July 26, 2012
/PRNewswire/ -- Cardium Therapeutics (NYSE MKT: CXM) today announced the publication of preclinical findings demonstrating that cardiac ischemia plays an important role in adenovector gene delivery (transfection) in mammalian hearts. The new findings were published in the peer-reviewed journal
Human Gene Therapy Methods
in an article entitled "Ischemia-Reperfusion Increases Transfection Efficiency of Intracoronary Adenovirus type 5 in Pig Heart in Situ," which is available online at
The published findings demonstrate that Cardium's innovative technique employing transient cardiac ischemia can be used to dramatically enhance gene delivery and transfection efficiency after one-time intracoronary administration of adenovector in mammalian hearts. Two consecutive but brief periods of coronary artery occlusion combined with co-administration of nitroglycerin increased both adenovector presence (measured by PCR) and transgene expression (assessed by luciferase activity) by over two orders of magnitude (>100 fold) in the heart, as compared to prior intracoronary artery delivery methods.
"The clinical success of DNA-based therapies can be enhanced by employing optimized gene delivery methods," stated Dr. Gabor M. Rubanyi, Cardium's Chief Scientific Officer and co-author of the published paper. "In addition, data analysis from the AGENT 1 through 4 clinical studies, involving more than 650 patients in Phase 1/2 through Phase 2/3, showed that patients with more severe forms of coronary artery disease – which is associated with increased ischemia – tended to be more responsive to the one-time administration of Generx than patients with less severe disease. The research results published in
Human Gene Therapy Methods
extend those findings and demonstrate that Cardium's new technique for adenovector gene delivery in the heart can be used to dramatically boost adenovector delivery. By enhancing uptake even in patients with less severe forms of disease and ischemia, it would be expected to reduce response variability and allow for the potential treatment of patients with a broader range of associated coronary artery disease. The new treatment protocols for Cardium's recently-initiated ASPIRE clinical study have been developed to use our knowledge about induced transient ischemia techniques to leverage these research findings and enhance the non-surgical, catheter-based delivery of Generx to the heart," stated Dr. Rubanyi.
Cardium's new method of adenovector delivery to the heart takes advantage of the fact that transient ischemia may reduce the permeability barrier of the vascular endothelium and may increase the number of available coxsackie-adenovirus receptors mediating adenovector uptake. Balloon angioplasty catheters have been used for many years to dilate blocked coronary arteries, sometimes with use of a stent, and these catheters have also been used safely by cardiologists in patients with coronary artery disease to study the effects of brief ischemia. Cardium's new technique inflates the balloon in non-narrowed coronary artery areas, just enough to briefly interrupt flow using inflation pressure that is significantly less than that used for performing routine angioplasty procedures.