cell therapy may be fatal
By Peter Gorner
Tribune science reporter
Published June 4, 2002
Three years ago, Justin Sears was a carefree college
student whose hands mysteriously started to shake when he tried to use his
The tremors were sporadic at first, but grew increasingly severe. He tried
to ignore what was happening to his hands, but he soon started having
trouble with his balance. Before long, he couldn't even climb stairs.
He was diagnosed with multiple sclerosis (MS), a chronic, neurological
disorder that affects 350,000 Americans and is characterized by damage to
the nerves in the brain and spinal cord that becomes worse over time,
leading to spasticity or paralysis of muscles.
But his disease seems to have been put on hold, thanks to a new and
controversial stem cell therapy that he received at Northwestern Memorial
Over the last 20 years, the transplantation of bone marrow stem cells
revolutionized the treatment of leukemias and other cancers.
The revolution is gradually moving to autoimmune disorders such as
multiple sclerosis, lupus, rheumatoid arthritis and Crohn's disease. But
with that promise comes a cost: The stem cell therapy can be fatal, while
MS rarely is.
Stem cells, the master cells that make blood, are retrieved from a
patient's bloodstream before therapy and then returned to the same
patient, a process known as autologous transplantation.
Although stem cells are found in larger numbers in bone marrow, removal
from the bloodstream is easier, less costly and does not require general
anesthesia. When re-infused into the bloodstream, they migrate into the
bone marrow and--if the therapy is successful--produce a new immune
Such transplants demonstrate the regenerative behavior of stem
cells--either from a stranger or from oneself--and their power to heal.
They provide most of the hard evidence behind the stem cell revolution
that has swept through science and is being debated in Congress and in
Now 25, Sears, of the South Side, is back studying psychology at Moraine
Valley Community College in Palos Hills. His symptoms have subsided. His
future looks much brighter.
"I can write with a pen again," he said, ticking off the improvements.
"The hand tremors are much better. I can butter my own bread and eat soup,
which I couldn't do before. I can climb stairs again.
"Before, I couldn't walk a hundred feet. Now, I can walk for miles."
Nobody knows what causes MS, but it seems triggered when the body becomes
allergic to itself and the misdirected immune system attacks the central
nervous system--specifically, the myelin sheaths, the thin layers of fatty
cells that wrap around and insulate nerve fibers of the brain and spinal
Repeated attacks bring about a loss of the protective coating of myelin,
which halts nerve cells from communicating much the way that frayed
electrical wires short out and stop carrying current. MS is a crippler,
not usually a killer, but the progression of the disease cannot be
predicted and depends on the individual.
Northwestern Memorial has pioneered stem cell transplants for this and
other devastating neurological disorders. Dr. Richard K. Burt, the
hospital's director of immunotherapy, performed the first procedure in the
U.S. in 1997. Based on the program's success so far, the National
Institute of Allergy and Infectious Diseases awarded the hospital a $9.2
million contract for further research on stem cell transplants for
Sears received his transplant in January 2001. After doctors removed stem
cells from his own blood, they killed his immune system, which had turned
into a renegade, and then returned the healthy bloodmaking cells to his
The cells set up shop and built a new immune system that didn't attack his
Sears was hospitalized for three weeks. The transplant cost $85,000, and
Medicaid paid. If resetting the young man's immune system stops further
damage from MS, the long-term costs of the disease would make stem cell
transplants a bargain.
Sears' initial diagnosis, frightening as it was, was confounded even more
because specialists could not predict what would happen to him.
Symptoms of MS may be mild--numbness or weakness in the limbs, blurred
vision, clumsiness--or severe, such as paralysis, loss of intellect,
blindness. About 70 percent of patients experience problems sporadically
over several years--the "relapsing-remitting" form of the disease--but in
others it progresses rapidly, leaving them bedridden, confined to a
wheelchair or dead within 10 years.
Faced with such uncertainties, the MS research community is conservative
and suspicious of any new therapy.
Studies of stem cell transplants for MS have involved small groups of
severely disabled patients at research hospitals, and the evidence is
mounting that the new treatment is safe. Trials are getting under way to
test its efficacy and compare that to accepted treatments.
Researchers, like Northwestern's Burt, worry about raising false hopes.
"We recently completed our study of 29 patients, and in most of them the
tests suggested no further loss of myelin," he said. "We seem to be
holding the disease in check.
"On the other hand, despite the transplant, some of our more severely
disabled patients continued to deteriorate. We may have stopped the
further loss of myelin, but for them it didn't seem to matter.
"I think when people reach that point, there's something else going on. MS
may actually be two diseases. When too many nerve cells have been
destroyed, our stem cell therapy is like closing the barn door after the
horse has left."
Doing the transplant earlier, though, brings a formidable ethical problem.
"We want to do this in people who are having acute attacks, before the
long-term damage can accumulate," Burt said. "But this is a very dramatic,
potential life-threatening therapy. And we'd be doing it on patients who
otherwise might do well on ordinary treatment.
"Bone marrow transplants are ethical in cancer, which is a fatal disease.
But MS rarely is fatal. So the ethics here are really tricky."
The Northwestern Memorial results fall in line with those reported by
other institutions, where as many as 85 percent of transplanted MS
patients seem to be doing better.
"Preventing people with MS from becoming disabled--that's the goal," Burt
said. "No other therapy has done that. But it's still too early to say if
stem cell transplants can prevent disability."
One of the first patients in the world to have the transplant before she
was physically disabled was Air Force Capt. Deb Strand, a critical care
nurse, who lives near Olympia, Wash.
"Because of MS, my life went to hell in a year and a half," she said. "I
lost my job, my career, my nursing license--I had cognitive problems,
started to stutter and couldn't remember patients. My IQ dropped from 130
in college to 87. I had to retire from the military."
She did research on the Internet, discovered Burt and came to Northwestern
Memorial in July 2000. Her transplant was on Aug. 11--"that's when I
celebrate my birthday," she said. "That's the day my new life began."
She still has problems, she admits.
"But nothing has progressed. Nothing has gotten worse. The transplant is
not a cure-all; it's not like my MS has gone away. I still have short-term
memory problems, but I can cope with them.
"I have stability in my life. I'm not in limbo-land any longer."
Doctors have known for 50 years that suppressing the immune system can
slow the progression of MS, but the tradeoff could be fatal. Without a
working immune system the body has nothing to fend off deadly bacteria or
The stem cell procedure has an unacceptable mortality rate--between 5 and
10 percent. But the rate in healthier patients has yet to be determined.
"It's in those people we want to reset the equilibrium," Burt said.
And Justin Sears, for one, couldn't agree more.
"The doctors told me not to count on the transplant reversing the
disease," he said. "But I'm really glad I did it. So far, I love it. I
absolutely love it."
Copyright © 2002,
Reversing Paralysis with Stem Cells
September 6, 2001
Image: Courtesy of David Anderson California
Institute of Technology
cells injected into the spinal fluid of newly paralyzed mice and rats can
restore movement, according to a study described yesterday in New Orleans at the
annual meeting of the Society for
Neuroscience. Unlike most stem cell
research, which has focused on repairing damage to small areas of the
central nervous system (such as injuries caused by a stroke), this study is
among the first to demonstrate the efficacy of stem cell treatment in restoring
function over a large region of the central nervous system. Researchers say the
new findings may lead to better treatments for human patients afflicted with
motor neuron diseases such as amyotrophic lateral sclerosis (ALS) and spinal
motor atrophy (SMA), which ultimately lead to paralysis and death.
Investigators led by neurologist Douglas Kerr of Johns
Hopkins University injected neural stem cells (like those shown in the
photograph) into the cerebrospinal fluid of 18 rodents infected with the
Sindbis virus, which normally leads to permanent paralysis. Several weeks later
the cells had migrated from the injection site at the based of the spinal cord
up to the so-called ventral horn, a region that contains the bodies of motor
nerve cells. "After eight weeks we saw definite functional improvement in half
of the mice and rats," Kerr reports. "From 5 to 7 percent of the stem cells that
migrated to the spinal cord appeared to differentiate into nerve cells."
Exactly how so few nerve cells can confer this considerable improvement in
function is a question the team is working to explain. "It could be that fewer
nerve cells are needed for function than we suspect," Kerr surmises. "The other
explanation is that the stem cells themselves havenít restored the
nerve-cell-to-muscle units required for movement but that, instead, they protect
or stimulate the few undamaged nerve cells that still remain." Whatever the
answer, the results do offer hope. "Under the best research circumstances," says
team member Jeffrey
Rothstein, "stem cells could be used in early clinical trials within two
years." --Kate Wong
Harvests Human Stem Cells
JULY 11, 02:19 EST
Va. Lab Harvests Human Stem Cells
Dr. William E. Gibbons
AP/Gary C. Knapp [19K]
NORFOLK, Va. (AP) ó Virginia scientists have become the first
researchers to create human embryos in the lab for the sole purpose
of harvesting their stem cells.
Until now, scientists had derived stem cells only from excess embryos
donated from infertility treatments. In this case, the scientists
approached donors and informed them that their eggs and sperm would
be used to develop embryos for stem-cell research.
The work, conducted by researchers at the Jones Institute for
Reproductive Medicine in Norfolk, drew criticism from religious
conservatives opposed to embryo research.
``I think this is a cautionary tale against starting down the
slope,'' Richard Doerflinger of the National Conference of Catholic
Bishops told The Washington Post in Wednesday's edition.
``It's still killing a human being,'' Mary Petchel, president of the
Tidewater chapter of the Virginia Society for Human Life, told The
Virginian-Pilot of Norfolk, Va.
Scientists who conducted the work said several review panels had
assessed the ethical implications and concluded that the approach was
at least as ethical as using spare frozen embryos.
The group extracted eggs from 12 women, who signed consent documents
and were paid $1,500 to $2,000 each, according to William Gibbons, a
reproductive endocrinologist who was not involved in the work.
Of the 162 eggs collected and inseminated by donor sperm, 50 embryos
were successfully created. The researchers destroyed 40 of those to
get the stem cells that resided inside. The work was done with
The results appear in the July issue of the journal Fertility and
Sterility, published Wednesday. The study began in 1997 and concluded
Interest in embryonic stem cells centers around their ability to
generate other tissues of the body. Doctors hope using stem cells
could possibly cure diseases as Alzheimer's, diabetes, cancer,
Parkinson's, and spinal cord injuries.
President Bush has said he will soon decide whether to allow taxpayer
dollars to be used for research on embryonic stem cells. He is under
pressure from patient groups that favor the research and opponents
who feel the work is inherently unethical.
Transplanted human stem
cells develop into broad range of tissues
8 November 2000
Adult human stem cells taken from bone marrow
have been induced to develop into a wide range of normal tissues, including
bone, cartilage, fat, tendon and muscle, when transplanted into fetal sheep. The
transplanted human cells have persisted in various sheep tissues for over one
year without rejection by the sheepís immune system. The study offers promise
that in the future these cells may be useful for tissue repair or regeneration
and for treatment of degenerative diseases such as muscular dystrophy.
study reported in the November issue of Nature Medicine, researchers harvested
mesenchymal stem cells (MSCs) from adult bone marrow. Although many institutions
are currently investigating various types of stem cells, this is the first study
examining transplantation of human MSCs in the fetal sheep model. In this
current study, human MSCs were transplanted into fetal sheep early in gestation,
at either 65 days or 85 days, before and after the brief window of time when
their immune systems mature and become active.