Tobacco use triggers a number of common diseases in humans including heart disease and lung cancer. However, a group of scientists from Europe may be tobacco's saving grace. They successfully used genetically modified tobacco plants to generate medicines for a number of autoimmune and inflammatory diseases. The study was part of the Pharma-Planta project, which was funded under the EU's Sixth Framework Programme (FP6) to the tune of EUR 12 million. The study's results were recently published in the open access journal BMC Biotechnology.
The scientists targeted the creation of transgenic tobacco plants with the capacity to generate biologically-active interleukin-10 (IL-10), a small protein known as a cytokine that regulates the immune system.
Led by Professor Mario Pezzotti from the University of Verona in Italy, the team tested two different versions of IL-10 (viral and murine) and produced plants in which this protein was targeted to three different compartments within the cell in order to assess the most effective one.
The researchers noted that oral administration of this cytokine alone, or in combination with disease-associated autoantigens, could offer protection from the onset of a specific autoimmune disease through the 'induction of oral tolerance'.
Furthermore, the team found that the tobacco plants successfully processed both forms of IL-10. Active cytokine was produced at high enough levels making it possible to use tobacco leaves without wasting a lot of time for extraction or purification. Transgenic plants are able to increase proportionally at low cost and with low maintenance.
'The fact that they can be eaten, which delivers the drug where it is needed, thus avoiding lengthy purification procedures, is another plus compared with traditional drug synthesis,' explained Professor Pezzotti. 'These results clearly demonstrate that tobacco plants can express the viral and murine IL-10 genes, process and assemble the corresponding proteins into functional, biologically-active dimers,' he added.
The scientists are eager to use the plants to determine whether repeated small doses could help prevent type 1 diabetes mellitus (T1DM), in combination with other auto-antigens associated with the disease. They have set their sights on the 65-kDa isoform of the enzyme glutamic acid decarboxylase (GAD65) for the testing.
'The accumulation levels of both viral and murine IL-10 in tobacco leaves are high enough to provide sufficient material for oral administration in oral tolerance studies using the available mouse models,' Professor Pezzotti said.
'This study paves the way to performing feeding studies in mouse models of autoimmune diseases, which will allow the evaluation of the immunomodulatory properties and effectiveness of the viral IL-10 in inducing oral tolerance compared to the murine protein.'
Collaborating with the University of Verona were the Institute for Molecular Biotechnology (Germany), Fraunhofer Institute for Molecular Biology and Applied Ecology (Germany), Max-Planck-Institute of Molecular Plant Physiology (Germany), the University of Natural Resources and Applied Life Sciences (Austria) and the University of Perugia (Italy).
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