By Kim Coghill

Washington Editor

Dynamis Therapeutics said it has discovered an enzyme that could be responsible for diabetic kidney disease and also has developed a small-molecule drug that could help reduce the incidence of some related complications.

The enzyme, Amadorase, is responsible for the formation of 3-deoxyglucosone (3DG) in the kidneys of diabetic patients. 3DG, a reactive molecule, causes proteins to cross-link, lose function and block arteries, and it is a proven factor in the development of advanced glycation end products (AGEs), a leading cause of diabetic kidney disease.

Dynamis' small-molecule drug, DYN 12, reduced 3DG levels in diabetic rats.

"No one believed that there was an enzyme that was causing production of 3DG, so we have had no support and we have done this on our own," said Annette Tobia, president, CEO and co-founder of Wyndmoor, Pa.-based Dynamis. "I am furious and thrilled at the same time. I would like to say that not only did we discover the enzyme, but we discovered the whole metabolic pathway."

Tobia said 3DG is carried in the blood and causes damage wherever it goes. A drug targeting 3DG could prevent diabetic complications including kidney disease, hardening of the arteries and miscarriages of diabetic women.

"This drug could conceivably be a $2 billion drug the first year because anyone with diabetes should be on it," Tobia said.

To that end, Dynamis, formed in 1997, is looking for a corporate partner to develop drugs and fund studies that prove diabetic-related kidney and circulatory problems can be prevented by inhibiting 3DG.

Truman Brown, co-founder of Dynamis and chairman of its scientific advisory board, said in a prepared statement, "The dramatic lowering of the levels of 3DG in both urine and plasma confirms that the inhibition of Amadorase represents a totally new and novel approach to combating diabetic complications. This significant scientific discovery brings us much closer to reaching our goal of preventing the long-term complications of diabetes in a safer manner than any other approach. We use low concentrations of DYN 12. The drug is concentrated in the kidney, the target organ, and does not appear to concentrate elsewhere, minimizing the potential for adverse side effects."

Dynamis was founded on technology from the Fox Chase Cancer Center in Philadelphia, where research on the Amadorase inhibitor was conducted. Tobia said Dynamis' goal is to develop products for which 3DG is the culprit.

Diabetes impacts an estimated 16 million people in the U.S. alone, according to the American Diabetes Association. An estimated 30 percent to 40 percent of those with Type I diabetes and 10 percent to 15 percent of those with Type II diabetes are likely to develop kidney disease, the leading cause of end-stage renal failure, with an associated cost of more than $5 billion annually. n

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