NZORD continues its support for AgResearch's transgenic animals program

Our joint submission with LDNZ to ERMA – December 2009

Since its inaugural meeting in September 2000, NZORD has maintained a position of consistent support for research into novel ways to produce the complex therapeutic proteins needed to treat a range of rare diseases. AgResearch’s transgenic animals research program is one promising avenue for the production of these proteins, but has been the subject of much opposition from some in the community with philosophical objections to this work. An extension of AgResearch’s approval to conduct this research was requested from ERMA, the Environmental Risk Management Agency, and in December 2009 NZORD joined with Lysosomal Diseases New Zealand to submit to ERMA in support of an extension of AgResearch’s approval. Here are the key points extracted from our submission:

  1. This submission is made in my roles as Chairperson of LDNZ and Executive Director of  NZORD. Both organisations work within their own specific objectives to support improved information and clinical care, and support research into rare disorders to work towards prevention, treatments and cures.
  2. Knowledge of the genetic causes of many rare diseases, and the disease process that follows from the incorrect protein expression, clearly demonstrate the potential for effective treatment or cure of many rare disorders by reintroducing the enzyme or protein that is missing, or is produced by the body in reduced quantity or misfolded form.
  3. Production of the complex human protein in a form that will be safe and effective as a therapy, will often require that the protein is derived from a mammalian system, to ensure the correct post-translational modifications. This is in order to provide the required levels of glycosylation, phosphorylation and other characteristics that will enable recognition and uptake of the protein by the patient's cells, and minimise the chances of rejection by the patient's immune system, or by the quality control organelles in the cell.
  4. Other methods of production of such proteins, where this can be done, may fail to produce proteins of the required complexity, or alternatively, in order to achieve adequate characteristics, may involve complex laboratory and industrial scale production process that ferment genetically modified animal cell lines. Such processes are expensive, environmentally stressful, and do not always produce the ideal functioning protein. The Royal Commission on Genetic modification accepted the evidence of Lysosomal Diseases New Zealand that transgenic animals are more likely to produce medically useful proteins. (RCGM report Chapter 7, para 103, page 161). This indicates limits to alternative methods of production that ERMA has to take into account. We urge ERMA to carefully note the evidence on these matters and to reject any contrary claims of opponents.
  5. In support of the need for this research to proceed with some urgency, we cite the recent experience of Genzyme, the world’s largest supplier of recombinant human therapeutics, which found itself in a production crisis during 2009. Its CHO cell fermentation plant had to be shut down and thoroughly sanitised  because of viral contamination in a bioreactor used for the production process for Cerezyme® (imiglucerase for injection) and Fabrazyme® (agalsidase beta). Urgent arrangement had to be made to plan the distribution of remaining stocks among patients world-wide and to determine how reduced access to these important therapies would be prioritised. There are indications that this crisis impacted on the development and availability of other life-saving recombinant therapeutic proteins such as Myozyme for Pompe disease, and Aldurazyme for Hurler disease, being undertaken by Genzyme. Later particle contamination caused further problems for all of the therapeutics, demonstrating clearly that current production methods are difficult to manage, very expensive, and vulnerable. As there is rapid development of more recombinant therapeutic proteins, the need for safe and reliable alternative production methods takes on increasing urgency, and transgenics is one means of production of these proteins that offers much promise.
  6. Evidence shows that human proteins produced by transgenic animals can be effective in treating the disease process in one rare disorder, Pompe disease. AgResearch also point to another recombinant protein licensed for medicine use in the European Union and in the US. This evidence demonstrates that the proposal to produce a variety of functional therapeutic proteins from transgenic animals, offers great potential for advancement in the control and treatment of rare diseases in humans. The fact that transgenic production has not proceeded for Pompe disease, instead a CHO cell fermentation process is used, confirms that more research is needed on transgenic production before its potential can be fully realised. AgResearch also point out that monoclonal antibodies may also be produced from transgenic animals and this indicates the urgent need for the necessary research to be carried out to establish sustainable and safe transgenic production.
  7. However there is a need to produce the protein in sufficient quantities to ensure supply, as well as with the required characteristics. A transgenic cow would be an ideal animal model to use to produce quantities of milk to ensure good supply of protein within the milk for extraction and medicinal use.
  8. We ask ERMA to note the consistency of this submission with that made to you on previous applications, and the stance adopted by both our organisations before the Royal Commission, in submissions to the Bioethics Council, and in commentary material published on our website news and issues pages and archive on this and similar leading-edge topics over recent years. See for example and
  9. For these reasons we offer our strong support for the AgResearch application.