Diabetes Drug Found Safe

Shows promise for preventing blindness

By William J. Cromie

Gazette Staff

A promising drug to prevent blindness associated with diabetes has passed its first safety test. Loss of sight due to diabetes causes 12,000 to 24,000 new cases of blindness each year in the United States, where it is the leading cause of adult blindness.

Researchers announced that the new oral drug, tested on 29 people with both adult-onset and juvenile diabetes, successfully treated blood-flow problems that occur in the early stages of diabetic eye disease.

"The findings support proceeding with larger trials that already are being performed at more than 30 sites throughout the world," said Lloyd P. Aiello, assistant professor of ophthalmology at the Medical School. If these trials verify the first results, the drug could benefit an estimated 16 million people in the United States and millions more worldwide who have diabetes.

The drug, called LY333531, is being developed by Aiello and his colleagues at Joslin Diabetes Center, a Harvard-affiliated teaching and research hospital in Boston.

When given to diabetic rats, LY333531 eliminated the type of blood vessel changes that lead to both blindness and kidney damage brought on by the disease. All of the people who participated in the safety trials had such changes in their eyes.

Such changes include slowing of blood flow through small blood vessels that feed the eye, and leakage from vessels in the retina, the screen at the back of the eye where images of the world are projected.

These abnormalities are linked to an oversupply of glucose, a blood sugar vital for supplying the body with energy. Diabetics lack enough of the hormone insulin to get the glucose into cells that need it. As the oversupply of glucose rises to dangerous levels in the blood, so does the activity of a protein called kinase C beta. LY333531 protects the eyes by blocking the action of this protein.

The Joslin scientists did the safety tests to determine if such blockage leads to unforeseen side effects. Apparently, it does not.

"The data indicate that LY333531 is safe and well-tolerated over a period of one month," Aiello noted. "The ability of the substance to prevent or reverse [blood-vessel] dysfunction in the retina . . . suggests that the drug may eventually prove to be effective. However, longer studies with more patients must be done to determine if the drug actually reduces vision loss.

"The potential applications for this finding are sizable," Aiello continued. "LY333531 represents a new class of drugs that may be able to prevent many complications in diabetic patients, such as those observed in the eye, kidney, nerves, and heart."

Other researchers at the conference where Aiello announced his results reported that LY333531, given with vitamin E, improved blood flow to nerves in diabetic rats.

Also, protein kinase beta C has been implicated in many other diseases. Finding the first compound that blocks its activity might someday lead to new treatments for arthritis, heart disease, cancer, and Alzheimer's disease.