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Drug prevents diabetes-related eye disease in rats

Monday, February 17, 2003

WASHINGTON -- A synthetic form of vitamin B1 that is used in Europe to treat nerve problems has been found to prevent the most common form of diabetes-related eye disease in rats.

Diabetic rats treated with benfotiamine for 36 weeks did not develop any of the retina damage found in a similar group of untreated rats, according to a research team led by Dr. Michael Brownlee of the Albert Einstein College of Medicine in New York.

Brownlee said he hopes to begin a clinical trial to determine whether a similar result would occur in humans once an effective dose for the drug in people is determined. That could happen as soon as a year, he said.

"We can't say it works in humans because there has never been a double-blind clinical study" of it, Brownlee said.

The new findings are published today in the online edition of the journal Nature Medicine.

In the United States, diabetes is the leading cause of blindness in people age 20 to 70. Diabetic retinopathy -- damage to the small blood cells in the retina -- is the most common problem. The American Diabetes Association estimates that between 12,000 and 24,000 people lose their sight each year because of diabetes.

In diabetics, excess sugar in the blood can damage some cells, especially those lining blood vessels, that are unable to block the sugar from entering. That sugar is burned for fuel by mitochondria, the energy engines of cells.

In cells that cannot regulate their amount of sugar, byproducts accumulate that can activate three different pathways of cell damage that can lead to blindness and other complications.

Brownlee's group focused on two compounds involved in this damage. Those compounds are affected by an enzyme called transketolase, which depends on thiamine -- also known as vitamin B1 -- for its activity.

The researchers sought to block the cell damage by using thiamine to boost the activity of transketolase, but this increased the enzyme activity only about 20 percent.

German researchers on the team suggested trying the synthetic thiamine form, benfotiamine, and it increased the enzyme activity by 300 percent to 400 percent, Brownlee said.

"So that was a stroke of luck," Brownlee said in a telephone interview. Benfotiamine blocked all three damage pathways by converting the damaging compounds into harmless chemicals.

While benfotiamine is a synthetic derivative of thiamine, it is different from that vitamin, Brownlee said. He cautioned diabetics that "going out to a health food store and buying a lot of thiamine is not going to help."

Dr. Francine Kaufman, president of the American Diabetes Association, said the findings are exciting because they show a way to block all three damage pathways in cells lining blood vessels.

There are other products in the pipeline dealing with one or another of the pathways but not all three, she said.

In addition, benfotiamine has been in use in Germany for years to treat painful types of nerve damage, including nerve damage caused by diabetes, and seems to have few side effects. Thus "it might not take forever to get into clinical trials," said Kaufman, a pediatric endocrinologist at Children's Hospital in Los Angeles.

"It's a big leap from animals to humans, but this is quite encouraging," she said.

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On the Net:

Nature Medicine: http://www.nature.com/nm


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