CDU Contributing Writer

A Canadian physician has developed a device that could replace drug-eluting stents in preventing restenosis or re-narrowing of coronary arteries and help to heal diseased arteries. The first implantation of an antibody-coated stent on a human was performed in May at the Thoraxcentre of the University Hospital Rotterdam (Rotterdam, the Netherlands). It works by promoting the growth of endothelial cells that are destroyed when conventional stents are inserted during angioplasty. Michael Kutryk, MD, of St. Michael's Hospital (Toronto, Ontario) said, "This way works. You implant it and the endothelial covering simply develops."

Drug-eluting stents have lowered the rate of restenosis in patients following cardiac surgery to about 20% and often much less in some trials. The problem, Kutryk says, is that drug-eluting stents also involve the use of "very, very toxic drugs" released locally in high concentration. "It sort of throws an atomic bomb at the site, cleans out everything so that nothing can grow, including the cells that are responsible for preventing restenosis.

"There are many of us who believe that we're going to see a lot of problems down the road with the use of these drug-eluting stents," Kutryk said. "I think they're just going to delay the onset of restenosis and create an even bigger problem in the end." He says the key to eliminating the problem of restenosis altogether lies in a polysaccharide coating on a stent containing an "antibody fragment." The antibody recognizes a receptor on the endothelial progenitor cells circulating in the blood and draws the cells to the surface of the stent. The endothelial cells then bind together to become mature endothelium very soon after the stent is implanted, ensuring the stent remains in place and the underlying artery wall is healthy.

"Endothelial cells are manufacturers of everything that is good to keep restenosis from happening," Kutryk says. "What the antibody-coated stent is trying to do is elicit a natural healing process, to accentuate or contribute to a natural healing process." He began research on the restenosis problem in Holland 10 years ago, working alongside Patrick Serruys, MD, a well-known European cardiologist at University Hospital Rotterdam. In 1996 he shared his idea for antibody stents with Serruys, who thought the idea "sounded interesting," but concluded that "it would never work," Kutryk said. Serruys later surprised Kutryk by asking him to explain his ideas to researchers at a development meeting with a local stent manufacturer. Once again, the idea was greeted with skepticism.

It was only after Kutryk persuaded researchers and biomedical engineers at Orbus Medical Technologies (Fort Lauderdale, Florida) that a smooth endothelial layer could be formed on a stent to eliminate restenosis that the idea began to take off. Orbus helped him to write the patent application, which was filed in 1999, and assisted him in subsequent animal studies.

The next big break occurred shortly before a major cardiovascular clinical meeting last fall. "My technician had run the final defining experiment and he phoned me in the middle of the night and said, 'Michael, you know what, you better buy yourself a bigger house.' I said 'Why?' He said, 'Because the bloody thing works.' So I came down to the hospital and looked at the pictures, and it was amazing how well it worked." Kutryk next presented his findings at last September's Transcatheter Cardiovascular Therapeutics meeting in Washington. The keynote speaker was none other than Serruys, who hailed the antibody-coated stent as one of the most important breakthroughs in interventional cardiology. He reiterated his statement before a videoconference of more than 10,000 interventional cardiologists in May of this year. "If the implantation of the coated stent works in humans like it has in animals, it will be one of the biggest advances in cardiology we have seen to date," Serruys said. "We have been calling Dr. Kutryk's research a glimpse into the future. Today, that future is here."

Kutryk says that chief scientific officers from companies who told him earlier that antibody-coated stents would not reduce restenosis are now paying closer attention to his data. From it, they are learning that new endothelial cells begin forming on a stent implanted into animals almost instantly and that a full endothelial lining is generated in two to four weeks. "Not only did it inhibit restenosis, it prevented stent thrombosis [that is, formation of blood clots] at the stent."

American interventional cardiologists seem impressed by the results, too. Elazer Edelman, MD, a cardiologist at Brigham and Women's Hospital (Boston, Massachusetts) and a pioneer in vascular biology said the "potential Achilles heel" of drug-eluting stents "[is the] active and potentially toxic drug eluting off the stent." Calling Kutryk's data "exciting," Edelman said, "This is a very intellectually appealing approach that combines a firm understanding of the biology of vascular repair and the excitement of cell-based therapies." He added, "We all are eagerly awaiting the results of the clinical trials."

Those clinical trials won't begin until the results of safety trials, now under way in Holland, are completed later this year. European and FDA approvals are projected for some time in 2004.