A radical new treatment for heart attack patients turns out to be wholly ineffective when tested under rigorous conditions, researchers in Germany say in a report that severely undercuts an apparently promising form of stem cell therapy.
Their finding renews a longstanding debate among medical researchers as to whether the basic biology of stem cells needs to be far better understood before testing cell-based therapies in patients is worthwhile.
The new treatment entailed injecting heart attack patients with a hormone that induces the bone marrow to send blood-making cells out into the bloodstream. Experiments with animals had suggested that the blood-making cells would home in on the damaged heart tissue, transform into heart muscle cells and in effect rebuild the heart.
That possibility excited clinicians because the heart has very little capacity to regenerate itself after a heart attack. Instead, it replaces the dead cells with scar tissue that impedes its function.
Another argument for speeding the therapy into clinical trials was that the marrow-stimulating hormone, GCSF, is known to be well tolerated because it is routinely used to harvest a patient's cells in bone marrow transplantation.
In several tests of the GCSF approach on small groups of patients, doctors had reported that heart performance was improved, suggesting that the therapy was working. It seemed that a novel treatment for heart disease would be the first fruit of the new wave of interest in stem cells.
Such hopes have been set back by the new study, undertaken by Dr. Albert Schömig and colleagues at the German Heart Center in Munich and other clinics in Germany. The test involved a large number of patients, half of whom served as a control group who did not receive the GCSF hormone. The results showed no benefit from the hormone, either in improving heart function or in reducing the size of the scar damage, the German team reports in today's issue of The Journal of the American Medical Association.
One reason that the earlier trials gave misleadingly positive results was faulty design, Dr. Robert A. Kloner, a cardiologist at the University of Southern California, wrote in an accompanying editorial in the journal. Some lacked a control group. As it happens, some heart muscle is often stunned but not damaged in a heart attack, and will gradually regain its function. Without a control group, the natural improvement may be falsely attributed to the treatment, Dr. Kloner said.
He said that "some investigators may be disappointed with these results or may try to find fault with the study." But it was one of the most carefully designed studies so far, he said, and "only with such trials will it be possible to differentiate between the hype often generated by smaller, less well controlled trials and reality."
Still, Dr. Kloner said he "would not consider this to be a major setback for stem cell research," since it was nonetheless just one study and there are other variations of the treatment yet to be tested.
Indeed, there are several other proposed ways of using stem cells to treat heart attacks, based on various types of cell or different ways of applying them. Dr. Dietlind Zohlnhöfer, a member of the German team, said the findings with GCSF did not necessarily mean that none of these other stem cell methods would work.
"But our data do not prompt optimism and are not supportive of the application of stem cell therapy in patients with heart attacks," she said.
The problem is that although stem cells are known to be a key player in nature's system for organizing tissues, the way they do it is largely unknown, so attempts to manipulate the system for therapy are not based on a secure grasp of how the cells are meant to behave.
"We have to understand more about the basic biology of stem cells before going to new clinical trials," Dr. Zohlnhöfer said. For example, researchers need to decide what kinds of stem cell are the most promising and exactly how they bring about any improvement seen in animal tests, whether by secreting hormones that prompt repair or turning into new heart muscle cells. At present, "nobody knows what is happening," Dr. Zohlnhöfer said.
Many of the benefits seen from injecting various kinds of cells into stricken heart muscle over the last 10 years have probably been caused not by true regeneration of the heart but by unexpected side effects like the cell's secretion of hormones, say the authors of a recent review in the journal Circulation. They note that new therapies are seldom understood completely — researchers are still learning new things about aspirin — but add that "excessive zeal to test the latest promising strategy can also be problematic."
