A new mouse model in the quest for new drugs

At the Research Center Borstel, a mouse model has been developed in which tuberculosis infections can be simulated better than before. In these models, the development of cell lesions—so called granulomas—which are similar to those found in the human lungs can be induced, amongst other things. In combination with an imaging method, new substances can be efficiently tested for their efficacy against tuberculosis bacteria. With this preclinical approach, the scientists intend to accelerate the discovery of new drugs and improve dose finding. 3000 natural active agents with an in vitro anti-tuberculosis effect are available for further investigations. Through collaborations with the European-African consortium PanACEA, many promising drugs can subsequently be brought into clinical trials more rapidly and benefit patients worldwide.


Validation and application
The newly developed mouse model will initially be validated by comparing results from standard treatments to clinical data from humans. The model is expected to be more reliable than conventional mouse models. Risky or not very promising agent candidates can be identified early and consequently the costly clinical development can be stopped in time. Furthermore, the scientists want to use the model to find agents that do not cause resistance. Additionally, when combined with mass spectrometry imaging methods, the model can be used to determine the optimal dose for a specific treatment form. Moreover, with these imaging methods, the scientists want to observe the vitality of bacterial cells in-vivo using a specially developed assay.
Contact: Christoph Hölscher, Research Center Borstel; Michael Hölscher, University of Munich; Norbert Heinrich, University of Munich

From mice to humans
After validation, the new mouse model could replace imponderable preclinical models. Newly discovered agents, as well as existing new agents (BTZ043, Q203, GSK´147, bedaquiline and delamanid), will be tested both individually and in combination, and subsequently go into clinical testing on humans.
: Michael Hölscher, University of Munich; Norbert Heinrich, University of Munich; Christoph Hölscher, Research Center Borstel