Researchers welcome xenotransplantation guidelines

Australian researchers have welcomed the National Health and Medical Research Council's draft guidelines on xenotransplantation, released yesterday.

BresaGen vice-president and chief operating officer Dr Meera Verma said the draft guidelines opened the way for a more proactive approach to the research.

"It is important to look at emerging technologies proactively rather than after they have hit," Verma said.

"[The guidelines] are looking at what the issues would be and also address the fact that safety studies have to be conducted along the way, so that the path to clinical trials should be fairly straightforward."

She said it was helpful to know how the regulators were thinking because it made it easier to work together to move projects forward.

One of BresaGen's research projects involves the development of a GAL knockout pig with altered complement factors to reduce the chances of rejection, with a large component of the work backed by the Juvenile Diabetes Research Foundation.

Chris Juttner, the company's vice-president of clinical development, said the guidelines would facilitate discussion and help to educate the public, as well as pave the way for a well-regulated environment.

"The regulatory model they propose is very satisfactory," he said. "It has appropriate representation of all expert and stakeholder groups. Experiments done by cowboys without proper regulatory oversight bring xenotransplantation into disrepute."

President of the International Xenotransplantation Association, Prof Ian McKenzie, described the draft as "responsible guidelines that indicate how xenotransplantation could be done".

But he said that just because they were written up did not mean that such operations would begin immediately.

"I think it is crucial because there are groups in Australia thinking about xenotransplantation in the future, and it's better that they can factor in these guidelines now," McKenzie said.

McKenzie said that while some people might view the use of animal organs in humans as abhorrent, the shortage of donor cadaver organs meant the technology could prove the difference between life and death.

The xenotrans community

According to Prof Tony d'Apice of St Vincent's Hospital in Melbourne, there are four main research groups working on xenotransplantation in Australia.

As well as his group at the Immunology Research Centre at St Vincent's, d'Apice said that the other major players in Australia included:

• Prof Phil O'Connell at Westmead Hospital in Sydney,
• Prof Bernie Tuch at the Prince of Wales Hospital in Sydney, and
• Prof Ian McKenzie and Prof Mauro Sandrin at the Austin Research Institute in Melbourne.

d'Apice has been working with BresaGen to develop genetically modified pigs for transplantation purposes.

"We're trying to develop GM pigs so their organs can be transplanted into humans," he said.

He said that while hearts and kidneys were long-term xenotransplant goals, transplanting of porcine pancreatic islet cells to treat diabetes was likely to happen first, and was the focus of most of the research in Australia at present.

Prof Bernie Tuch's Diabetes Transplant Unit at the Prince of Wales Hospital in Sydney is examining the use of foetal pig pancreatic cells for transplants.

A year ago, Tuch's lab applied to the NHMRC for permission to do a xenotransplant into a patient, but was knocked back. Since then, the group has been gathering further information to support future applications.

"We're very positive about the guidelines and it's something we have been pushing for a long time," Tuch said.

He said that his team had demonstrated the ability of pig cells to reverse diabetes in mice and in pigs. It is currently putting pig cells into monkeys to provide the final information required before human clinical trials can be considered.

The team has also developed a strategy to ensure safety of the pancreatic transplant and have come up with methods to monitor the transplant in the first few weeks.

"We are trying to optimise the conditions for human transplants," Tuch said.

He stressed that at this point xenotransplants of pig pancreatic cells into humans would not be of benefit for most diabetics and that the need to use anti-rejection drugs would also make it unsuitable for many people.

At the Austin Research Institute, Prof Ian McKenzie and Prof Mauro Sandrin are interested in reducing the immune response to xenotransplants, and are using transgenic approaches to overcome transplant rejection.

Their particular transplant targets are pancreatic islets, kidneys and the heart, according to Sandrin, and like the other groups, they are using pigs as the source of the transplant.

"I think it is good that these guidelines have come out now," he said. "We need public consultation before going into clinical trials."

McKenzie and Sandrin have also recently set up a company for xenotransplantation R&D, called XenoTrans.