Islets transplantation: New Zealand experience

Xenotransplantation might alleviate the problem of donor organ shortage for the treatment of life threatening conditions. In 2009 the New Zealand Government approved a phase I/IIa clinical trial using porcine islet cells. That was the conclusion of 14 years of regulatory work on xenotransplantation in New Zealand. In 1995 Diatranz received an approval for a pilot study on islet xenotransplantation. Four subjects with and two without microencapsulation of neonatal porcine islets were transplanted. In 1997 the pilot study was voluntary stopped by the company due to the theoretical threat of PERV transmission to a human recipient. The company initiated a project on Xenovirology including intensive PERV study. The company also initiated a dialogue with the Ministry of Health regarding future clinical trials using porcine islets. The recommendation from New Zealand Regulatory Authority, Medsafe, was to follow the FDA guidelines on xenotransplantation. The Ministry also pointed out the need to have a nationwide consultation on xenotransplantation. In 2005 the Bioethics Council of New Zealand held a nationwide consultation where cultural, ethical and spiritual aspects of animal‐to‐human transplantation were discussed. The recommendation from the Council included that xenotransplantation should be allowed to be developed in the country, and that the government should develop a regulatory and decision‐making framework, set a monitoring body and a national register for xenotransplant recipients.The Ministry of Health also pointed out that there should be certain prerequisites for any xenotrial application, namely a donor herd free from all detectable viruses and harmful bacteria, that the Sponsor should have a GMP facility for product manufacturing, and an IANZ accredited diagnostic laboratory with the exhaustive virology program for patients’ follow‐up. LCT received a GMP license in 2001 and IANZ accreditation in 2007. An elaborate program on Xenovirology has been under development and implementation since 1997 (1–6). This program allowed LCT to allocate one specific herd of pigs that was free from all conventional pathogens and was also qualified as “null” pigs or pigs that do not have a transmittable PERV. These pigs are the animal‐founders for a DPF donor herd. Compliance with the requirements from NZ government allowed LCT to successfully complete its application for a clinical trial using porcine islets. In October 2009 the first New Zealand patient was transplanted with DIABECELL ® . The primary objectives for the phase I/IIa clinical trial is safety and improvement in blood glucose level reflected in a decrease of HbA1c (%) level. The secondary objectives include glucose lability, reduction of insulin dose and decrease in hypoglycaemia frequency. To date LCT reports that the trial is meeting objectives for safety. A reduction in the number of unaware hypoglycaemic episodes is also reported in transplanted patients. Prolonged insulin dose reduction for up to 30% is also reported. Safety data shows the absence of evidence of pig viruses’ transmission to the recipients. Data relating to all other endpoints will be reported once the trial has completed and is unblinded. References 1. E lliot RB , E scobar L , G arkavenko O, et al. No evidence of infection with porcine retrovirus in recipients of encapsulated porcine islet‐cell xenograft. Cell Transplant 2000; 9: 895. 2. G arkavenko O , O briadina A , M eng J , et al. Detection and characterisation of swine hepatitis E virus in New Zealand. J Med Virology 2001; 65: 525. 3. G arkavenko O , M uzina M , M uzina Z , P owels K , E lliott RB , C roxson MC. Monitoring for potentially xenozoonotic viruses in New Zealand pigs. J Med Virol 2004 Feb; 72(2): 338–44. 4. G arkavenko O , C roxson MC , I rgang M , et al. Monitoring for presence of potentially xenotic viruses in recipients of pig islet xenotransplantation. J Clin Microbiology 2004; 42: 5353–5356. 5. G arkavenko O , W ynyard S , N athu D , et al Porcine endogenous retrovirus transmission characteristics from a designated pathogen‐free herd. Transplantation Proceedings, 2008; 40: 590–593. 6. G arkavenko O , W ynyard S , N athu D , et al Porcine endogenous retrovirus (PERV) and its transmission characteristics: a study of the New Zealand designated pathogen‐free herd. Cell Transplantation 2008; 17: 1381–1388.