News Release

Jefferson researchers find that by blocking growth factor, diabetic kidney disease can be prevented in mice

Peer-Reviewed Publication

Thomas Jefferson University

Researchers at Jefferson Medical College and the University of Pennsylvania have successfully demonstrated how an antibody can block the effects of a growth factor in mice to prevent diabetic kidney disease. The antibody does not affect blood sugar levels or blood pressure.

Kumar Sharma, M.D., director of the Center for Diabetic Kidney Disease at Thomas Jefferson University Hospital in Philadelphia, Fuad N. Ziyadeh, M.D., of the University of Pennsylvania, and their colleagues found that treating mice with type 2 diabetes with an antibody for the transforming growth factor-beta (TGF-beta) protein, prevented kidney scarring and renal failure-indicators of diabetic kidney disease. Approximately 30 percent of African Americans and five to 10 percent of Caucasians who have type 2 diabetes develop kidney disease. Dr. Sharma says that this knowledge has the potential to be applied to humans. For human applications to be possible, researchers must develop antibodies that can be tolerated by humans.

They report their findings July 5 in the Proceedings of the National Academy of Sciences.

With type 2 diabetes, the body either makes too little insulin or cannot use the insulin it makes to change blood glucose to energy. Type 2 diabetes can usually be controlled through diet, medication or insulin.

"Results of this study build upon our recent findings that patients with diabetic kidney disease have an overproduction of TGF-beta in their kidneys," says Dr. Sharma, who is also associate professor of medicine at Jefferson Medical College of Thomas Jefferson University.

About 400 patients are seen annually at Jefferson's Center for Diabetic Kidney Disease. "Of these," Dr. Sharma says, "only those in the early stages of the disease will benefit from current treatment. The majority, who are in the advanced stages of diabetic kidney disease, go on to develop end-stage kidney disease requiring treatment with dialysis or a kidney transplant." Caring for patients with end-stage kidney disease costs approximately $7 billion annually in the United States.

In the current study, research was conducted on two strains of mice: one that develops type 2 diabetes spontaneously through a genetic mutation and nondiabetic mice from the same litter. At eight weeks, when the diabetic mice showed high blood sugar levels, they and the group of nondiabetic mice were injected three times a week for an additional eight weeks with a monoclonal antibody that can neutralize TGF-beta. A control group of both mice received a neutral antibody with no effect.

For the findings of this study to be applied to humans, the antibody must be made so that it can be tolerated by humans (humanized), Dr. Sharma says, a process several companies, including Genentech which supplied the antibodies in this study, are currently working on.

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Dr. Sharma and Tracy A. McGowan, M.D., assistant professor of medicine at Jefferson Medical College, are also initiating a separate study in patients to test whether a compound known as pirfenidone, an anti-fibrotic agent, can block the progression of diabetic kidney disease. This compound, which is provided by Marnac Inc. of Dallas, appears to work by blocking TGF-beta.

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