Australian breakthrough brings a cure one step closer

Researchers at Melbourne's St Vincent' s Institute have found a way to completely prevent type 1 (also known as juvenile) diabetes in mice. The discovery could make islet transplantation - a promising cure for type 1 diabetes - more available to people with the disease.

What is an Islet Transplant?

A normal pancreas contains clusters of cells known as islets. Comprising about 1% of the total volume of the pancreas, islets contain beta cells, which produce insulin. In people with type 1 diabetes, the body's immune system malfunctions, creating inflammation as if it was responding to an invading infection. This destroys the islet cells, removing the body's ability to produce insulin.

Without insulin, glucose from food cannot enter the cells of the body. Instead it accumulates in the blood to high levels, which in turn damage the blood vessels and organs of the body. People with type 1 diabetes face a lifetime of insulin injections and a high risk of blindness, kidney disease, stroke, heart disease and amputation. The only way to cure diabetes in people who already have the disease, is to replace the destroyed beta cells or replace their function.

Whole-pancreas transplants have been successful for many years, restoring insulin production in people with advanced diabetes. However, it is a major operation and the significant risks associated with this procedure mean it is limited primarily to people who also require a kidney transplant.

Transplantation of islets has been investigated as an alternative to whole-pancreas transplants for three decades. Islet transplantation involves transplanting only the islet cells that contain the critical insulin-producing beta cells, removing the need for daily insulin injections. Compared to whole-pancreas transplantation, islet transplantation is a simpler and less invasive procedure.

Removing the Need for Immune-Suppression

Developments in islet transplantation over the last four years have increased the success rate of the procedure from 8% to over 80%. However, serious obstacles remain before islet transplantation can be considered as a true cure for diabetes and a procedure suitable for children.

In particular, the ongoing need for powerful immune-suppressant drugs is a major issue which prevents the young people usually affected by type 1 diabetes from benefiting from the procedure. These drugs are required to prevent rejection, but leave the patient vulnerable to infection.

"When you transplant anything into another person they will respond against it as something foreign," said St Vincent's Institute researcher Mark Chong, who presented the findings at the Immunology of Diabetes Society Meeting in Cambridge, UK. In the case of diabetes, they are not only rejecting the transplant, they may also be reacting as if it is their own cells."

SOCS1

Researchers have discovered that adding a molecule called 'Suppressor of Cytokine Signalling 1', or SOCS1, to insulin-producing islet cells before they are transplanted may do away with the need for these powerful immune-suppressant drugs.

"SOCS1 was discovered by Melbourne scientists several years ago," said Professor Tom Kay, Director of St Vincent's Institute. "The job of SOCS1 is to keep inflammation in check, turning it on and off as needed."

"SOCS1 is produced in every cell of the body including the pancreatic beta cell, which is the target of inflammation in diabetes," said Professor Kay. "Beta cells make SOCS1, but not enough to entirely protect itself. We thought that maybe if you added more SOCS1 to the beta cell, it would stop those cells becoming inflamed and being destroyed."

Using genetic technology, researchers stimulated 10 times the normal SOCS1 production in the pancreas of mice that had been bred to develop diabetes in their first four months of life. They found that SOCS1 shielded the beta cells and stopped all the mice from developing diabetes.

"It's the first time SOCS1 has been used to cure this model of diabetes," Professor Kay said.

The Next Step

St Vincent's Institute, which is establishing the first islet transplant program in Victoria, now aims to test SOCS1 on pancreatic islet cells from donated human organs. If laboratory testing is successful, SOCS1 enhanced islet transplants could be performed within five years.

Long-term drug research could also create products that activate SOCS1 production in the pancreas. Boosting SOCS1 production may also be beneficial in the treatment of other auto-immune diseases and a range of organ or tissue transplants.

JDRF Support

Professor Tom Kay has been the recipient of several JDRF grants, including a Career Development Award (US$496874). He currently receives a five year JDRF/NHMRC Special Program Grant (US$1,134,826) for his work in preventing the destruction of insulin producing cells.

For further information:

Karolyn Andrews, Media & PR Manager, JDRF
Ph. 02 9966 0400 (x203) or 0403 787 077 | email: kandrews@jdrf.org.au