created.

When tested on diabetic animals, the researchers found the inhibitor to be effective and non-toxic. These results were successful enough to warrant an initial ophthalmologic clinical trial, the results of which were first announced at last month's symposium honoring the 100th birthday of the Joslin Diabetes Center.

In its initial clinical trial, LY333531 helped the blood flowing through the retinas of diabetic patients remain at equivalent levels to those without diabetes, without creating any notable side effects.

The initial trial consisted of 29 individuals with types I and II diabetes, who were administered the oral drug for a month. Future trials will be conducted on a larger scale and will continue to study the effects of the inhibitor on blindness. If the next study, which consists of a thousand patients, proves effective, King and Aiello say they will send their findings to the FDA for approval.

"But it all depends on the effectiveness shown," cautions King.

After more studies are conducted on the effects of LY333531 on diabetic blindness, researchers hope to investigate the inhibitors' effectiveness on diabetic cardiovascular malfunctions.

"We have produced quite a bit of animal data to show [that] it's helpful to heart and diabetic kidney [disease,]" King said. "Hopefully, trials will start soon."