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

Scientists at the University Medical Center Göttingen found a connection between a reduced expression level of TBX5 and heart failure based on cardiac arrhythmia. The scientists in the group of Prof. Zimmermann were able to develop a gene therapy for the prevention and treatment of a ventricular heart disease and associated complications like cardiac arrhythmia and sudden cardiac death.


More than 60% of all deaths due to cardiovascular disease are represented by out-of-hospital Sudden Cardiac Death (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.
There is still a medical need for new and effective therapeutic applications for the prevention or treatment of cardiac arrhythmia and SCD.

Our Solution

Discovery: 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 (Fig.1).

Fig.1: Low TBX5 expression level in left ventricular biopsies of ICM & DCM patients. NF: Healthy control, DCM: Dilated cardiomyopathies, ICM: Ischemic heart disease. Control expression: CASQ2: Calsequestrin (calcium-binding protein), GAPDH: Glyceraldehyde 3-phosphate dehydrogenase. Source GB1802864.7

Hypothesis: The decreased expression level of TBX5 in ventricular cardiomyocytes, plays an important role in the adult working myocardium.

Investigation: What is the impact of a TBX5 loss for the cardiac function and what is the therapeutic potential of a normalization of the TBX5 level in vTbx5-KO mice.

Outcome: 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 (Fig.2).

Fig.2: TBX5 in vivo re-expression rescues arrhythmia phenotype in ventricular TBX5-KO mouse model. mRNA expression analysis shows physiological re-expression. Statistical analysis shows significantly lower heart rate variability in KO-RE vs KO-CT mice. KO-RE: TBX5 re-expression in vTBX5-KO mice, KO-CT: vTBX5-KO mice control. Source GB1802864.7


  • proof-of-concept experiments show that normalisation of the TBX5 expression level is possible in vivo
  • in vTbx5-KO mice a raise of TBX5 expression levels stabilized heart beat rate
  • the technology allows for a gene-therapie as a prevention and treatment of cardiac arrhythmia


New therapeutic application (e.g. gene therapy) for the prevention or treatment of cardiac arrhythmia and sudden cardiac death by TBX5 re-expression to physiological levels.

Development Status

A proof-of-concept for an AAV-based gene therapy was successfully performed (animal model).

Patent Status

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


Dr. Vanessa Jensen
Patent Manager Life Science
E-Mail: vjensen(at)
Reference: BioC-2092-UMG

Tags: Therapie


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