Norwood Immunology, US hospital team up for tolerance trial

Melbourne immune therapy developer Norwood Immunology (AIM:NIM) has signed a collaboration agreement with the Massachusetts General Hospital in Boston to conduct a proof-of-concept preclinical trial to determine whether tolerance to donated organ transplants can be established without the need for prolonged immunosuppressants.

The trial, using kidney transplants in pig models, will be lead by clinical immunologist Dr David Sachs, director of the Transplantation Biology Research Centre at the Massachusetts General Hospital, and will be funded by Norwood Immunology with support from its US licence partner, TAP Pharmaceutical Products.

The first aim of the study will be to determine whether thymus atrophy can be reversed in aged pigs using TAP's drug Lupron.

The thymus gland is where T-cells are 'taught' to recognise and destroy foreign cells, such as those in a donor transplant, and also not to reject the body's own cells, or 'self'. The thymus degenerates with age, particularly post puberty, leading to a progressive decline in the output of T cells.

In the 1990s, Monash University researcher Prof Richard Boyd found that Lupron, by suppressing the production of sex-hormones that cause the thymus to atrophy, caused the organ to regrow and resume production of new T-cells.

Sachs has observed that tolerance to a donated organ can be achieved in young animals, which have an active thymus, but this cannot be replicated in older animals.

"We're speculating that that's because the aged animals no longer have optimum thymus function," said Suzanne Lipe, Norwood Immunology's chief operating officer.

The company hopes to have the results from the first aim of the study -- whether Lupron causes the thymus to regrow and increase thymic output of T cells -- within six months.

"There's no point paying a considerable amount of money to actually do the kidney transplant when you don't even know whether Lupron can reverse the atrophy," said Lipe.

If these results are positive, the second aim of the study is to determine whether older pigs that receive a kidney transplant, treated with Lupron and a 12-day course of immunosuppressants, can achieve the same graft acceptance as the younger animals observed by Dr Sachs, said Lipe.

The ultimate aim of the study is to determine whether a pig that receives a kidney transplant and a blend of donor and host haemopoietic stem cells (the stem cells that form blood and immune cells) in combination with Lupron, can create a new immune system and remove the need for immunosuppressant drugs altogether.

"If we got good proof of concept data that this platform facilitates organ acceptance then we might even think about partnering that aspect of this research with a large company that might have a core expertise in transplantation," said Lipe.

The company expects final results from the trial by the end of next year.