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MHH project LuFex aims to develop a new inhalative treatment with a plant-based anti-fibrosis drug and is receiving 800,000 euros from the biomedical start-up incubator IBT Lower Saxony.
Tissue damage can affect many organs and is responsible for about half of all deaths in industrialised nations. This includes the development of fibrosis, in which the original tissue is replaced by connective tissue cells (fibroblasts). The activation of fibroblasts is an important key event and leads, among other things, to organ stiffness, insufficient oxygen supply and ultimately to organ dysfunction. One example of this is idiopathic pulmonary fibrosis (IPF), a chronic disease in which lung tissue becomes scarred and leads to severe breathing difficulties. Although there are already two drugs on the market to treat pulmonary fibrosis, they only provide limited relief and also have many side effects.
Professor Dr Dr Thomas Thum, Director of the Institute for Molecular and Translational Therapy Strategies at the Hannover Medical School (MHH), is now seeking new and effective compounds that prevent fibrosis and protect the lungs. In his LuFex project, he wants to develop a new drug against pulmonary fibrosis that can be easily inhaled. The Institute for Biomedical Translation (IBT) Lower Saxony is supporting the research project with 800,000 euros over two years. The aim of the biomedical start-up forge is to accelerate the transfer of cutting-edge research in the life sciences in Lower Saxony and to bring entrepreneurial ideas to the world.
Strong antifibrotic effect
IPF is a progressive disease and is ultimately fatal. After diagnosis, patients live on average only three to five years, which is shorter than for many types of cancer. Patients suffer from increasing shortness of breath, chronic coughing, fatigue and weight loss. As the disease progresses, many require supplemental oxygen or even a lung transplant. In their search for a suitable agent to combat pulmonary fibrosis, Professor Thum and his team searched a so-called natural product library and analysed 150,000 substances using bioinformatics. Another 500 bioinformatically selected substances were then examined directly in the laboratory. ‘We found a natural plant substance and tested it directly on human heart, liver and lung fibroblasts,’ says the fibrosis specialist. The result: the substance strongly suppressed the fibrotic reaction. The researchers then tested the antifibrotic effect just as successfully in living organ sections. The material for the wafer-thin tissue slices comes from the MHH Clinic for Cardiac, Thoracic, Transplantation and Vascular Surgery and is, so to speak, tissue waste from diseased, fibrotic organs that were removed during a transplant. These organ slices live on in a nutrient solution for many days or even weeks.
Further variants found for lower dosages
In order to improve the effectiveness of the natural substance while at the same time reducing harmful side effects, the team has constructed more than 30 variants of the best lead compounds. ‘We have already tested several of them in cell cultures and in tissue sections of heart, lung and liver,’ says Professor Thum. ‘And we have already identified some variants that show further improved antifibrotic activity at significantly lower doses.’ Next, he wants to test the drug in a few more models. ’This is important to find out the optimal formulation, i.e. which excipients we need to add to develop an effective drug.’ After the initial funding of his project by the IBT, Professor Thum and his team are seeking further funding – for example for later clinical studies, which are a prerequisite for bringing a drug to market. The scientist is convinced that they will succeed. ‘Our work will lead to the development of a novel treatment approach for organ fibrosis, a disease that affects millions of people worldwide and for which there are currently insufficient treatment options.’
For further information, please contact Professor Dr. Dr. Thomas Thum, thum.thomas@mh-hannover.de, phone +49 (0)511 532-5272.
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