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Thursday, May 01, 2003

By Anita Srikameswaran, Post-Gazette Staff Writer

Investigators are beginning to think that brain cell transplants might work as therapy for stroke patients, citing new findings of improved arm movement and memory in the second group of stroke survivors to undergo the novel procedure.

Dr. Douglas Kondziolka, a neurosurgeon at the University of Pittsburgh Medical Center, yesterday presented findings from the latest clinical trial of neuron transplantation at the American Association of Neurological Surgeons annual meeting in San Diego.

Study participants tell Kondziolka that the procedure was of great benefit. Those whose memories became better say that it "absolutely improved their lives in a huge way," he said.

"It's taken people who were dependent on their spouses and made them more independent," Kondziolka said. "That's a huge thing."

Kondziolka performed the world's first neuron transplant in a stroke patient in June 1998. The first trial showed the procedure was safe and some of the 12 participants said their symptoms had improved.

Eighteen patients participated in the new trial, which was conducted at UPMC and Stanford University. All patients were between 40 and 70 years old and had suffered a stroke in the basal ganglia region in the brain an average 3 1/2 years before the transplant procedure.

Seven people received 5 million human neurons, or brain cells, that were developed in a California lab, Layton Bioscience Inc. Seven others were each given 10 million cells. Four people did not get cells but were monitored for comparison. All participated in a two-month rehabilitation program.

The researchers hoped that the new cells would be incorporated into the brain and take the place of cells that were killed by the strokes.

The treated patients improved from their baseline measurements and had better scores than the untreated group on a measure of arm movement, which includes pinching, gripping, grasping and gross hand movement, and on another measure of wrist and hand motion.

People who received neurons fared better on memory tests. Gains were seen in a group of nine patients who had neuropsychological testing of their ability to do things such as initiate, plan and think abstractly. Prior to the cell implantation, one participant couldn't set up appointments or copy a drawing, Kondziolka said. Now she is able to run her own life.

Sue Hamilton, 54, of Adams, N.Y., didn't undergo such a dramatic change, but she said being part of the research and getting a neuron transplant was "a wonderful experience." She got 10 million cells on Jan. 29, 2002.

"My feeling from the very beginning was that if nothing happened for me, at least it might help someone else later on," Hamilton said. "With a research program, you don't expect instant results."

A few days before Christmas 1996, the fifth-grade teacher felt her legs give way during a faculty party. Hamilton guessed that she was feeling the effect of three alcoholic drinks, so her husband took her home and tucked her into bed. He called an ambulance when he couldn't rouse her the next morning.

Hamilton awoke on Christmas Day to the news that she'd had a stroke. She had speech problems and was paralyzed on the right side. She got around in a wheelchair for several months, but eventually learned to talk again and to walk with a cane.

She can now raise her still weakened right arm to her shoulder, but can't pick up objects or manage buttons, so she has difficulties dressing herself.

After hearing about the neuron transplant research on a television program, Hamilton called UPMC to learn more. Eager to volunteer, she maintained contact with the program for more than two years. She had almost given up when the researchers called to offer a spot.

"There was always the chance that I might be a control (an untreated patient)," Hamilton said. "That was really worrying me. But I thought, it's got to be done."

Her husband was first to notice a change. He used to push her right leg away in bed because it was too cool. But about a month after the transplant, he pointed out that her leg had become warmer.

"That's probably the biggest thing that's changed for me," Hamilton said. "This is the cells, probably. What else could it be?"

She can also sense light touch on her right limbs better than before.

According to Kondziolka, some participants of the first transplant study said that their affected legs felt as if they belonged to someone else and that the transplant seemed to make their limbs feel alive again.

"I don't know what to make of that," he said. "Some of these patients describe a little bit of this, a little bit of that."

The procedure appears to be safe. After the surgery, one patient had a seizure and another had a fainting spell. A participant who was taking a blood thinning drug developed a hematoma between the membranes lining the brain. The complications disappeared after treatment with no damage done.

Kondziolka said that it's not yet known whether the lab-made cells are necessary for success or if the same effect could be achieved by simply administering nerve growth factors, a substance secreted by the transplanted cells.

He is planning the next step of the research, which would test cell implantation in two groups of eight people with more recent strokes -- basal ganglia strokes that are three to 12 months old.