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Transplanted neurons showing signs of life in stroke patients
Thursday, April 29, 1999 By Anita Srikameswaran, Post-Gazette Staff Writer
Color them excited.
The scientists who put human brain cells into stroke patients have seen brain scans turn from black to orange, suggesting that the transplanted cells are working and sustaining hopes that the cells might repair stroke damage.
Yesterday at a meeting of the American Association of Neurological Surgeons in New Orleans, Dr. Douglas Kondziolka of the University of Pittsburgh Medical Center presented findings of increased brain metabolism at the sites of neuron transplant in three out of four stroke patients.
"We can't be sure, but we think it's evidence of the neurons successfully grafting to the host brain," said Kondziolka, principal investigator of the clinical study that began last summer.
Four patients have had a PET, or positron emission tomography, scan six months after the transplant procedure. By September, all 12 study participants will have had a six-month scan. The investigators plan to scan them again a year after they had surgery.
Eight patients have told investigators that they have experienced improvements in sensation and strength, and several said their memory was better. According to Kondziolka, one man whose arm felt dead after the stroke now feels there is some life in it.
"We don't know what to expect when looking at benefit," the neurosurgeon said. Scans cannot say what areas of the stroke affect strength, sensation or memory, so people may note very different results.
For the scientists, the measurable changes in metabolic activity provide better grounds to consider this first human experiment a success.
A PET scan indicates the activity of the tissue under examination. For the brain scans, glucose use was measured. In a stroke region, the neurons are dead and don't take up glucose for energy, so the area looks black on a scan.
"Yellow is on fire, meaning high metabolism," Kondziolka explained. "Reddish is kind of normal. Now the areas are looking kind of orangy."
There was a lot of discussion among the researchers about what the metabolic changes mean. The neurons are consuming energy, but are they behaving normally? That question has yet to be answered.
"In two of the patients, there's almost like a global benefit through that hemisphere, away from where the cells were put," Kondziolka said. "This was something we found very fascinating."
It could mean that the transplanted neurons are sending out chemical signals and reconnecting distant links that had been lost at the time of the stroke, said Dr. Carolyn Meltzer, medical director of UPMC's PET Facility. Stroke patients may have reduced metabolic activity distant from the affected region. In some transplant recipients, glucose use in the brain appears to be normalizing.
"Of course, we have to couch this in terms of a preliminary finding," she cautioned. "We don't know what they'll look like six months later."
Magnetic resonance imaging, or MRI, of the patients' brains did not show any signs of inflammation or new masses, which could also have explained the increased activity, the doctors said.
One of the patients studied did not show any change on the PET scan, but still experienced a small subjective improvement in symptoms. It may be that the cells did not actually "take" or that the scan could not pick up the difference in metabolism.
This first phase of testing is designed to uncover any dangers of the treatment. One person had a seizure, a complication of the original stroke. There have been no other ill effects. In the procedure, a small hole is drilled into the skull and about 2 million neurons are injected in and around the stroke region.
The researchers, who still get 30 to 50 letters a week from people eager to volunteer for the experiments, are putting together a proposal to take to the Food and Drug Administration for a second phase study, in which more neurons will be transplanted to see if dose has an impact on recovery.
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