What is xenotransplantation?

For type 1 diabetes, xenotransplantation involves taking insulin-producing islets from animals —in this case, pigs—and transplanting them into people. Pigs are considered the best species for xenotransplantation because pig organs are similar in size and physiology to human organs and pig insulin has been shown to work effectively in humans.

Earlier this year, the Australian government’s National Health and Medical Research Council lifted a moratorium on the clinical use of xenotransplantation. The ruling came after five years of research into the possible side effects of the technique, particularly the potential transmission of disease from animals to humans. It concluded that xenotransplantation research can proceed, given that researchers adhere to strict guidelines, and that the associated risks with xenotransplantation are minimal and acceptable given the potential benefits.

How is xenotransplantation different from human islet transplantation?

Researchers and clinicians have used human islet cell transplantation to treat type 1 diabetes for over a decade. Some countries now fund the procedure as a standard treatment for people living with serious hypoglycemic unawareness.

The two main challenges for effective islet cell replacement in people with type 1 diabetes are the supply of cells available for transplant, and the need to suppress the body’s immune system.

The use of islet encapsulation technology, in combination with xenotransplantation techniques or stem cell technology, could help overcome the obstacles to effective human islet cell replacement.

Who is Living Cell Technologies?

Living Cell Technologies (LCT) is an Australian publicly-listed company working to develop and market the use of pig cells as treatment for human disease.

What research are they doing into type 1 diabetes

LCT has recently started human clinical trials in New Zealand to test one of their products as a treatment for type 1 diabetes. Called Diabecell®, this product comprises encapsulated, insulin-producing islet cells taken from specially bred pigs.

The pigs used for transplantation in the LCT study are grown and harvested in optimal conditions, and their health status is closely monitored, reducing the safety concerns. Viruses from pig cells have not been shown to be capable of passing to humans during this type of xenotransplantation.

How far has the research of LCT progressed?

Research into this product is still in relatively early stages. One initial clinical trial has been completed in Russia and a new trial is currently underway in New Zealand. These trials, consisting of 8 people each, have been primarily designed to provide initial data on the safety of the treatment on adults living with type 1 diabetes and hypoglycemic unawareness.

The trials will also provide preliminary data on clinical outcomes to inform the larger scale trials required to fully test treatment effectiveness. Results and analysis from the initial clinical trial have yet to be published in the scientific literature.

How is JDRF involved?

JDRF has provided funding support for the second stage of the NZ trial to test the safety and effectiveness of Diabecell® when given in higher doses. Four patients will receive this higher dosage and results will be compared to those who received the lower doses. This trial is expected to be completed in 2011.

When will the treatment be available for people with type 1 diabetes?

The technique is currently only approved for clinical testing purposes in Russia and New Zealand. As with all new medial techniques, extensive research must be completed to ensure maximum safety for treatment recipients and also to establish standard protocols for use before being made widely available.

It is too early to tell if and when this product will be commercially available as a treatment for type 1 diabetes.

Is JDRF funding any other projects involving xenotransplantation or islet encapsulation?

Yes. Islet encapsulation and xenotransplantation are important areas of research for JDRF as part of the beta cell therapies program. Over the past five years, JDRF has invested US$13 million into xenotransplantation research, and approximately US$8 million into encapsulation research worldwide.

In Australia, JDRF currently supports three research programs into the use of pig islets as therapy for type 1 diabetes.

The JDRF funding for Living Cell Technologies was provided through the international Industry Discovery and Development Partnership Program, designed to accelerate the discovery, development, and commercialization of disease-modifying therapeutics.

The trial, being conducted in New Zealand by Living Cell Technologies, involves eight adult patients with established type 1 diabetes and hypoglycemia unawareness – a constant inability to sense when blood glucose levels are dropping dangerously low.

Each patient has been surgically implanted with insulin-producing cells taken from specially bred pigs in a technique known as xenotransplantation – the transplantation of animal organs or tissues into humans to cure or treat health conditions.

Xenotransplantation is a growing field of interest for researchers as the use of animal tissues will circumvent the current shortage of human organ donors. It is also controversial in that some scientists believe undetected animal diseases could be transferred to humans.

The pig islet cells used in this trial were taken from a special herd of pigs that live on a remote island off New Zealand. The isolation of the colony has meant they have been theoretically untouched by the diseases that affect mainland pig herds.

The islet cells were also encapsulated in a special new substance made from seaweed – thus protecting the cells from immune attack whilst allowing the appropriate amount of insulin to be released effectively.

Living Cell Technologies scientists believe that using this technique will result in the transplanted cells will be able to safely effectively produce insulin and help control blood glucose levels without needing the harmful life-long regime of immune-suppression drugs that all organ transplant patients currently require.

Early results from the trial have shown that the implants do have an impact with one of the recipients reporting significantly reduced hypoglycemia unawareness.

Whilst xenotransplantation is banned in a number of countries, the New Zealand government has provided special dispensation for this trial to go ahead. The Australian National Health and Research Council has recently overturned a moratorium on animal-to-human transplants but guidelines are yet to be constructed to ensure any local trials are ethically and scientifically sound.

JDRF provides industry partnership funding to a number of large and small companies around the world to advance promising research into a cure for type 1 diabetes and type 1 diabetes complications.

Find out more about these research programs.

The ban was originally established by the NHMRC in 2004 to allow for further research into the possible side effects of the technique, particularly concerning the potential transmission of disease from animals to humans.

The NHMRC has now concluded that xenotransplantation research can proceed and that the associated risks with xenotransplantation are minimal and acceptable given the potential benefits.

Whilst the ban has been officially lifted, there are still a number of strict guidelines that need to be followed before xenotransplantation research can take place. These include the development and implementation of strict national frameworks, administered by the Therapeutic Goods Association, to ensure all clinical trials are sufficiently monitored and regulated. Animal welfare and ethics organisations will also be responsible for maintaining a high level of animal care.

Xenotransplantation research holds considerable promise for people with type 1 diabetes, particularly in the area of islet transplantation. JDRF funds a number of research projects in Australia and overseas looking into the possibility of using transplanted pig islet cells to replace the human cells lost during the disease process.

So far, xenotransplantation has had positive results in studies overseas. Researchers at two JDRF islet transplant centers in the United States were able to safely and effectively reverse diabetes in a number of animal models including monkeys by transplanting islet cells from pigs.

Dr Dorota Pawlak

“JDRF fully supports the NHMRC’s decision to allow clinical xenotransplantation research in Australia,” says JDRF Research Manager, Dr Dorota Pawlak.

“When used under strict ethical and scientific guidelines, xenotransplantation techniques have the potential to save the lives of thousands of people every year.”

“This is especially true for people on organ donor waiting lists and those living type 1 diabetes. These people urgently need to replace the insulin-producing cells destroyed by the disease and there is a very real possibility that this can be done using xenotransplantation.”

If you would like more information about xenotransplantation, go to the NHMRC website or call JDRF on 1300 363 126.