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Intramural coronary delivery of advanced antisense oligonucleotides reduces neointimal formation in the porcine stent restenosis model

Nicholas N. Kipshidze, MD, PhD, FACC^*,*, Han-Soo Kim, MD, FACC, Patrick Iversen, PhD, Hamid A. Yazdi, MD, Balram Bhargava, MD, Gishel New, MD, FACC^*, Roxana Mehran, MD, FACC^*, Fermin Tio, MD, Christian Haudenschild, MD^||, George Dangas, MD, PhD, FACC^*, Gregg W. Stone, MD, FACC^*, Sriram Iyer, MD, FACC^*, Gary S. Roubin, MD, PhD, FACC^*, Martin B. Leon, MD, FACC^* and Jeffrey W. Moses, MD, FACC^*

^* Lenox Hill Heart and Vascular Institute and Cardiovascular Research Foundation, New York, New York, USA
Cardiology Research Institute, Washington, DC, USA
AVI BioPharma, Portland, Oregon, USA
Biomedical Research Foundation of South Texas, San Antonio, Texas, USA
^|| American Red Cross, Jerome Holland Laboratories, Rockville, Maryland, USA

View larger version (59K): [in a new window]   Figure 1 Data from Western blot analysis of porcine coronary arteries for c-myc and actin protein expression. Two hours following: (1) Stent; (2) Stent + 0.5 mg Resten-NG; (3) Stent + 1.0 mg Resten-NG; (4) Stent + 3.0 mg Resten-NG; (5) Stent + 5.0 mg Resten-NG.

View larger version (158K): [in a new window]   Figure 2 Cross-section samples of the control and the three dosage groups showing area percent stenosis of 69%, 45%, 32% and 25%, respectively (Metachromatic stain, Original magnification s.09X).

View larger version (22K): [in a new window]   Figure 3 Regression analysis between injury score and intimal area. The significant decrease in slope between treated and control groups indicates that local delivery of antisense results in significantly less intimal growth despite similar degrees of arterial injury. Each data point represents a single treated arterial segment.