Safety of intracoronary administration of c-myc antisense oligomers after percutaneous transluminal coronary angioplasty (PTCA)

Antisense & Nucleic Acid Drug Development
F RoquéA Zalewski

Abstract

We wished to assess the clinical safety and pharmacokinetics of ascending doses of a synthetic oligodeoxynucleotide (LR-3280) administered after coronary angioplasty. Antisense oligodeoxynucleotides designed to hybridize with target messenger ribonucleic acid (mRNA) in a complementary fashion to inhibit the expression of corresponding protein also have the ability to bind to extracellular growth factors. LR-3280 has been shown to reduce c-myc expression, inhibit growth and collagen biosynthesis in human vascular cells, and reduce neointimal formation in animal models of vascular injury. After successful percutaneous transluminal coronary angioplasty (PTCA), 78 patients were randomized to receive either standard care (n = 26) or standard care and escalating doses of LR-3280 (n = 52) (doses from 1 to 24 mg), administered into target vessel through a guiding catheter. Overall safety was evaluated by clinical adverse events, laboratory tests, and electrocardiograms. Patency was evaluated by quantitative coronary angiography. There were no clinically significant differences between treated and control patients. No adverse effects of LR-3280 on the patency of dilated coronary arteries were observed. Pharmacokinetic data revealed that...Continue Reading

References

Jan 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·S BiroS E Epstein
Jan 15, 1996·Circulation·Y ShiA Zalewski
Feb 18, 1997·Circulation·Y ShiA Zalewski
Mar 1, 1997·Arteriosclerosis, Thrombosis, and Vascular Biology·A Zalewski, Y Shi
Feb 6, 1998·The Journal of Thoracic and Cardiovascular Surgery·J D MannionA Zalewski

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Citations

Apr 6, 2004·Current Opinion in Pharmacology·Ryuichi MorishitaToshio Ogihara
May 9, 2016·The Journal of Allergy and Clinical Immunology·Daniel P PotaczekHarald Renz
Jul 18, 2002·Nature Reviews. Drug Discovery·Joanna B Opalinska, Alan M Gewirtz

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