Research of the group Theuring

The group is using methods and state-of-the-art techniques in biomedical research to identify new potential drug targets, to validate drug targets and already known key molecules for their involvement in pathophysiological processes, and, in the frame of a R&D program, to characterise and test new pharmacological active compounds for their abilities to act as therapeutic drugs in clinical dementia, ie Alzheimer’s Disease. These studies represented the final phase in preclinical drug testing and paved the way for the future drugs to enter into clinical trials.

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Therefore, transgenic techniques in mice are being employed to study gene regulation and function and to generate animal models relevant for human diseases. Such animal models have given essential insights into the regulation and function of genes in the context of the whole organism.

They further provide a basis for transcriptomics and/or proteomics as well as for the identification and characterization of genes and proteins involved in human disease processes. In the last CCR report we had reported on a major breakthrough in the treatment of Alzheimer’s disease (AD) in the line of our successful phase II clinical trial. The product – rember®, a novel form of methylthioninium chloride (MTC) – is the first drug to act on the tau tangles discovered by Alois Alzheimer.

The teams of the University of Aberdeen and the Charité, working with Tau Rx Therapeutics – a Singapore-based company spun out of these two Universities – developed a novel treatment based on an entirely new approach which targets the tangles, aggregates of abnormal fibres of Tau protein forming inside nerve cells in the brain. By employing our transgenic mice a group of second-generation rember® derivatives had now been discovered and successfully tested.

TauRx has now initiated preparations for Phase 3 studies in mild and moderate AD. A very similar approach is used to identify new drugs acting on Parkinson’as Disease (PD). Transgenic mice modelling PD have been generated and a detailed analysis of these model systems identified the relevant transgenic lines which will be used to test newly synthesized substances for their activity to fight PD. In parallel, we use different inbred strains of mice to analyse for gender and age related effects in cardiovascular function. By employing modern 2-dimensional gel electrophoresis, mass spectrometry, and phosphoproteomics we hope to identify key proteins being responsible for and mediating these changes.

These candidates could then provide an entry point into defining a more specific pharmacotherapy for these alterations. In addition to their importance as model systems for human disorders, transgenic animals furthermore represent valuable tools for the characterization of general cell biological processes, providing the possibility to analyze the role of distinct molecules in an in vivo context. Insights gained in these model systems will improve our understanding of fundamental molecular mechanisms governing e.g. the regulation of tight junction permeability, thereby facilitating the identification of new pharmacological approaches for the modulation of these processes.

Transgenic animals expressing various components of the RhoA signalling pathway as well as in vitro systems mimicking the intestinal barrier furthermore provide an insight into the effects of established and innovative pharmacological compounds on tight junction permeability and intestinal barrier function.