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Updated: Aug 10, 2026
In Vivo Gene Transfer to the Rabbit Common Carotid Artery Endothelium
Published on: May 6, 2018
Gene therapy with vascular endothelial growth factor for inoperable coronary artery disease
J F Symes1, D W Losordo, P R Vale
1Department of Surgery, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA. jsymes@semc.org
Insights
Gene therapy using plasmid vascular endothelial growth factor (ph-VEGF165) safely improved symptoms in patients with inoperable coronary artery disease. The treatment reduced angina and improved heart function, offering a new therapeutic option.
Area of Science:
- Cardiovascular Medicine
- Gene Therapy
- Regenerative Medicine
Background:
- Patients with intractable angina and prior revascularization are often deemed inoperable.
- Diffuse distal disease or lack of conduits contributes to inoperability.
- A phase I trial assessed intramyocardial plasmid vascular endothelial growth factor (ph-VEGF165) gene transfer.
Purpose of the Study:
- To evaluate the safety and bioactivity of intramyocardial ph-VEGF165 gene transfer.
- To assess the efficacy of this novel therapy in patients with inoperable coronary artery disease.
Main Methods:
- Twenty patients with class III/IV angina and inoperable coronary artery disease received phVEGF165 (125 or 250 microg) via mini-thoracotomy.
- The procedure was performed as sole therapy.
- Safety, plasma VEGF levels, angina symptoms, and perfusion scans were monitored.
Main Results:
- The procedure was well-tolerated with no perioperative complications.
- Plasma VEGF levels significantly increased post-treatment.
- Significant reduction in angina frequency and nitroglycerin use was observed.
- Improved perfusion defects and collateral filling were noted on imaging.
Conclusions:
- Direct myocardial gene transfer with phVEGF165 is safe in patients with inoperable coronary artery disease.
- The therapy may lead to significant symptomatic improvement.
- This approach offers a potential new treatment strategy for refractory angina.
Background:
Patients presenting with medically intractable angina who have undergone previous coronary bypass (CABG) and/or percutaneous revascularization procedures are frequently deemed "inoperable" based on angiographic findings of diffuse distal disease or a lack of available conduits. We initiated a phase I clinical trial to assess the safety and bioactivity of intramyocardial transfection of plasmid DNA encoding for the angiogenic mitogen vascular endothelial growth factor (ph-VEGF165) in such patients.
Methods:
phVEGF165 (125 microg, n = 10; 250 microg, n = 10) was injected directly into the myocardium through a mini left anterior thoracotomy as sole therapy in 20 patients (15 male, 5 female, age 48 to 74 years) with class III or IV angina, reversible ischemia on stress sestamibi scans, and "inoperable" coronary artery disease.
Results:
All patients tolerated surgery uneventfully and were extubated on the table. No perioperative myocardial infarction, hemodynamic instability, or change in ventricular function occurred. Mean hospital stay was 3.9 days. There was one late death (4 months). Plasma VEGF protein level increased from 30.6+/-4.1 pg/mL pretreatment to 73.7+/-10.1 pg/mL 14 days posttreatment (p = 0.0002) and returned to baseline by day 90. All 16 patients followed to day 90 reported a reduction in angina (nitroglycerin use/week = 60.2+/-4.9 preop vs 3.5+/-1.6 at 90 days; p<0.0001). Seventy percent (7 of 10) patients were completely angina free at 6 months. A reduction in ischemic defects on single photon emission computerized tomography sestamibi scans was observed in 13 of 17 patients at 60 days (7 of 8 in the 250-microg group). Stress perfusion score decreased from 19.4+/-3.7 at baseline to 15.9+/-3.4 at 60 days (p = 0.025). Angiographic evidence of improved collateral filling of at least one occluded vessel was observed in all patients evaluated at day 60.
Conclusions:
Direct myocardial gene transfer with phVEGF165 via a mini-thoracotomy can be performed safely and may result in significant symptomatic improvement in patients with "inoperable" coronary artery disease.
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