Transgenic plants offer hope for type 1 diabetes.

As reported in Autoimmune Market Outlook to 2012 autoimmune related disorders continue to maintain prominence within the global disease burden, having achieved a worldwide market growth of 9.4% over the 2002-06 period.

The autoimmune arena represents a key opportunity for drug development companies, with the potential for success largely attributable to substantial unmet demand, a significant patient population and the medical proclivity for long term treatments.

Type 1 diabetes is one high priority autoimmune disease as well as one of the most common chronic diseases in children and adolescents; about 151,000 American below the age of 20 years have diabetes and while a growing number of these individuals have type 2 diabetes the majority have type 1 disease. Diabetes often leads to long term complications, a problem that increases with duration of disease and so type 1 diabetes remains a particular concern. While good glucose control through injectable insulin is able to reduce the onset of complications in later life new strategies that can reverse the disease represent the holy grail of diabetology.

Interleukin-13 (IL-13) is a pleiotropic regulatory cytokine with the potential for treating several human diseases, including type 1 diabetes. However thus far, conventional expression systems for recombinant IL-13 production have proven difficult and are limited by efficiency. In an article from Plant Biotechnology Journal, soon to be highlighted on DailyUpdates, Wang et al report on the use of transgenic plants as a means of producing human IL-13 (hIL-13).

Transgenic plants represent an exciting opportunity in the emerging arena of biologics (see Transgenic Animals and Plants in Pharmaceutical Research and Manufacturing). With the mapping of the human genome and the concomitant explosion of proteomics, a steady stream of biopharmaceuticals have been launched. As the rate of regulatory approval for biopharmaceuticals increases, the number of products reaching the market will impose unprecedented demands on the industry’s biomanufacturing capacity. Whether or not this will create a biomanufacturing bottleneck is a hotly debated issue in the industry. One issue that is not debatable, though, is the high cost of manufacturing biopharmaceuticals. While biopharmaceuticals produced in bacterial or mammalian cell culture bioreactor facilities have proven to be very effective therapeutic agents, they are also among the most expensive drugs produced, and there is doubt that the current pricing models are sustainable regardless of these agents’ efficacy.

One way to address these concerns is through the use of transgenic plants to manufacture biopharmaceuticals.

Wang and colleagues have taken this approach producing DNA constructs containing hIL-13 cDNA that were introduced into tobacco plants. hIL-13 protein efficiently accumulated in transgenic plants with an expression level as high as 0.15% of total soluble protein in leaves. Multiple forms of plant-derived recombinant hIL-13 resulted from differential N-linked glycosylation. Of significant interest, plant rhIL-13 was highly resistant to proteolysis. In particular, resistance to gastric and intestinal fluid digestion was suggested.

These exciting findings suggest that not only can plants be harnessed to produce IL-13 at high levels reducing production costs, but also that the protein produced may be active orally removing the need for injection, a route of administration expected for such a molecule

Further development of this research is eagerly awaited as are studies establishing IL-13 as a therapeutic option for the treatment of type 1 diabetes