NEW YORK (Reuters Health) - Intracoronary administration of adenovirus containing a gene encoding fibroblast growth factor (Ad5FGF-4) appears to improve myocardial perfusion in patients with stable angina, members of the Angiogenic GENe Therapy (AGENT-2) Study Group report.
The study group previously found that Ad5FGF-4 therapy resulted in increased treadmill exercise time in patients with stable angina. “But we did not directly measure blood flow in the heart to prove we were growing new collaterals,” lead investigator Dr. Cindy L. Grines told Reuters Health.
Therefore, AGENT-2, a randomized, double-blind study, was designed to directly measure myocardial perfusion after Ad5FGF-4 treatment using SPECT imaging. The results are published in the Journal of the American College of Cardiology for October 15.
Included in the study were 52 patients with stable angina resistant to anti-anginal drugs who were not good candidates for revascularization. Adenosine-induced ischemic left ventricular perfusion defect size averaged 20%. Thirty-five subjects underwent Ad5FGF-4 treatment and 17 received placebo treatment.
“The method of administration, intracoronary infusion, is a standard cauterization technique,” Dr. Grines noted.
Eight weeks later, Ad5FGF-4 treatment was associated with a 4.2% reduction in reversible perfusion defect size, compared with a 1.6% reduction in the placebo group, the report indicates. After excluding from analysis one placebo group subject who did not comply with anti-anginal therapy in the pre-treatment period, differences between groups were significant at 4 weeks (p = 0.01) and at 8 weeks (p < 0.05).
Moreover, increased ischemic defect size was observed in significantly fewer patients who underwent gene therapy, 6% versus 35%. There was a trend toward greater symptomatic improvement in the active treatment group compared with the control group, with 43% and 17% of subjects, respectively, no longer using nitroglycerin at 8 weeks post-treatment.
During follow-up for up to 1 year, “Ad5FGF-4 was well tolerated and did not result in any permanent adverse sequelae,” the authors add.
Based on these promising findings, Dr. Grines said, the AGENT-3 and AGENT-4 trials are currently enrolling 450 patients each to gather more information regarding long-term outcomes of Ad5FGF-4 gene therapy.
Source: J Am Coll Cardiol 2003;42:1339-1347. [ Google search on this article ]
MeSH Headings:Biological Therapy: Genetic Engineering: Genetic Techniques: Investigative Techniques: Therapeutics: Gene Therapy: Analytical, Diagnostic and Therapeutic Techniques and EquipmentCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
