FDA Holds Up Work on Transplanted Stem Cells

FDA Holds Up Hospital's Work
With Transplanted Stem Cells

By ANTONIO REGALADO
Staff Reporter of THE WALL STREET JOURNAL


A Michigan boy who received a pioneering stem-cell transplant in February after suffering a heart attack has made a strong recovery -- but federal regulators have warned his doctors not to do more experiments.

Officials at Beaumont Hospital in Royal Oak, Mich., disclosed their attempt to repair the heart of 16-year-old Dimitri Bonnville at a news conference in March. Citing research done in animals and overseas, the hospital's cardiologists said they had collected bone-marrow stem cells from the boy's bloodstream and transfused them into his heart, hoping to regenerate the damaged muscle.

The disclosure brought an immediate inquiry from the Food and Drug Administration. Last month, it turned down the hospital's request to try the transplant in 400 more patients, citing inadequate evidence that the treatment is safe and likely to help.

An FDA representative said the agency doesn't comment on applications to test new treatments. However, the agency has asserted its regulatory authority in cases where cells are manipulated outside the body, as well as in cases where cells are being injected into a different organ from the one where they were drawn.

The regulatory step comes amid increasing enthusiasm by heart experts that cell transplants could help patients recovering from heart attacks or suffering from chronic heart disease. The move is a sign of the agency's caution over politically charged stem-cell research, particularly in the wake of devastating side effects and deaths seen in gene-therapy treatments.

Executives at several companies developing stem-cell treatments said they viewed the regulatory move as prudent. The stem-cell field is beset by scientific uncertainties, and some leading laboratory biologists said the science underpinning the Beaumont experiment is shaky.

For a decade, a relatively small number of corporate chiefs, scientists and regulators have shaped the development of so-called cell therapy. An exciting but contradictory flood of new data on stem cells recently has rocked conventional thinking in the field. As a result, regulators "are feeling their way on this stuff," says Duke Collier, executive vice president of Genzyme Corp. "No one knows what is going on, there are hundreds of papers being published, and I think the FDA is reading them carefully, as are we."

Such concerns have made regulators in Washington more cautious. One result: Much of the human research is being conducted overseas. "It's been easier to move more rapidly in other countries," says James Willerson, director of the Texas Heart Institute in Houston. Dr. Willerson recently co-wrote a study of bone-marrow cells injected into the hearts of 14 people, all in Brazil, but hopes to launch a larger study in Texas.

Companies say the problem isn't foot-dragging by the FDA, but rather a collision between physicians pursuing new treatments and regulators seeking to understand their risks. Martin McGlynn, chief executive of StemCells Inc., a Palo Alto, Calif., biotech concern, says FDA staff, realizing that some medical schools have been involved in unregulated studies, are sending "shots across the bows" of some hospitals.

Scientists are studying different types of cells as heart treatments, and several biotech companies have launched tests of leg-muscle cells, a more conventional approach.

Studies have indicated that stem cells, despite the fact that they are derived from bone marrow, may also form heart muscle. But those results have been questioned by other biologists as unpersuasive. Researchers in the laboratory of Irving Weissman, a top biologist at Stanford University, say they found no sign of new muscle cells in rodents treated with purified bone marrow stem cells.

Beaumont didn't think it needed regulatory approval for its stem-cell work, says head cardiologist William O'Neill, because bone-marrow transplants are used widely to treat cancer patients, and in that case aren't regulated by the FDA. Plus, the cells hadn't been altered and weren't being used commercially, he adds.

The patient, Mr. Bonnville, was shot in the heart with a nail gun on a construction site. After doctors removed a nail from his heart, he had a heart attack that destroyed a third of its muscle cells. Doctors decided to try the stem-cell transplant after concluding his condition would worsen over time, eventually requiring a heart transplant.

The day after doctors disclosed the experiment, the FDA started an inquiry. Last month, the agency provided 20 pages of comments and asked the hospital to conduct animal studies before proceeding with further human procedures. Beaumont abandoned the experiment because its doctors said they cannot satisfy the FDA's requirements.

Meanwhile, the doctors say the treatment appears to have worked. Mr. Bonnville's heart is ejecting about 40% of its contents with each beat, up from 25% after his heart attack. A young person typically ejects about 60% per beat. The teen "plays basketball with his pals," says his main doctor, Steven Timmis.

Still, it's uncertain whether the stem-cell treatment is responsible, because cardiologists rarely treat heart attacks in patients so young, Dr. O'Neill says. "But we are optimistic that it did work."

Write to Antonio Regalado at [email protected]

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