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Stanford Report, June 5, 2002

Modified cancer cells may treat stroke

By SEAN GRIFFING

In 1996, a 53-year-old man suffered a major stroke. After a year of recovery, he still experienced weakness on his right side and difficulty walking. There are no cures, no ways to bring back abilities lost when a small portion of the brain dies from lack of oxygen.

But this particular stroke victim beat the odds within the past year. His gait has improved; his right arm works better; and he can grab objects with his right hand. While the official results aren't in, his improvement may have come from an experimental surgery as part of a four-year study at Stanford University Medical Center and the University of Pittsburgh.

Gary K. Steinberg, MD, PhD, a neurosurgery professor and co-director of the study, placed 5 million former tumor cells in 25 spots around the site of the patient's stroke. Before he implanted the cells, they were transformed into immature nerve cells incapable of dividing. But once inside the brain, they learn to mimic cells around them, behaving more like mature nerve cells.

"We haven't proved by any means that this is an effective therapy in terms of improving neurological function after a stroke -- that's why we're doing the trials," said Steinberg. "We're not claiming that this therapy is going to cure patients of their stroke. If we see a modest, but clinically significant, benefit we'd be overjoyed."

Researchers are also establishing the safety of the treatment. Years of research and one previous human trial indicate they're on track. Though the cells originated from one man's testicular cancer, they've never caused cancer in 20 years of study. Steinberg believes the procedure is safe, feasible and does not lead to significant adverse effects. His team will get its first real results in about six months.

For the study, the patients were split into two groups, those who received 5 million cells and those who received 10 million. In each group of nine patients, two were not operated on. To keep the evaluating neurologists and physical therapists from guessing if the patients received treatment, all the patients wore hats, Steinberg noted.

The surgery itself has a remarkably quick turnaround. Patients are awake but sedated as a small portion of their brain -- about the size of a pencil tip -- gives passage to a metal needle that plunges deep inside. The doctors plot their approach prior to surgery using magnetic resonance imaging and computer calculations. All that remains during surgery is to deposit the cells in 25 different locations surrounding the stroke site. After surgery, a small titanium plug is placed in the patient's skull to seal the hole. The patient can go home the next day.

In the first year after treatment, all patients have to come in for 16 visits. They also go through eight weeks of constraint therapy (where their working arm is restrained in order to encourage the brain to relearn how to use the other).

Scientists are still debating how the former tumor cells work. Neurons have been likened to the brain's wiring. When a stroke occurs, it's as if some wires have been cut. "Initially, the idea with these transplants was that you would be implanting cells that would grow new circuits to repair tissues," Steinberg said.

But the improvements shown were so rapid in animal studies that the theory didn't hold up. "They may act like little growth substance factories that improve the environment and facilitate natural mechanisms of recovery," he explained. Instead of acting as connectors, the new cells may somehow signal surviving nerve cells to function better.

In the future, Steinberg and his colleagues hope to place even more cells around the site of the patient's stroke. But before that's done, there will have to be additional testing. If the current study turns out well, it may lead to an even larger one. Steinberg plans to try this therapy on patients with traumatic brain injury, spinal cord damage, Parkinson's disease, Alzheimer's disease, epilepsy and brain tumors.

"We are on the verge of a truly revolutionary change in the way we treat neurological disease," he said. "With the developments that have occurred in molecular biology, stem cell biology and computer technology, we think the possibility of being able to restore function in patients with debilitating neurological disease is on the horizon."



Doctors transplant nerve cells into brain of stroke-impaired patient (5/9/01)

Brain cooling shows promise as technique to prevent long-term stroke damage (1/10/01)

$4.7 million grant sparks stroke research collaboration (11/17/99)