Embryonic stem cells, from a woman with Type 1 diabetes, were induced to turn into insulin-making beta cells, in hopes they could be implanted to cure the disease. SEPT. 15, 2014
Edgar Irastorza was just 31 when his heart stopped beating in October 2008.
Edgar Irastorza was just 31 when his heart stopped beating in October 2008.
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.
Edgar Irastorza, who had
stem cells injected into
his heart after a major heart attack, was
break-dancing
again a few years after the procedure.
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.
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.
Beyond direct therapies, stem cells are also giving researchers new tools in the lab. Using cells created from patients with specific ailments, it’s possible to reproduce and study diseases in a dish. |
| Developing human embryos that could be used to harvest stem cells. 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.”
Correction: September 18, 2014
An earlier version of this article
misstated federal policy concerning research on embryonic stem cell lines. In
2001, President George W. Bush prohibited the use of federal research funds to
create new embryonic stem cell lines. He did not prohibit all creation of new
embryonic stem cell lines. (Privately funded research at the time was
unaffected and President Obama later lifted the ban in 2009). The article also
referred imprecisely to the approach of The Michael J. Fox Foundation for
Parkinson’s Research toward stem cell research. While the majority of the
foundation’s current funding is in other areas of research, it has not stopped
funding stem cell research.
A version of this article appears in print on September
16, 2014, on page D1 of the New York edition with the headline: The Trials of
Stem Cell Therapy.
http://www.nytimes.com/2014/09/16/science/stem-cell-progress-begins-to-catch-up-to-promise.html?_r=0
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