Pulmonary medicine from a moss bioreactor
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- The natural habitat of the moss Physcomitrella patens is in North America and Eurasia. Source: Pirex/Wikimedia
01.02.2012 -
Breathing without getting air is a simple way of describing the disease known as Idiopathic Pulmonary Fibrosis (IPF). This condition causes the alveoli to shrink and to be able to absorb only very little oxygen, says Andreas Günther, a professor at Gießen University Hospital, explaining the mechanism behind IPF. Only half of patients can expect to survive the first three years. Together with his own research team and the Freiburg-based company greenovation, the specialist in lung diseases hopes to develop different approach to current therapies. His project is planned to take three years and is being funded with €833,000 as a part of the Health Research program from the German Federal Ministry of Research. On 30 January, Parliamentary State Secretary Helge Braun announced the funding decision at the University of Gießen.
Nearly every day, Andreas Günther and his team are occupied with the two diseases IPF and acute respiratory distress syndrome (also known as 'adult respiratory distress syndrome' (ARDS)) and their serious symptoms. IPF is common among the elderly, and ARDS can also occur following the inhalation of smoke, after accidents, or after the inhalation of vomit. In both cases, the pulmonary alveoli, which are responsible for the gas exchange of carbon dioxide and oxygen, become limited in their function. The otherwise the fine structure is penetrated by thick connective tissue, and is unable to sufficiently develop, meaning that patients must exert themselves in order to breathe.
A complex protein complex
The scientists are now receiving help from a special sort of moss. As some in the field might assume, the moss does not serve as a source of essential oils to facilitate breathing, but as a mini factory for an active ingredient. The moss Physcomitrella patens has been a firm fixture on the scientific scene for some years, and in this case there is no doubt about it is intended to produce. Back in 2007, Günther developed a protein complex with the somewhat burdensome name surfactant protein B-urokinase (SPUC). The enzyme urokinase is able to dissolve the fibrin clotting in the lungs. "The problem is that the clot is found in a slimy film that is produced by the lungs to protect the vesicles. Urokinase is soluble in water, and so it is unable to penetrate the greasy film," says Andreas Schaaf, Scientific Director at the Freiburg company greenovation, the business partners in the project.
In the new approach, the enzyme is bound to the lipid-soluble protein surfactant B in order to overcome the mucus barrier – an idea that has now been proven to work by the researchers at the University of Gießen. The protein complex does indeed exhibit a protective and therapeutic effect on the lung cells. Transgenic mice in whose lungs the protein was produced were considerably less likely to suffer from lung infections, and the death rate decreased in diseased animals.
However, actual pharmaceutical production is now faced with a number of challenges. "SPUC is difficult to produce because of its fat-soluble properties," says Schaaf. "For this reason we see problems with the cell membrane in animal cell cultures." And so the research team at the University of Gießen turned to greenovation, where the team headed by plant biotechnologist Ralf Reski had already recognised that the moss Physcomitrella patens could be easily cultivated and genetically modified, making it a possible mini-factory for pharmaceuticals.
In 1999, to turn this principle into practice, the company greenovation was founded. Four years ago, the full genome of the Physcomitrella patens moss was decrypted by scientists working at the University of Freiburg, and the first attempts to create antibodies with the moss are now underway at Merck Serono.
SPUC in "medium scale"
And now SPUC is also set to be produced using the moss Physcomitrella patens, initially in small laboratory quantities that will be used to analyse the protein complex before commencement of clinical testing. "We are creating stable transgenic moss lines that are equipped with the gene construct for SPUC," says Schaaf. The first objective is for the protein to enter production in 500 litres of culture – a medium scale, says the working group leader. The theoretical design for the gene construct in the moss is already completed; cloning of the gene sequences will begin in the laboratory in the next four weeks. The researchers expect to be finished in 18 months.
Alongside SPUC, greenovation is hoping to produce five other drugs using their moss. This year will show whether the technology is proven, says Schaaf. "Already in 2012, we will make the decision of whether or not to go to the clinic."
Author: Cornelia Kästner
