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Treatment of cardiac arrhythmia via re-expression of TBX5 (gene therapy)

Dr Maria Patapia Zafeiriou, University Medical Center Goettingen; Dr Laura Zelarayan, University Medical Center Goettingen; Prof. Wolfram Hubertus Zimmermann, University Medical Center Goettingen

MBM ScienceBridge


More than 60% of all deaths due to cardiovascular disease are represented by out-of-hospital Sudden Cardiac Death (SCD). Thus there is a strong need for new and effective therapeutic applications for the prevention or treatment of cardiac arrhythmia and SCD. The T-box protein 5 (TBX5) is an essential transcription factor for cardiac development, but it remains unclear whether TBX5 in adult ventricular cardiomyocytes might play an overlooked critical role for cardiac homeostasis.


TBX5 protein abundance is significantly lower in left ventricular biopsies of patients with human ischemic heart disease (ICM) and dilated cardiomyopathies (DCM) when compared to non-failing hearts. This lead to the hypothesis that a decreased expression level of TBX5 in ventricular cardiomyocytes, plays an important role in the adult working myocardium.

In mice, a loss of TBX5 expression results in cardiac arrhythmia, causing a lethality of 50% after 150 days. A re-expression of TBX5 is possible by inactivation of endogenous inhibitors like microRNA-10a or by enhancing the expression using e.g. CRISPR-dCas9 expression constructs. Enhancing the expression of TBX5 to physiological levels can be used for prevention or therapeutic treatment of a ventricular heart disease and associated complications such as cardiac arrhythmia and SCD

Commercial Opportunity

The technology allows for a gene-therapie as a prevention and treatment of cardiac arrhythmia

Development Status

A proof-of-concept for an AAV-based gene therapy was successfully performed in a mouse model

Patent Situation

We have filed a priority patent application, giving us the possibility of worldwide licensing (Applicant: Georg- August-Universität Göttingen public law foundation).

Further Reading

1) Bruneau et al. Developmental Biology 211, 100 –108 (1999); Chamber-Specific Cardiac Expression of Tbx5 and Heart Defects in Holt–Oram Syndrome

2) Gilsbach et al. Nature Communicationsvolume 9, Article number: 391 (2018); Distinct epigenetic programs regulate cardiac myocyte development and disease in the human heart in vivo


Treatment of cardiac arrhythmia via re-expression of TBX5 (gene therapy)