Sunday | 7 September, 2008
Australian Biotechnology News
Pig islets ready to Rocky and roll
LCT is set to start a pig islet transplantation trial for type 1 diabetes that may have a profound effect on the debate over Australia’s xenotransplantation moratorium in 2009.
Kate McDonald 11/12/2007 11:18:26

Rocky
Rocky
Additional Resources

Newsletter Subscription

Sign up for our Australian Life Scientist newsletters!
The latest, most important headlines from Australia and around the world.
A daily e-mail from Australian Biotechnology News, with the latest, most important headlines from Australia and around the world.

Rocky the pig may not be too aware of what's going on, but his keepers at Living Cell Technologies' (LCT) breeding facilities in New Zealand are eagerly awaiting the signature of one very important man.

That man is the country's health minister, Pete Hodgson, who is expected to give the go-ahead for an encapsulated porcine islet cell transplantation trial at Auckland's Middlemore Hospital.

LCT has received all of the regulatory and ethical approvals required and the trial just awaits Hodgson's signature. It will be the second such trial for LCT, which is conducting another at Moscow's Sklifosovsky Institute, and it will be small, involving eight patients.

However, the trial's effect on the looming debate about the xenotransplantation moratorium in Australia, due to be re-considered in 2009, might be another matter.

Professor Bob Elliott, LCT's co-founder and medical director, puts his views on the potential of ending the moratorium in 2009 bluntly.

"It will end a great deal quicker than that if we get people off insulin long term," he says. "If it is working, then clearly the benefits would outweigh any possible, highly unlikely, risks."

And it does seem to be working. LCT's case on the public relations front has been boosted recently by two notable examples: one is Michael Helyer, the Auckland man who took part in an early trial and was happy to make international headlines when it was found that he still has functioning porcine islet cells making small amounts of insulin 10 years after the transplant.

The other was the release of very early results in the Moscow trial, in which one patient has come off insulin injections altogether.

Although it was an unusual step, LCT was obliged to release early results about the Russian patients because it is listed on the Australian stock exchange, which requires companies to release information that could affect the share price.

And the whispers from the Moscow trial were becoming a roar by September: the first patient, a 26-year-old man, has had his insulin requirements reduced by almost 40 per cent after the first of two transplants. The second, a 40-year-old woman, no longer required insulin after a month.

"We knew it was starting to leak out from Russia because we were getting people we didn't know popping up who had heard about the results," Elliott says.

"We'd made that decision [to announce early results] ahead of the second patient coming off insulin, and that's the Holy Grail of course. That news was getting around too. There is no obligation on the Russians to retain secrecy - there were hundreds of people in Moscow who knew what was going on."

Elliott is extremely confidant about the efficacy of his technology but knows there will still be many doubters who will require a lot of delicate persuasion.

There are those who point to the zoonotic disease risk, in particular the risk of transmission to humans of porcine endogenous retroviruses (PERV), the driving force behind the halting of trials in 1997 and the subsequent worldwide moratorium.

This is where Rocky and his colleagues come in. Rocky is a very special pig indeed, bred from an isolated and disease-free herd resident on Auckland Island, south of New Zealand.

"The animals we use do not produce PERVs," Elliott says. "They've got the sequence in their genomes but they do not produce infective particles and they cannot produce them because they don't have the right genetic code. It's defective, so they've been designated null pigs.

"That's the basis we work on but some people worry they might mutate again, so we are following all of the guidelines the FDA has laid out. Thousands of exposures to full-length, infective PERVs have been carried out by mistake, when people were given factor VIII from pigs, repeatedly given it intravenously, but nobody came to any harm by actually receiving the virus. It was a genuine scare and we stopped just like everyone else but it has turned out to be a red herring."

Then there are those who argue that microencapsulation of islet cells has been tried for 25 years and doesn't work, or just doesn't work well enough, allowing the problem of immune rejection to rear its ugly head.

A big issue for any xenotransplantation is the alpha 1-3 galactose epitope, or alpha-GAL, which all animals bar humans and Old world monkeys such as baboons and macaques carry on their cells.

"Man is very peculiar in this respect and it does mean that man has acquired antibodies against all animal cells," Elliott says.

"This is a particular problem but it is antibody-dependent, complement-mediated, so by doing the encapsulation that is not a problem. It eliminates the immediate rejection that is seen with pig cells put into humans."

Elliott says it is also essential to perfect the technology so that macrophages aren't attracted to the islets, which means weeding out all the dead ones.

"If you put dead cells in then the macrophages will come. So we had to make sure that we had completely viable cells. Again it was a matter of technology and treating the cells as gently as we could.

"The other thing was to make sure that as far as possible our encapsulation was complete and that we didn't have some unprotected cells - they would have attracted macrophages and they'd start excreting cytotoxic cytokines and could kill off even the innocent bystanders. We had to make sure there were no duds in there.

"A lot of people say this can't work. Well, it does work, but not because of any great leap of science. It has been a slow grind with a very old idea. It was just a matter of perfecting it so that it did what it was supposed to do."

Australian Life Scientist Member Login

 
Sponsored Links