Researchers at the Medical University of South Carolina (MUSC) were recently awarded a $1.68 million grant from the National Institutes of Health (NIH) to investigate improved treatments for chronic pancreatitis, hopefully also leading the way toward finding a cure for type 1 diabetes. Chronic pancreatitis (chronic inflammation of the pancreas) can lead to permanent tissue damage, such as destruction of pancreas cells responsible for insulin production. The condition has been linked to diabetes development.
Dr. Hongjun Wang from MUSC’s Department of Surgery is the team’s leader, and their goal is to find ways to enhance the survival of islet graft (small groups of pancreatic cells that produce insulin) after cell transplantation in chronic pancreatitis patients.
The team previously conducted a smaller pilot study to assess the protective effects of a liver protein called Alpha 1 anti-trypsin (AAT ) in islet transplantation in mice models, using human islets collected from cadaveric donors. The researchers observed that the AAT added infusion prevented mice from developing diabetes and improved their liver implantation.
The study will analyze if humans can replicate the success of the mice pilot study, so the 5-year NIH grant will involve intravenous (IV) AAT infusion into patients who had their pancreas surgically removed. “The goal is to lessen the number of patients who are diabetic at the end of 1 year,” explained Dr. Wang in a MUSC press release.
Researchers remain uncertain of how the anti-inflammatory AAT properties work. “Through studies like this, the investigators seek to understand how AAT works in the body to lessen cellular stress,” said Dr. Wang. “AAT, most commonly used for the treatment of emphysema for more than 25 years, has an excellent safety record. The islet auto-transplantation 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,” added Dr. Wang. Chronic pancreatitis is usually caused by a pancreas gland inflammation, an organ connected to the intestine that is responsible for excreting enzymes that make it possible for us to digest what we eat. But these enzymes are inflammatory, if they come into contact with the body’s tissues. The pancreas gland is also responsible for secreting hormones into the blood stream; one of them is precisely insulin.
Damage to the pancreas gland can be caused by a number of different reasons, such as high levels of triglycerides, common drugs, and excessive alcohol intake. The canal leaving the gland can become damaged or blocked, causing pancreas enzymes to destroy the gland, resulting in a very painful condition with few therapeutic alternatives. One of the therapeutic options is the surgical removal of the pancreas, or a pancreatectomy. “But the surgery creates problems, too,” explained Dr. Wang. “It means that all of the patient’s islet cells also are removed, taking away the patient’s insulin and making the patient diabetic, which creates other lifelong complications.”
Dr. Wang is an islet cell transplantation expert. Islet cell transplantation is a technique based on the removal of the pancreas gland and separation of the different cell types. The cells are then isolated and injected back into the patient, where they migrate into the liver, and hopefully remain there to continue producing insulin.“In the best outcomes, the patient would not be diabetic at all,” said Dr. Wang.
The amount of surviving cells after pancreas removal determines the severity of a patient’s diabetes, but it is such a detailed and demanding procedure that it can only be performed at a very small number of specialty centers. Dr. Wang believes in the value of islet cell transplantation research at MUSC, and also in the level of expertise of her fellow clinicians, due to its National Pancreas Foundation center designation — one of the few centers focusing on a multidisciplinary approach to treat pancreatitis.
“This study is half basic science and half clinical. At MUSC, we have the some of the best pancreatic surgeons in the country, and if we have questions in the research environment, we can work directly with the surgeons to find solutions,” concluded Dr. Wang. “We are excited to be at the cutting edge of translating basic science research into clinical outcomes that will change the way we treat not only patients who suffer from chronic pancreatitis but eventually patients with type 1 diabetes, (…) Just imagine a day when people with type 1 diabetes no longer need to take their insulin. That’s the future. That’s the direction we are going.”