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Senior Citizen Health & Medicine
Human Stem Cell Treatment Restores Motor Function in
Paralyzed Rats
Scientist hopes to move to human clinical trials
next year
May 31, 2007 – The possibility of a restoring motor
function for people suffering paralysis may be more than just a dream.
Researchers grafted human spinal stem cells into rats paralyzed by loss
of blood flow to the spine and they returned to near normal function in
six weeks. The lead scientist hopes to move to human clinical trials
next year.
“We demonstrated that when damage has occurred due
to a loss of blood flow to the spine’s neural cells, by grafting human
neural stem cells directly into the spinal cord we can achieve a
progressive recovery of motor function,” said Martin Marsala, M.D., UC
San Diego professor of anesthesiology and leader of the study.
“This could some day prove to be an effective
treatment for patients suffering from the same kind of ischemia-induced
paralysis.”
Marsala is currently testing the human stem cell
therapy for safety and efficacy in other animal models, and hopes to
move to clinical trials in humans by next year.
The research from the University of California, San
Diego (UCSD) School of Medicine is published in the June 29, 2007 issue
of the journal Neuroscience, which is now online.
Paraplegia from spinal cord ischemia is a serious
complication that occurs in 20 to 40 percent of patients undergoing a
surgical process called aortic cross-clamping. When the surgeon works on
the aorta, a major blood vessel, to correct a potentially lethal
aneurysm, blood flow from the heart must be temporarily blocked with a
clamp.
After 30 minutes, this lack of blood flow can
result in the death of specialized spinal cord neurons called spinal
inhibitory neurons, leading to irreversible spasticity and rigidity, or
loss of muscle control, in the lower limbs, even though the spinal cord
is intact.
“The important difference between spinal cord
ischemia and spinal cord trauma, such as might occur in a diving or car
accident, is that in the ischemia model, no mechanical damage has
occurred to the spinal cord,” said Marsala.
“The spinal cord and brain motor centers are still
partially connected, but there has been a selective loss of inhibitory
neurons in the spinal cord. Since these cells are necessary for
coordinated motor activity, our research aims to replace these lost
neurons by grafting new spinal stem cells, which repopulates the pool of
degenerated neurons.”
For this study, nine of 16 rats with induced spinal
cord ischemia were injected with human spinal stem cells 21 days after
paralysis. The other seven were injected with medium that contained no
stem cells. The recovery of motor function was evaluated in seven-day
intervals, showing a progressive recovery of ambulatory functions in the
rats that received stem cells.
Three of the nine rats injected with hSSCs returned
to walking at six weeks, and three others had improved mobility in all
lower extremity joints. All nine animals grafted with hSSCs achieved
significantly better motor scores than those in the control group, and
showed a consistent presence of transplanted cells in the spinal area.
In all the rats grafted with the stem cells, the
majority of transplanted human spinal stem cells survived and became
mature neurons, according to Marsala. A second study was conducted over
a three-month period, with similar results.
“Other human stem cell transplants in the spinal
cord have focused on repairing the myelin-forming cells,” said co-author
Karl Johe, a researcher at Neuralstem, the company that manufactures the
hSSCs used in the study. “In this study, we succeeded at reconstructing
the neural circuitry, which had not been done before.”
The researchers believe that the therapy may
eventually be proven even more effective in human patients, who would be
able to receive physical therapy once treated.
“Physical therapy may accelerate integration of the
grafted stem cells and enhance their therapeutic benefit,” Johe said,
adding that the goal is to provide a significant gain in functional
mobility of the patient’s legs.
This study builds on Marsala’s previous work in rat
models using human neuronal stem cells, published in October 2004 in the
European Journal of Neurosciences. In that study, significantly improved
motor function, measured by a suppression of spastic movements and
improved muscle tone, was shown in 40 to 50 percent of the animals
tested.
A post-mortem study of those animals showed a
robust maturation of neurons and an increase in the expression of
inhibitory neurotransmitters in the spinal cords of rats that received
transplanted neuronal cells.
Current treatment for debilitating muscle
spasticity is continuous systemic or spinal drug treatments using
implanted pumps. These approaches, while effective to a degree, are
often accompanied by side effects and eventual drug tolerance that
lessens their efficacy.
“These research findings could offer great hope to
people with spinal ischemic injury who suffer from resulting spasticity
and rigidity,” said Marsala.
Editor’s Notes:
Additional contributors to the paper include Dasa
Cizkova, Osamu Kakinohana, Karolina Kucharova, Silvia Marsala, Karl Johe,
Thomas Hazel and Michael P. Hefferan.
The study was supported in part by grants from
the NIH. This research was supported by grant NS 40386 (M.M.),
Neuralstem Inc., MD and Centrum of Excellence APVV 51-002105 grant
(D.C.).
The California Institute for Regenerative
Medicine (CIRM) recently awarded Marsala a $2.4 million grant for his
research utilizing stem cells to repair spinal cord injury resulting
from transient ischemia. He is also collaborating with the University of
Michigan on a new $5 million stem cell research project, with Marsala
focusing on the potential use of stem cells to treat the paralyzing
disease amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease.
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