Successes of Gene Therapy


An experimental gene therapy used in critically ill heart patients has shown significant potential for restoring blood flow in clogged cardiac vessels, reducing chest pain and enhancing quality of life. These successes, which have been demonstrated in a handful of small research studies so far, are drawing attention to a technique that appears to stimulate growth of new blood vessels. If the results are duplicated in larger studies, gene therapy may one day become an important tool in the fight against coronary artery disease.

Last week, researchers at a medical conference in Anaheim introduced two patients with inoperable heart disease who described how gene therapy helped them recover.

Dick Hooper, a 61-year-old retired airline employee from Escondido, said he “could not walk from here to the back of this room without using two to three shots of nitroglycerin” before agreeing to the experimental procedure in 1999.



Hooper had undergone 17 separate angioplasties--procedures in which a balloon is inflated inside a clogged coronary artery to clear blockages--between 1993 and early 1999. He called himself the “19-stent guy,” referring to the 19 wire mesh coils that had been inserted in his arteries during the various procedures.

During the 1999 experimental procedure, doctors inserted into Hooper’s heart several copies of a gene that attached to the surface of his blood vessels and instructed cells to produce VEGF-2, or vascular enthothelial growth factor, which stimulates the sprouting of new blood vessels. This technique, which scientists sometimes refer to casually as “growing your own bypass,” gets its name because it enables the body to create new pathways for blood to circumvent blockages.

Hooper hasn’t needed nitroglycerin since the procedure, and he has even taken up golf. “To me,” he says, “this is nothing short of a miracle.”

A second patient, 72-year-old Jacque Braswell of La Mirada, said her heart problems, including three heart attacks, began at age 28. By 1999, her arteries were so diseased that she gasped for breath walking from her bedroom to the kitchen: “I felt each night this might be it.”

Since receiving gene therapy in June 1999, she has reduced the number of medications she takes, become pain-free and gone back to an active, independent life.

“I have all this energy. I feel like I’m 20,” Braswell said. Hooper and Braswell spoke at an American Heart Assn. news conference with their doctor, Richard A. Schatz, a cardiologist at the Scripps Clinic in La Jolla.


Schatz said patients report feeling better within a few weeks following gene therapy, as more blood pumps through their hearts and relieves their chest pain. Schatz’s patients were too sick to undergo additional bypass procedures, but he said bypasses remain preferable because they allow patients to get off all their heart medicines.

Hooper and Braswell have shown improvement in several measures, he said. For example, a common yardstick for assessing better heart function is a patient’s ability to exercise on a treadmill for an additional 60 seconds without discomfort. Hooper and Braswell have added several minutes each to their treadmill time, and their pain has disappeared.

Eventually, Schatz believes that gene therapy could be performed during angioplasty in patients whose blood vessels are too small for stents or who are unlikely to benefit from angioplasty.

Such therapy, said Schatz, also could be used in bypass patients when the surgeon is unable to reach all the affected vessels.

Until recently, researchers lacked a comparison group to demonstrate whether patients such as Braswell might have improved without the intervention. Ethically, doctors could not open up the chests of several patients for the purpose of testing the gene therapy on just some of them, so there had been no clinical trials.

However, doctors at the Anaheim conference reported on the first scientifically rigorous trials of gene therapy with VEGF-2 in cardiac patients. In this case, some patients got the gene, others got a saltwater solution, and neither the doctors nor the patients knew who was getting the dummy treatment until after the trial was completed.


What enabled them to do this was a new way of getting the gene into the body. Instead of subjecting patients to invasive surgery, they gave patients local anesthesia and inserted the gene through a catheter snaked into the heart’s left pumping chamber. During a period of about an hour, they injected six small doses of the gene material into the hearts of some patients; the control group got only the saltwater solution.

Among 19 patients with severe angina, 12 (including Hooper) got the actual gene treatment. Eight of them had a significant drop in chest pain; one said the procedure eliminated angina. None of the placebo patients did as well.

The report came from Dr. Douglas W. Losordo, director of the Cardiac Catheterization Laboratories at St. Elizabeth’s Medical Center in Boston.

Schatz reported that electromechanical mapping of study participants showed heart muscle changes indicating more activity as well as shrinkage of the area previously deprived of good blood flow.

“This looks really promising,” said Schatz, while cautioning that the research is still in its early stages. Because the number of patients is still small, he said, “we can’t prove to you this is not the placebo effect,” but he hopes to have that proof when testing resumes.