Gene therapy with phosphodiesterases to treat heart failure


  Rodolphe Fischmeister
INSERM and University Paris-Sud, Paris, France

Viacheslav Nikolaev, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Finn Olav Levy, University of Oslo, Oslo, Norway
Emilio Hirsch, University of Torino, Torino, Italy

Research focus:
In heart failure (HF) patients, the heart is unable to meet the hemodynamic needs, such as during a physical exercise or an emotional stress. The sympathetic nervous system, activated upon exercise or stress acts on the heart by the release of noradrenaline which activates beta-adrenergic receptors. Once activated, these receptors cause the production of cyclic AMP (cAMP). However, when the body demand stops, the heart returns to its normal activity by a family of enzymes called phosphodiesterases (PDEs). Thus, beta-adrenergic receptors serve as an accelerator and PDEs as a brake. In HF, the accelerator pedal is stuck to the floor and the brakes are ineffective. This project will use a new gene therapy approach to reintroduce different defective/missing types of PDEs into the heart, with the hope to prevent the associated heart rhythm disorders which are the main cause of death in HF.