30-DEC-2015, MEDICAL UNIVERSITY OF SOUTH CAROLINA -- MUSC researchers received a $1.68 million National Institutes of Health grant to explore a better treatment for chronic pancreatitis, with the hopes that it also may shed light on a future cure for patients with type 1 diabetes.

Hongjun Wang, Ph.D., of the Medical University of South Carolina's Department of Surgery, is leading a collaborative team to study ways to increase the survival of the islet graft following islet cell transplantation for chronic pancreatitis patients. Islets are tiny clusters of cells in the pancreas that produce insulin.

Researchers in Wang's lab earlier piloted a smaller study looking at the protective effects of Alpha 1 anti-trypsin (AAT) in mice islet transplantation using human islets from cadaveric donors. The results showed that infusion with AAT prevented the mice from getting diabetes and improved liver implantation.
AAT is a protein made in the liver. Normally, the protein travels through the bloodstream, helping to protect the body's organs from the harmful effects of other proteins.

The five-year NIH grant involves infusing AAT into patients who have had their pancreas removed for one month by a weekly IV infusion. The study will examine whether humans will replicate the success seen in the mouse model. "The goal is to lessen the number of patients who are diabetic at the end of 1 year," Wang said.

How the anti-inflammatory properties of AAT work remains unknown. "Through studies like this, the investigators seek to understand how AAT works in the body to lessen cellular stress," she said.

"AAT, most commonly used for the treatment of emphysema for more than 25 years, has an excellent safety record," Wang said. "The islet autotransplantation model offers a unique opportunity to assess the direct effect of AAT on human islets in the absence of an immune response.

"While much of the work associated with AAT has been directed at lung and liver disease, it may help in the treatment of other diseases, including chronic pancreatitis, which can be incredibly painful," Wang said.

Chronic pancreatitis is caused by inflammation of the pancreas gland, an organ that has a duct connecting it to the intestine. The pancreas gland is responsible for excreting many of the enzymes that allow us to digest food. These enzymes are inflammatory if they get into the body's tissues. The pancreas gland also secretes hormones into the blood. The most important of these is insulin.

Inflammation and destruction of the pancreas gland is caused by a variety of conditions including some common drugs, high levels of triglycerides and too much alcohol. The duct that leaves the gland can become scarred and blocked and the pancreas enzymes can further destroy the gland. The result is a painful condition that has few cures.

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