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Cardium Reports on Presentation at American Heart Association Meeting Relating to Gene Delivery to the Heart and Generx Clinical Development
Date:11/15/2010

peutic benefit of Generx is the effective capture of the Ad5 delivery vector in the coronary micro-circulation, subsequent vector uptake, and FGF-4 protein expression (preferentially in myocytes and endothelial cells). The formation of new blood vessels (angiogenesis) and remodeling of existing collateral vessels (arteriogenesis) are the two main mechanisms contributing to the therapeutic effect of an angiogenic growth factor. New micro-vessel development naturally occurs in the embryo, but in the adult organism it requires tissue injury (such as ischemia) to initiate a regenerative process, including collateral vessel formation.  Research shows that FGF-4 is one of the key regulatory growth-factor proteins that orchestrates micro-vascular and collateral vessel regeneration in the heart.  After the FGF-4 protein is secreted or transported out of the myocyte, it acts via high affinity FGF receptors on neighboring endothelial cells to signal the initiation of cardiac angiogenic activity and enhancement of the arteriogenesis processes.

These actions of FGF-4 are believed to require an ischemic/hypoxic milieu to proceed efficiently.  The structure of the FGF-stimulated vessels may promote stability and produce more mature vessels, which, combined with appropriate blood flow, should contribute to the long term persistence of these newly formed collateral vessels.  Once the beneficial blood vessel growth or vascular remodeling has been accomplished, and provided there is sustained blood flow through the newly-formed vessels, continued FGF-4 growth factor secretion is no longer needed.  Indeed, preclinical studies demonstrated that a single intracoronary infusion of Generx was capable of stimulating new vessel formation in the heart that was associated with improved blood flow and ventricular contractile function, an effect which lasted for at least 3 months.  

About Generx Clinical Development Program Generx (a
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SOURCE Cardium Therapeutics
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