Stanford Report, May 9, 2001
|Doctors transplant nerve
cells into brain of stroke-impaired patient
BY KRISTA CONGER
Last week, human cells that were coaxed in the laboratory to become neurons were implanted into the brain of a stroke-impaired man in his 50s at Stanford University Medical Center. The surgery on May 1 was the first in a nationwide, phase-II clinical trial being co-directed by Stanford neurosurgeon Gary Steinberg, MD, PhD.
"The procedure went extremely well and the patient is doing fine," said Steinberg, noting that the patient left the hospital May 3. Steinberg, professor and chair of neurosurgery, will monitor the man for the next four years to assess the effect of the implanted neurons. Neurosurgeons and neurologists hope the new neurons will be able to pinch-hit for their stroke-damaged counterparts and relieve the long-term weakness and loss of motor control suffered by many stroke victims. Currently there is no effective treatment for reversing these symptoms.
"This trial marks the first time neurons have been transplanted into the brains of stroke patients," said Steinberg. "If transplantation with cultured neurons can improve the symptoms of chronic stroke, it will have enormous implications for stroke patients worldwide."
According to the National Institute of Neurological Disorders and Stroke, 4 million Americans are living with the effects of a past stroke and more than 700,000 Americans suffer a stroke each year. One-third of new stroke victims die, and about 20 to 30 percent are permanently disabled. Stroke is the leading cause of disability in the United States.
The implanted cells are synthesized from human tumor cells by Layton BioScience Inc. of Sunnyvale, Calif. The company uses a patented process to transform the tumor cells into non-tumorigenic, non-dividing human neuronal cells. The cells, called LBS-Neurons, are purified for use in transplantation studies. Although the cells are derived from a human tumor, they have never developed into tumors during years of research using animals, Steinberg said.
Preliminary results of a phase-I trial of the neurotransplantation procedure conducted at the University of Pittsburgh on 12 patients indicated the cells were safe for use in humans. The results also hinted that the new neurons may be able to correct at least some of the permanent neurological symptoms that linger after a stroke.
"The results of that study demonstrated first and foremost that the procedure is feasible and safe; there were no significant adverse effects," Steinberg said. "Although the study was not designed to prove efficacy because the number of patients was too small, there was a suggestion that half the patients experienced improved motor function six months after implantation."
Now scientists at Stanford, the University of Pittsburgh and the University of South Florida are recruiting additional patients for a larger study to determine if the implanted neurons can actually benefit chronic stroke patients.
A total of seven patients are needed to participate in the first round of the trial at Stanford, to be followed by seven more if the results are promising. The first group of seven will be treated with 5 million of the manufactured neurons, and the second group of seven will receive 10 million cells.
To qualify for the study, patients must have suffered a stroke in the basal ganglia region of the brain one to six years ago and must have permanent major weakness or partial paralysis on one side of the body. They must be between the ages of 18 and 75 and be able to participate in eight weeks of physical therapy at Stanford following the implantation procedure.
Prospective study patients are given two consecutive, rigorous physical and neurological exams about one month apart to assess their eligibility and confirm that their symptoms are not changing over time. Those chosen to participate will be randomly assigned into either a treatment or a control group. In each group of seven participants, five will receive the implanted neurons and two will not.
During the surgery, the manufactured neurons are implanted in 25 separate areas around the stroke-damaged area of the basal ganglia. Steinberg uses an MRI scan to pinpoint the precise location of transplantation, and a frame attached to the patient's skull guides the injection of the neurons through an opening in the skull about the size of a pencil eraser. Patients are sedated but awake during the implantation, and usually can be discharged from the hospital within 24 to 48 hours.
All participants will undergo eight weeks of physical therapy at Stanford. Those in the treatment group will begin their therapy after the implantation procedure. The therapy, known as "constraint" therapy, will involve immobilizing the functioning arm to force the brain to re-learn how to move the affected limb. Physicians will assess the participants' degree of motor control and extent of weakness in the affected half of the body at regular intervals in the first year following implantation and then annually for the next four years.
Other Stanford physicians participating include David Tong, MD, assistant professor of neurology and neurological sciences; Jeffrey Teraoka, MD, assistant professor of functional restoration; Robert Negrin, MD, associate professor of medicine; Michael Marks, MD, associate professor of radiology; and Richard Jaffe, MD, PhD, professor of anesthesiology.
Layton BioScience, Inc. is
sponsoring the study. To volunteer for the trial, call Teresa
Bell-Stephens at (650) 723-5575 or email her at email@example.com.