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Synthetic thiamine derivative could help prevent diabetic retinopathy
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NEW YORK — A synthetic derivative of thiamine may be effective in preventing diabetic retinopathy, animal studies suggest. The drug blocks three of the four major biochemical pathways responsible for blood-vessel damage that causes serious diabetic complications, according to research done here.
Benfotiamine, a synthetic derivative of vitamin B1, has been available for more than a decade in Germany, where it is used for the treatment of diabetic neuropathy, sciatica and other painful nerve conditions.
Michael Brownlee, MD, and colleagues here with the Albert Einstein College of Medicine treated diabetic rats with benfotiamine for 36 weeks. A control group of rats with diabetes was left untreated. Upon conclusion of the study, the rats being treated with benfotiamine had not developed any of the retinal damage seen in the non-treated group.
In people with diabetes, endothelial cells that line the arteries and the capillaries of the retina and kidney are unable to regulate glucose. Dr. Brownlee’s group focused on two glucose-derived intermediates that activate three of the damaging biochemical pathways. They hypothesized that by boosting transketolase activity, they might be able to reverse the pathway (in essence, making the damaging pathways harmless). Preliminary studies with standard thiamine boosted transketolase’s activity by only 20%. Benfotiamine, a fat-soluble thiamine derivative, was more potent.
“By pure serendipity, it turned out that benfortiamine boosted the activity of the enzyme transketolase by 300% to 400%, something we could never have predicted based on benfotiamine’s chemical structure,” Dr. Brownlee said.
A chemical analysis of the diabetic rats treated with benfotiamine showed three of the biochemical pathways had been “normalized” to the point where the retinas were biochemically identical to those of normal rats. According to Dr. Brownlee, benfotiamine prevented the onset of diabetic retinopathy, since a microscopic examination showed the retinas of the rats that had been given the derivative were free of vascular damage.
Dr. Brownlee said he plans to submit an Investigational new drug application to the Food and Drug Administration, and he is fairly confident the drug will have a clean safety profile, based on its use in Germany.
Dr. Brownlee’s study will be published in the Feb. 24 issue of the journal Nature Medicine.