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HOT Screen GmbH - models for studying diseases

HOT Screen GmbH from Reutlingen, Germany, develops human organotypical (HOT) cell culture models related to the human immune system for the assessment of drug activity profiles and the selection of suitable drug candidates. For the past 17 years or so, Dr. Manfred Schmolz, managing director of HOT Screen GmbH, and his scientific team have devoted their creativity and energy to the development of such physiological models. The sophisticated models are made with differentiated cells and can be adapted to a broad range of different diseases - including rheumatoid arthritis, osteoarthritis, Crohn’s disease, neurodermatitis, COPD, asthma and many others. Pharmaceutical companies and the biotechnology industry contact HOT Screen GmbH with specific issues and Dr. Schmolz not only listens carefully to their requirements, but in many cases has a suitable model already available.

Around 90 percent of all drug candidates fail to complete the clinical development and marketing approval process. The decision to abandon the drug candidate usually occurs relatively late in the drug discovery process after many years of preclinical and clinical research. Dr. Schmolz is convinced that it is possible to improve the effectiveness of the processes. It is also possible to decide at an earlier stage whether it is worthwhile investing in the further development of a substance class under investigation. However, this decision depends on the availability of differentiated, organotypical models that can be used for the preclinical evaluation of drug candidates.

HOT cell culture models - design and function

Schematic of HOT Screen GmbH ’s co-culture models – here, an intestinal epithelium/whole-blood co-culture. © HOT Screen GmbH
HOT Screen GmbH’s human organotypical (HOT) test model consists of two compartments (chambers). The upper chamber contains tissue cells such as differentiated bronchial epithelial or epidermal cells; the lower chamber contains a customised whole-blood culture which represents the immune system in its full complexity and is optimised for each individual tissue type. The two chambers are separated from one another by a porous membrane, enabling the in vivo-like cross-talk between the cells of the two compartments. HOT Screen GmbH’s multi-analytical profiling system that can analyse several dozen biologically relevant molecules simultaneously, enables the characterisation of drugs as well as the discovery of new drug candidates. The cell culture model can be used to assess the activity range of test substances as well as that of complex preparations.

HOT cell culture models - from physiological knowledge to appropriate drugs

Complexity of the human immune system. © HOT Screen GmbH

Since it is not possible to implement all the functions of an organ such as the kidneys, the HOT Screen GmbH models can represent neither a complete nor a real in-vivo situation. That said, this is not HOT Screen GmbH’s primary objective. Schmolz knows from his own experience that a physiological section is perfectly sufficient for finding answers to relevant questions. Of course, Schmolz has specific ideas as to how certain models could be optimised in physiological terms.

Due to their interaction with the immune system, Schmolz believes that the inclusion of neuroendocrine system cells or the liver in the model would be advantageous in the evaluation of drug activity profiles. However, even though the model can be developed further, this is not what the pharmaceutical industry is primarily seeking. Any characterisation of active drug ingredients must lead to highly reproducible results, but it goes without saying that this becomes increasingly difficult with the increasing complexity of a drug. Testing drugs in animals is not a satisfactory solution either, as the results cannot be transferred 100% to the situation in humans. 

Disease-specific models

Immunomodulatory effects of bacterial products in co-cultures consisting of intestinal epithelial cells and whole blood. © HOT Screen GmbH
The company has four co-culture systems, targeting conditions of the skin, gut, joints and lungs. They have become standard applications in the pharmaceutical industry and in the biotech sector. The company’s skin model determines drug activity profiles by measuring the resorption of active drug ingredients by deeper skin layers. Information about inflammatory responses provides information about a drug’s pathophysiological effects and its activity profile. The gut model generates information on the absorption of immunologically active substances and their effect on the human immune system. As the model also provides information about the drug’s potential effects on the intestinal epithelium, it is also suitable for investigating chronic gut diseases such as Crohn’s disease. The lung model investigates the activity profile of inhaled drugs, for example those used for the treatment of asthma. The model can also be used to investigate drugs that are administered systemically. This is done by adding the substances to the whole-blood chamber. This model is also suitable for investigating severe long-term diseases such as COPD (chronic obstructive pulmonary disease). HOT Screen GmbH already has new plans. On the one hand, it plans to optimise the models further by including specific cell types to make the investigations even more in-vivo like. On the other hand, HOT Screen GmbH also wants to create something new: “We are working on a diabetes model and also have plans to tailor our co-culture models to other diseases,” said Schmolz.

EDI GmbH was renamed on the 1th July 2014 as HOT Screen GmbH.

Further information:
Dr. Manfred Schmolz
HOT Screen GmbH
Aspenhaustr. 25
72770 Reutlingen
Tel.: +49 (0)7121/434103
E-mail: m.schmolz(at)hot-screen.de

Website address: https://www.gesundheitsindustrie-bw.de/en/article/news/hot-screen-gmbh-models-for-studying-diseases