|Stem Cell Transplants for the Heart Face Uncertainties|
By Nancy Touchette
Doctors treating heart patients are encouraged by studies showing that stem cells can heal the heart and are anxious to move the experimental procedure into the clinic. But United States government officials are concerned about possible risks to patients and are reluctant to permit the procedures without more basic data.
Earlier this year, doctors in Michigan performed an experimental procedure to save the life of a 16-year-old boy who had been injured in a freak accident. The teen had been shot in the heart with an automatic nail gun and suffered a massive heart attack. To prevent further damage to his heart doctors injected him with a concentrated dose of stem cells from his own blood.
The treatment was an apparent success and six months later, Dmitiri Bonneville is attending school and playing basketball with friendsreportedly ignoring his doctors' advice to take it easy.
His doctors feared that without the stem cell transplant, damage would have spread to other areas of the heart and cardiac function would have deteriorated significantly. But tests conducted at his six-month follow-up exam revealed substantial improvement in heart function.
However, shortly after doctors at Beaumont Hospital in Royal Oak, Michigan, announced the results of their treatment, they received a call from an official with the U.S. Food and Drug Administration (FDA).
“After we went public, FDA told us not to conduct any similar procedures,” says Steven Timmis, the cardiologist at Beaumont who performed the bone marrow transplant. “We had also proposed a 100-patient randomized clinical trial, but FDA has denied this.”
The doctors did not seek FDA approval prior to the transplant because it was an emergency operation and they believed the procedure was allowed because the teen received injections of stem cells from his own blood. Transplants of bone marrow, the primary source of stem cells, have been performed routinely in the United States for more than 30 years.
The teenager first received a drug that increases the production of stem cells in the bone marrow. The stem cells are released into the bloodstream. The doctors then collected the cells from his circulating blood.
In 1999, researchers showed that bone marrow stem cells injected into mice with damaged heart muscle homed in to the damaged tissue and restored function. Since then, clinical trials in Britain, Germany, Hong Kong, China, and Brazil have shown that heart patients with heart disease who are injected with their own bone marrow stem cells improve significantly.
However, several studies in animals have raised questions about the safety of such trials because it's not clear whether bone marrow stem cells turn into heart cells or fuse with heart cells to form “hybrid” cells that may pose unknown health risks.
While researchers investigate the mechanisms by which bone marrow stem cells revive heart tissue, clinicians insist that as long as patients are dying, it is critical that these experimental treatments continue.
It is unclear, however, whether such trials will be permitted anytime soon in the United States. An FDA spokesperson would not elaborate on the specifics of the trial proposed by the Michigan doctors but said the agency felt that subjects “would be exposed to a significant and unreasonable risk” and that “insufficient information was submitted to allow FDA to assess the risks.”
Clinical trials can be conducted using living cells without FDA's permission if the trial meets certain conditions. One condition is that the cells being given to a patient perform the same function in the patient as in the donor. This is known as homologous use.
If these conditions are not met, clinicians must apply for permission by submitting an Investigational New Drug (IND) application. In the case of the Michigan proposal, FDA considers the use of stem cells derived from the bone marrow for use in repairing heart tissue to be “non-homologous” even though the cells came from the patient himself.
Timmis and his colleagues complied by submitting an IND to conduct the trial but it was turned down. Timmis says the FDA is concerned, for instance, about the device that delivers the cells to the patient's heart, a balloon catheter used in conjunction with an injection catheter.
Specifically, FDA is concerned about what happens to cells as they travel through the catheter. They are also concerned about how heart tissue might be affected by fluids delivered under pressure through the catheter.
FDA suggested creating an artificial artery to test how cells respond to pressures of five to 10 times greater than those created by a normal infusion. They also requested that the researchers perform animal studies to test the effects of pressure on heart tissue and to determine the optimal dosing of stem cells.
Each of these experiments could require months of work, says Timmis. He notes that many of the suggested studies have been carried out in humans, either in stem cell transfusions in other countries or in tests of catheters routinely used in patients.
“FDA sent us 20 pages in response to our IND application,” says Timmis. “It would take us more than two years to address their concerns and that is just not feasible at this time.”
Timmis and his colleagues are considering all options, including conducting trials in other countries, but he believes this research should also be conducted in the United States.
“There is enormous demand for these types of procedures,” says Timmis. “FDA understands the importance of this work. I think they understand the promise of this work. I hope they also understand the urgency.”
. . .