Celladon’s drugs act upon the Sarcoplasmic Reticulum ATPase2a (SERCA2a) pump, the central control point for progression of heart failure. Treatments targeting this pathway essentially reversed the deterioration in cardiac function in experimental models. Furthermore, the therapeutic agents were delivered using delivery methodologies easily translated into clinical procedures for human heart failure, which are similar to how coronary angioplasty is performed.
The ovine model of pacing induced heart failure used in the study induces moderate to severe heart failure, lowering ventricular ejection to a similar level experienced by humans. Once the animals were treated with the SERCA2a gene they experienced restored levels of ventricular ejection.
The SERCA2a gene not only induced short term improvement, but by using adeno-associated vectors (AAV) targeted to the heart, provided long-term gains in ventricular function indices following gene transfer of SERCA2a.
Speaking of the trials, Dr Krisztina Zsebo, president of Celladon said: “These large animal studies by Celladon’s collaborators, indicate that AAV agents targeting this pathway can reverse the progression of congestive heart failure. Gene delivery may provide a new approach to unlocking the therapeutic potential of this pathway, whereas previous traditional small molecule attempts have not been successful. These results will pave the way for the first clinical trial of gene therapy for heart failure using AAV vectors.”
Celladon plans to initiate human trials with this agent in 2006.