Issues Magazine

Bioethics – This Little Pig Went to Market: Trialling Porcine Cell Transplants

Issues 86: Bioethics

Issues 86: Bioethics

By Bob Elliott

Live pig cell transplants for the treatment of human diseases seemed improbable and risky but the risks have not eventuated, and evidence of clinical benefit is accruing. Despite the Australian moratorium on xenotransplantation being recently lifted, it looks as if Australians who want to try such treatments will have to wait.

Three years ago I wrote for Issues about the unwillingness of the Australian Government to allow clinical trials of live pig cell transplants in an attempt to improve the treatment of severe type 1 diabetes.

Last year, the 2005 moratorium on xenotransplantation in Australia was lifted by the National Health and Medical Research Council, but there is little likelihood of such trials taking place in Australia in the near future. The only Australian company that currently has the facilities to carry out such trials is fully engaged in doing so in New Zealand, Argentina and Russia, with one other country in the offing.

The reason for the moratorium was mainly that there was a risk of unleashing a pig virus infection akin to HIV, not only on the recipient of a pig cell transplant but also on the community at large. Such fears have not been realised, although strict precautions about the donor herds still need to be taken to prevent pig-to-human infection transmission.

Diatranz Otsuka is a New Zealand-based joint venture company established in 2011 between the Japan-based Otsuka Pharmaceutical Factory and the Australian-based Living Cell Technologies (LCT). The joint venture company now owns a unique disease-free pig herd recovered from the remote sub-Antarctic Auckland Island. These pigs were set ashore in 1806 by the British captain Abraham Bristow. They were a mixture of small nondescript European domestic pigs and an English breed: Glouster Old Spot. In two centuries of isolation from other land-based mammals in this fierce climate, these pigs have lost all microorganisms capable of infecting people. This herd has been transferred to strict bio-isolation facilities in New Zealand and used as the source herd for the cells used in human transplants. The herd is regularly monitored to make sure its pristine state is preserved.

Fifty-five transplants of insulin-producing cells from these pigs into humans have now been carried out over the past four years, showing a lack of evidence of porcine virus infection. Treatment involves transplanting pig pancreatic islet cells into a patient’s abdomen to boost insulin production and help regulate blood glucose levels. The cells are encapsulated to prevent the immune system rejecting them as foreign. This technology ensures the cells can deliver their beneficial effects without the patient requiring immunosuppressant drugs. Most transplant recipients showed evidence of pig islet function. Xenophobia is no longer justified.

The series of clinical trials required by regulatory agencies before allowing widespread use as a treatment are lengthy and arduous. Results to date have demonstrated a beneficial effect (for example, a consistent reduction in severe hypoglycaemic events without an increase in HbA1c, a measure of long-term blood glucose levels) in type 1 insulin-treated diabetics who are having persistent trouble in balancing their dose of insulin with activity, food intake and other lifestyle variables.

Blood glucose levels that are both too high and too low are often encountered, and these swings can be life-threatening. Some patients require significant time and resources from specialist healthcare professionals and have a poor prognosis: lower quality of life, more microvascular and pregnancy complications and shortened life expectancy.

Various improvements in the pig product itself, and the way in which it is administered, are being tried out. The pig cells are coated with a semi-permeable membrane that neutralises the human body’s attempt to remove the foreign cells. No immune suppressants, which frequently produce severe side-effects, are used.

What, then, is the future of this procedure? The final round of clinical trials will start in early 2013 and be completed by the end of 2014. They will not include Australia. Permission to offer the treatment will be sought in those countries undertaking the trials.

Initially, Australians wanting this treatment will have to travel to New Zealand. There is little pressure to undertake xenotransplantation in Australia as the entry cost (including the cost of a pathogen-free herd and a certified manufacturing facility) is high (upwards of $25 million), and the regulatory pathway untried. Even a pilot pig facility and suitable manufacturing laboratory requires a very high capital investment.

Cell transplantation may offer an entirely new paradigm for the treatment of human disease. Mature cells may be harvested from humans (after death), but this source will always be limited. Training human stem or precursor cells to undertake special functions is being attempted without much in the way of clinical results yet. Cells may be genetically altered to undertake special functions, and this technology has been widely used in preclinical studies.

Without (and sometimes with) immune suppression, foreign islet cells are rejected. Current techniques to overcome this include the immune barrier strategy used by Diatranz Otsuka Limited, immune suppressant drugs or cells genetically altered to reduce the immune response.

Xenotransplantation of unaltered pig cells offers the advantages of self-regulatory function and probably a higher degree of safety than can be assured for stem cells or genetically altered cells.

Already a different pig cell transplant procedure is approaching clinical trials. LCT has developed preclinical technology to implant choroid plexus cells into the substantia nigra to treat Parkinson’s disease. These cells produce a cornucopia of brain protective and healing growth factors capable of regenerating brain cells lost to a variety of toxins. Both rat and monkey models of Parkinson’s disease have demonstrated functional and anatomical recovery after implantation of micro-encapsulated neonatal pig choroid plexus cells.

Other neurodegenerative brain diseases such as stroke, Alzheimer’s disease and Huntington’s disease may be similarly amenable to this form of regenerative treatment. And it doesn’t stop there.