Safety & Drug Testing

The cardiovascular system is regulated by a complex interplay of pressure dynamics, neurological signals, chemical compounds and other physiological factors. Consequently, treatments for conditions such as pain, diabetes mellitus or cancer can unintentionally lead to life-threatening cardiovascular complications.

To assess drug safety in the context of cardiovascular diseases, we utilize human primary cells, immortalized cell lines, iPSC-derived cells, complex organoids, patient samples – including blood and living human cardiac slices – and animal models. Our assays enable the development and validation of therapies in close alignment with human organ physiology enhancing the relevance of our findings and has the potential to significantly reduce the time from discovery to clinical application.

As part of this effort, we have developed and patented treatment strategies for conditions such as Doxorubicin-induced cardiotoxicity. Anthracyclines, including Doxorubicin, are widely used to treat various cancers and can lead to acute myocarditis in 1-2% of patients, with a mortality rate of approximately 30-50%. Cancer itself remains one of the most frequent causes of death worldwide. However, even after successful cancer treatment, survivors face an increased risk of developing cardiovascular disease – the other leading cause of mortality in the Western world. Recent studies show that patients treated with anthracyclines have more than twice the likelihood of developing heart failure within 20 years, highlighting the urgent need for cardioprotective strategies.

Our research addresses these dual challenges by focusing on novel therapeutic targets, including various RNAs and RNA-binding proteins, as well as pioneering heart-targeting strategies using AAVs and LNPs. The significance of our approach is underscored by publications in high-impact journals such as European Heart Journal, Circulation Research, and Molecular Therapy. Moreover, our work is supported by prestigious funding agencies, including the ERC Advanced Grant (Project: REVERSE).

Key references:

Lu D, Chatterjee S, Xiao K, Riedel I, Huang CK, Costa A, Cushman S, Neufeldt D, Rode L, Schmidt A, Juchem M, Leonardy J, Büchler G, Blume J, Gern OL, Kalinke U, Wen Tan WL, Foo R, Vink A, van Laake LW, van der Meer P, Bär C, Thum T. (2022) A circular RNA derived from the insulin receptor locus protects against doxorubicin-induced cardiotoxicity. European Heart Journal, 43(42), 4496–4511. https://doi.org/10.1093/EURHEARTJ/EHAC337

Gupta SK, Garg A, Bär C, Chatterjee S, Foinquinos A, Milting H, Streckfuß-Bömeke K, Fiedler J, Thum T. (2018) Quaking Inhibits Doxorubicin-Mediated Cardiotoxicity Through Regulation of Cardiac Circular RNA Expression. Circulation Research, 122(2), 246–254. https://doi.org/10.1161/CIRCRESAHA.117.311335

Chatterjee S, Hofer T, Costa A, Lu D, Batkai S, Gupta SK, Bolesani E, Zweigerdt R, Megias D, Streckfuss-Bömeke K, Brandenberger C, Thum T, Bär C. (2021) Telomerase therapy attenuates cardiotoxic effects of doxorubicin. Molecular Therapy, 29(4), 1395. https://doi.org/10.1016/J.YMTHE.2020.12.035

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