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Behandlung von Herzrhythmusstörungen mittels TBX5-Re-expression (Gentherapie)

Ref-Nr: TA-MBM-BioC-2092-UMG


Kurzfassung

Herz-Kreislauf-Erkrankungen sind weltweit die häufigste Todesursache. Wissenschaftler des Universitätsklinikums Göttingen entwickelten eine Gentherapie (TBX5-Re-expression) zur Prävention oder Therapie einer ventrikulären Herzerkrankung und den damit verbundenen Komplikationen wie Herzrhythmusstörungen und plötzlicher Herztod. Details


Hintergrund

Scientists at the University Medical Center Göttingen developed an expression construct capable of enhancing expression of TBX5 in a subject to be treated, for use in the prevention or therapeutic treatment of a ventricular heart disease and associated complications selected from cardiac arrhythmia and sudden cardiac death.


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Problemstellung

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.


Lösung

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).

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).


Vorteile

  • 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

 

 


Anwendungsbereiche

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.


MBM ScienceBridge GmbH

Dr. Martin Andresen
0551-30724 150
mandresen@sciencebridge.de
www.sciencebridge.de
Adresse
Hans-Adolf-Krebs-Weg 1
37077 Göttingen



Entwicklungsstand

Präklinik


Patentsituation

  • EP GB1802864.7 anhängig

Stichworte

MBM ScienceBridge GmbH, Technologieangebot, Technologietransfer, Georg-August-Universität Göttingen, Universitätsmedizin Göttingen, Zimmermann, Zafeiriou, MBM ScienceBridge GmbH, Technologieangebot, Technologietransfer, Georg-August-Universität Göttingen, Universitätsmedizin Göttingen, Zimmermann, Zafeiriou

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