Within two weeks, treated animals were about20 percent less likely to favor the unaffected side of their bodies andexperienced about a 25 percent improvement in balance, compared tountreated controls, Medical College of Georgia researchers say.
Their findings are being presented during the 34th annual meeting of the Child Neurology Society Sept. 28-Oct. 1 in Los Angeles.
“Wefound that when these cells, provided by Athersys, Inc., were injecteddirectly into the brain, it significantly improves the outcome in theanimals,” says Dr. James E. Carroll, chief of the MCG Section ofPediatric Neurology and the study’s principal investigator.
Athersys,Inc., a Cleveland-based biopharmaceutical company pursuing cell therapyprograms in cardiovascular disease, stroke, cancer and other diseases,funded the research in which about 200,000 cells were injected directlyinto the brain injury site.
The adult stem cells, calledmultipotent progenitor cells because of their ability to make differenttypes of tissue, were taken from the bone marrow of rats and expandedby Athersys for dosing in the injury model, Dr. Carroll says.
Sevendays after injury, stem cells were injected directly into the brains of22 animal models through a tiny hole in the skull. As with humantransplant recipients, the animals were placed on immunosuppressivetherapy to avoid rejection, although Athersys’ experience in multipleanimal models for human disease has shown donor-recipient matches andimmunosuppression are not required.
Behavioral tests seven daysafter transplant showed a trend toward recovery and significantrecovery by day 14. About 1 percent to 2 percent of the transplantedcells actually survived, apparently replacing some cells destroyed bythe original injury, while others helped injured cells recover.
“Recoverymight be even more important in baby brains than forming new cells,”Dr. Cesario V. Borlongan, neuroscientist at MCG and the VeteransAffairs Medical Center in Augusta, says of newborn brains that recovermore readily than adult brains. Dr. Borlongan, a co-author on theabstract, is exploring stem cell therapy’s potential for aiding strokerecovery, including the use of clinical-grade human adult cellsprovided by Athersys in a stroke animal model. About 80 percent ofstrokes are caused by clots that cause ischemic brain injury similar tothat of cerebral palsy.
The MCG researchers have evidence thatthe healing benefit of stem cells comes from nourishing factors theysecrete. The cells seem attracted by chemokines, growth factors thatrally to an injury site, Dr. Carroll says. Next steps include lookingat longer-term recovery and at whether surviving stem cells actuallyfunction as brain cells, networking with other cells by forming pointsof communication called synapses.
Perhaps most importantly, theyalso will look at whether stem cells produce similar results when theyare given intravenously rather than injected directly into the injurysite, Dr. Carroll says. “If the ideal way of doing it scientificallydoesn’t work, why move on from here?” he says. “Now that we know itdoes work, we are going to look at different methods of injection totry and find the one that is the easiest. We think the chemokines, atleast in part, attract the cells, so we hope it will work even whengiven through the bloodstream.”
He notes that the therapy likelywill need to be done soon after injury. Whether this therapy could helpthe some 500,000 people in the United States living with cerebral palsystill must be explored, he says.
He and Dr. Borlongan note muchwork needs doing before their findings might move to clinical trials.But they are optimistic that the availability of clinical-grade cellswould expedite such a move.
“We hope this will eventually besomething that can be used in the neonatal intensive care unit inbabies with severe asphyxial brain injuries,” Dr. Carroll says ofcerebral palsy patients. He and other pediatric neurologists andneonatologists already have begun to discuss such possibilities.
“Theseresults suggest another promising avenue for stem cell therapy, thistime to help newborn babies recover from a potentially devastatinginjury of birth for which there currently is no treatment,” says Dr.Gil Van Bokkelen, chairman and chief executive officer of Athersys.
Ischemicbrain injury accounts for about 10 percent of cerebral palsy, broadlydefined as brain injury that occurs before or during birth, and about80 percent of strokes. For every 1,000 babies born, one or two havecerebral palsy, with consequences ranging from undetectable to majorphysical and mental impairment. Currently there is no treatment torepair or reduce the damage of cerebral palsy; tPA was approved in 1996by the U.S. Food and Drug Administration as the first stroke treatmentto reduce the damage of ischemic injuries.
Co-authors on thestudy include Dr. David Hess, chair of the MCG Department of Neurology;Dr. Lin Xu, research scientist; Drs. Noriyuki Matsaukawa, Guolong Yu,Takao Yasuhara and Koichi Hara, postdoctoral fellows; and Athersysscientists Robert Mays, Jim Kovach and Robert Deans.
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