September 15, 2014
By Karen Weintraub
New York Times
A Miami property manager, break-dancer and former high school wrestler, Mr. Irastorza had recently gained weight as his wife’s third pregnancy progressed. “I kind of got pregnant, too,” he said. During a workout one day, he felt short of breath and insisted that friends rush him to the hospital. Minutes later, his pulse flatlined.
He survived the heart attack, but the scar tissue that resulted cut his heart’s pumping ability by a third. He couldn’t pick up his children. He couldn’t dance. He fell asleep every night wondering if he would wake up in the morning.
Desperation motivated Mr. Irastorza to volunteer for a highly unusual medical research trial: getting stem cells injected directly into his heart.
“I just trusted my doctors and the science behind it, and said, ‘This is my only chance,’ ” he said recently.
Over the last five years, by studying stem cells in lab dishes, test animals and intrepid patients like Mr. Irastorza, researchers have brought the vague, grandiose promises of stem cell therapies closer to reality.
Stem cells broke into the public consciousness in the early 1990s, alluring for their potential to help the body beat back diseases of degeneration like Alzheimer’s, and to grow new parts to treat conditions like spinal cord injuries.
Progress has been slow. The Michael J. Fox Foundation for Parkinson’s Research, an early supporter of stem cell research, pulled much of its financial backing two years ago, saying that it preferred to invest in research that was closer to providing immediate help for Parkinson’s disease patients.
But researchers have been slowly learning how to best use stem cells, what types to use and how to deliver them to the body — findings that are not singularly transformational, but progressive and pragmatic.
As many as 4,500 clinical trials involving stem cells are underway in the United States to treat patients with heart disease, blindness, Parkinson’s, H.I.V., diabetes, blood cancers and spinal cord injuries, among other conditions.
Initial studies suggest that stem cell therapy can be delivered safely, said Dr. Ellen Feigal, senior vice president of research and development at the California Institute of Regenerative Medicine, the state stem cell agency, which has awarded more than $2 billion toward stem cell research since 2006 and is enrolling patients in 10 clinical trials this year.
In addition to continuing safety research, “now what we want to know is: Will it work, and will it be better than what’s already out there?” Dr. Feigal said.
Other hurdles include producing consistent, high-quality therapies, receiving federal approval and persuading insurers to cover the treatments.
Stem cells harvested from an embryo can turn into any of the body’s 200 cell types and, theoretically, live as long as the body does, unlike most cells. The basic idea of therapies using stem cells is simple: Inject them, for example, into a brain whose cells are dying, and replacement cells could presumably grow. The same would hold true for muscles, blood, organs and bone. In theory, stem cells can make repairs, lead to new growth and replace missing pieces.
But enthusiasm for stem cells sometimes outstrips the science. When Gov. Rick Perry of Texas had adult stem cells injected into his spine in 2011 for a back injury, his surgeon had never tried the procedure and had no data to support the experiment. A June review in The New England Journal of Medicine found that “platelet-rich plasma” stem cell therapies praised by a number of athletes worked no better than placebos.
And there’s no evidence that podiatrists promising better bunion care, dermatologists offering smoother skin or overseas medical spas peddling miracle cures are doing anything but putting patients at risk.
Such public chatter may imply that stem cell research is further advanced than it is, said Dr. Charles Murry, a co-director of the Institute for Stem Cell and Regenerative Medicine at the University of Washington.
Slick websites advertising stem cell therapies leave the impression that such treatments are ready to use and that “the only problem is the evil physicians and government, who want to separate people from lifesaving therapies,” said Dr. Murry, a cardiovascular pathologist.
There is much hope and enthusiasm behind stem cell therapy. However, the science still has catching up to do. David Corcoran and Jeffery DelViscio
In fact, very few therapies beyond bone marrow transplants have been shown to be effective, he said. “Almost every one of these places are charlatans.”
Truth stretching happens in the lab, too.
This year researchers at the Harvard-affiliated Brigham and Women’s Hospital in Boston, working with Japanese scientists, announced a breakthrough in the creation of powerful stem cells using a simple acid bath. But months later, amid allegations of scientific misconduct, the journal Nature retracted their papers. Questions were also raised about another Brigham stem cell researcher; the journal Circulation withdrew one of his papers, and The Lancet wrote an “expression of concern” about another paper by him.
“Nothing other than people’s skepticism can protect them” from the misuse of science, said Dr. David Scadden, a co-director of the Harvard Stem Cell Institute and an oncologist at Massachusetts General Hospital. “That’s true for any emerging technology of great potential; it will have its dark side.”
In 2001, President George W. Bush prohibited the use of federal funds to create new embryonic stem cell lines. At the time, destroying embryos was the only viable way to create stem cells, stimulating vigorous debate about the ethics of developing treatments with them.
In 2006, the Japanese researcher Shinya Yamanaka, who later won a Nobel Prize, discovered a way to turn adult cells back into stem cells. Today, scientists still use embryonic stem cells, which are considered the standard against which other stem cells are measured. But the field is much less dependent on them.
Understanding how stem cells work requires some basic biology.
Every cell in the body has the same set of DNA, although different genetic material may be active in, say, a nerve cell and a blood cell. Embryonic stem cells, derived from the first cells created after conception, can live as long as the body does, with the potential to make every other cell type in the body.
If the embryonic stem cell is at the top of every cell’s family tree, the first branches are different kinds of stem cells, like those that give rise to all blood, muscle or brain cells. Below those are even more restricted precursor cells — parents of all heart cells, for example.
Dr. Yamanaka’s cocktail allows researchers to reverse that progression, for instance turning a skin cell back into what’s called an induced pluripotent stem cell. Now, researchers can move the reverted cell forward, too, making, say, a precursor cell to inject into a beating heart.
But figuring out which type of cell best addresses a particular medical condition remains a major research challenge. For instance, injecting embryonic stem cells into a patient might solve the problem, might do nothing, or might seed a tumor called a teratoma. And it may be years before the outcome is obvious, as in the case of a paraplegic American woman who had stem cells from her nose implanted into her spine as part of a clinical trial in Portugal. The therapy failed, and eight years later, the woman had a tumorlike mass of nasal tissue surgically removed from the implant site, researchers reported this summer. Last week, cells created using Dr. Yamanaka’s method were tested in a person for the first time.
Developing human embryos that could be used to harvest stem cells. Credit Reuters
Kevin Eggan, also with the Harvard Stem Cell Institute, uses the technique to study amyotrophic lateral sclerosis, or Lou Gehrig’s disease. Five years ago, he took skin cells from two women dying from the same genetic form of A.L.S. He turned these skin cells into stem cells and then into nerve cells, and noticed an electrical problem: The cells weren’t signaling to one another properly, which was probably causing the neural degeneration that characterizes A.L.S.
He replicated these nerve cells thousands of times and then tested thousands of drug compounds to see which would correct the electrical signaling problem. He found a candidate drug — an existing medication approved for epilepsy — that will be tested in A.L.S. patients as soon as the end of this year.
To be sure, a neuron in a dish is a far simpler thing than a disease in humans, with our many trillions of cells and interwoven systems.
“Part of the study is to now see whether the drug we discovered changes the same electrical problem in the intact patient” as it does in a nerve cell in a dish, Dr. Eggan said.
The whole process, he said, “is something that’s never been remotely possible before.”
Still to be determined is the most cost-effective way to deliver stem cells.
Scientists presumed, for instance, that a patient’s heart would repair itself better when injected with its own stem cells. But the study that Mr. Irastorza volunteered for at the University of Miami showed that patients fared just as well with someone else’s stem cells, and their bodies didn’t mount an immune attack against the cells. If supported by further studies, this means that future patients won’t need immune suppressants, and that stem cells can be made in large batches — and therefore more cheaply.
“That’s incredibly important, because that means off-the-shelf therapy is possible,” said Joshua Hare, founding director of the University of Miami’s Interdisciplinary Stem Cell Institute, who led the research trial.
Treatment for Mr. Irastorza, who received his own cells, began with the withdrawing of some of his bone marrow. Researchers took adult cells believed to be stem cells from the marrow and then inserted them through a catheter directly into Mr. Irastorza’s heart.
About a third of his left ventricle had been destroyed by his heart attack, which was attributed to a hereditary cholesterol problem. It’s impossible to know for sure whether the bone marrow cells’ descendants became heart muscle cells or if repairs were spurred some other way, but today, his doctors tell him his heart is one-third of the way back to normal.
It’s enough, Mr. Irastorza said, to allow him to dance again and to be the kind of father he wants to be: “My quality of life is like night and day to before the treatment.”
Why, then, are there not more success stories, given all the money poured into stem cell research?
“Progress comes in fits and starts,” said Dr. Scadden, of the Harvard Stem Cell Institute, comparing the halting advances in the field to the “war on cancer” declared in 1971.
“No one would say it has fully delivered, but many thousands are alive today because of it and the smaller-scale, very real triumphs along the way. And those triumphs increase with every year,” he said. Using stem cells to routinely treat disease “will take time, but when we look back 20 years from now, I think medicine and human health will be transformed by it.”