Local gene therapy improves myocardial blood flow in refractory angina patients

Milly Dawson | | Cardiovascular Business | Acute Coronary Syndromes

For the first time, researchers have employed local gene therapy to boost myocardial blood flow in areas that have impaired perfusion reserves. They have also determined that elevated plasma Lp(a) can serve as a biomarker to identify those individuals with refractory angina (RA) who can benefit from the experimental therapy, gene transfer of VEGF-DΔNΔC.

“NOGA catheter-mediated intramyocardial delivery of Ad VEGF-D ΔNΔC was safe and well tolerated and may offer a new option for the treatment of RA,” the researchers wrote.

Led by Juha Hartikainen, with the Heart Center at Kuopio University Hospital in Kuopio, Finland, the team’s work was published online July 31 in the European Heart Journal.

Although medical and revascularization therapies have improved in recent years, 5 to 10 percent of patients who undergo coronary angiography have RA. After revascularization, they continue to be severely symptomatic in spite of prior revascularization and today’s best medical treatment.

Therapeutic vascular growth can stimulate the development of collateral arteries, which in turn can rescue myocardium despite serious blockages in coronary arteries and alleviate symptoms.

“However most previous cardiovascular proangiogenic trials have been unsuccessful,” the researchers wrote.

Thirty patients with severe RA were randomized to receive either treatment with VEGF-DΔNΔC or to a placebo/control group.  The study’s main finding was that intramyocardial AdVEGF-DΔNΔC gene therapy was safe, feasible and well tolerated. 

Benefits appear to be long term. Myocardial perfusion increased in the treat patients at both 3 and 12 months. 

“To our knowledge, this is the first time that treatment aimed to cause vascular growth shows an objective long-term improvement in myocardial perfusion in the treated areas,” the authors wrote.

Furthermore, quality of life improved for treated patients. A clinically meaningful change in their 15D scores was observed at 3 months. In contrast, after three months, 15D scores for patients in the control group showed no statistical or clinically meaningful shifts.

Looking ahead, Phase IIb/III trials are needed to confirm the study’s findings regarding the safety and efficacy of gene therapy in RA patients.

Milly Dawson

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