October 13, 2011

Grant funds new studies on debilitating diabetes conditions

Researchers Young-Sup Yoon and Xiaodong Cheng.

Patients with diabetes are frequently affected by peripheral arterial disease and diabetic neuropathy, but despite the increase in incidence of diabetes, no current treatments effectively treat these conditions, according to Young-Sup Yoon.

Yoon, director of stem cell biology and associate professor of medicine (cardiology) in Emory's School of Medicine, and Xiaodong Cheng, professor of biochemistry in the School of Medicine and a Georgia Research Alliance Eminent Scholar, will be researching these two complications in a new National Institutes of Health (NIH)-funded series of studies at the School of Medicine.

Yoon and Cheng are the principal investigators of a team working to re-program cells taken from the bone marrow or peripheral blood of patients with diabetes to treat neurovascular complications such as peripheral arterial disease and diabetic neuropathy.

Peripheral arterial disease and diabetic neuropathy are two of the most common and debilitating complications of diabetes.

Patients with peripheral arterial disease experience blocked arteries in the legs and feet, which can lead to leg amputation in advanced cases. Because advanced peripheral arterial disease in diabetes frequently affects small vessels, conventional intervention and surgical treatment are ineffective in many cases. 

Diabetic neuropathy, which damages the neural vasculature and neuronal cells, is the most common complication of diabetes, affecting 60 percent of patients.

Growing evidence has shown that cells taken from a patient's own bone marrow, called bone marrow-derived endothelial progenitor cells (EPCs), can be effective in treating various cardiovascular diseases and diabetic neuropathy by repairing blood vessels. Thus far, however, EPCs derived from diabetic patients have been only modestly effective for these autologous (self-directed) therapies.

The Emory research team, based on earlier findings, believes epigenetic changes in the EPCs of diabetic patients may be at fault. Epigenetic factors direct genes to be either expressed or silenced, but they don't affect the underlying DNA sequence of an organism. Epigenetic alterations in the chromatin of the EPCs of diabetic patients seem to be the culprit. Chromatin is the packaging mechanism for DNA in the nucleus of cells.

"We plan to investigate epigenetic chromatin changes in diabetic EPCs, and to reprogram or re-engineer these EPCs with small molecular epigenetic regulators and biomaterial to enhance or restore their function," Yoon explains. "Other research has shown the ability of small molecules to induce chromatin remodeling of affected genes and alter gene expression, and we believe this is a promising approach.

"Even after patients achieve glucose control, diabetes can lead to long-term complications," he says.

The research team will use animal models to test the therapeutic effects of the reprogrammed cells for peripheral arterial disease and diabetic neuropathy. The next step will be a pilot clinical trial in human patients with complications of diabetes.

The National Institute of Diabetes and Digestive and Kidney Diseases, part of the NIH, has awarded the research team — which includes investigators at Georgia Tech, University of Alabama and University of California at San Diego as well as at Emory — a $6.1 million grant.

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