Trials Here First to Use Stem Cells for Brain Injuries / Doctors Try to Devise a Therapy That Would Assist Child Patients

By Todd Ackerman
Houston Chronicle
December 23, 2005

Houston doctors soon will begin treating brain-damaged children with their own stem cells in an attempt to develop the first-ever therapy to repair injured brains.

Pediatric surgeons at the University of Texas Medical School at Houston and Memorial Hermann Children's Hospital said this week they have received Food and Drug Administration approval to test the new treatment, which is based on therapeutic abilities of adult stem cells considered unthinkable a decade ago.

"This would be an absolutely novel treatment," said Dr. James Baumgartner, who, along with Dr. Charles Cox, is one of the trial's principal investigators. "Given what a big problem brain trauma is in society, any new therapy could make an important difference."

The trial, the first to use any kind of stem cells in brain trauma, will enroll 10 patients between the ages of 5 and 14 within 48 hours of a head injury. It will be a Phase One trial, meaning its main emphasis will be to make sure the procedure is safe.

Existing treatment for brain injuries is limited. Although brain injury victims can regain some function through rehabilitation, the brain does not repair itself effectively like bone, muscle and other organs.

Drugs and surgery can reduce swelling that leads to secondary injuries but do nothing for the primary damage.

Surprising properties

As a result, brain trauma is the No. 1 cause of death and disability among people 25 and under. Roughly 80,000 U.S. adolescents suffer severe head injuries each year, up to a quarter of them fatal. Survivors of even moderate injuries often are debilitated for life.

Additionally, the trial could further demonstrate the potential of adult stem cells, whose use is hailed by many as more ethical than destroying embryos to harvest their stem cells. Although scientists say embryonic stem cells are more versatile, they have been surprised at the properties uncovered in adult stem cells in recent years.

One of the most impressive showings was demonstrated by cardiologists at the Texas Heart Institute and St. Luke's Episcopal Hospital. In a study in Brazil, they showed that stem cells taken from patients' bone marrow and injected directly into the heart not only improved blood flow and blood vessel formation, but grew new tissue as well. In early 2004, the doctors began a similar study in the Texas Medical Center.

But it was other research that prompted Baumgartner and Cox to consider the stem cell trial for brain injuries.

Previous studies had indicated that bone marrow can migrate to an injured area of the brain, differentiate into new neurons that support cells, and induce brain repair. In the earlier research, brain-damaged rats' motor functions and memories improved dramatically after they were injected with stem cells.

In the trial, bone marrow will be extracted from the patient's hip and processed to derive two types of progenitor stem cells: those that differentiate into bone, cartilage, fat cells and neurons; and those that form the cells needed for blood.

Baylor College of Medicine's Center for Cell and Gene Therapy will process the bone marrow and return it to Memorial Hermann Children's, where it will be given to patients intravenously. Because researchers expect the stem cells to migrate to the brain, the cells will be injected into the patients' arms.

The study is expected to start in late January or early February. Baumgartner said the bulk of patients should come as the weather warms up and injuries occur more frequently.

Under the FDA's protocol, the researchers must enroll patients one at a time, each new enrollment coming only after the treatment has been shown to be safe over a two-week period with the previous patient.

The patients will be reviewed at one month and six months after being discharged.

The proposal was under review for a year before the FDA and the UT-Houston's institutional review board for research projects approved it.

Baumgartner and Cox said they have heard some criticism about starting research on the untested therapy with children. But noting the dimension of the problem among young people, the therapy's potential with adolescents and the differing responses likely in adults, they said denying it to children "would be a disservice."

Federal regulations provide special protections for children in clinical trials, requiring institutional review boards to hold researchers to a higher standard when evaluating the risks and benefits.

Dr. Stacey Berg, a Baylor pediatric hematologist/oncologist and associate dean for research assurances, said an important consideration is a child's inability to give informed consent. That role is ceded to parents.

Potential impact

Cox said the trial could lead to a whole new paradigm in brain trauma treatment and prognosis. Even marginal improvement could mean a great deal, he said.

"This could have a huge impact on families and society," Cox said. "It could be the difference between being able to recognize your loved ones and not being able to, or between doing things for yourself or having to rely on others."

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