Cell Transplantation Found To Be Safe and Feasible in Stroke Patients, According to Pittsburgh Researchers
PITTSBURGH, August 21, 2000 — Cell transplantation was found to be safe and feasible in stroke patients, according to University of Pittsburgh researchers in a study published in the journal Neurology. They also reported that half of the patients who underwent neuronal transplantation following stroke showed improvement in motor function. PET scan results also suggest cell viability as evidenced by increased metabolic activity in the area of the stroke was seen in six patients.
The phase I study evaluated the safety and clinical effects of an experimental treatment aimed at reversing neurological deficits from stroke through implantation of human neuronal cells in 12 stroke patients.
Principal investigators in the study were Douglas Kondziolka, M.D., professor of neurological surgery and radiation oncology at the University of Pittsburgh department of neurological surgery , and Lawrence Wechsler, M.D., professor of neurology and neurosurgery at the University of Pittsburgh School of Medicine and director of the University of Pittsburgh Medical Center Stroke Institute.
The nine men and three women in the study varied in age from 44 to 74 years. In eight patients, the stroke involved only the basal ganglia region of the brain and in four patients, both the basal ganglia and regional cortex were involved. All patients had stable neurologic deficits at least two months prior to implantation.
The first four patients were treated with two million neurons implanted at three sites along a single needle pass within the basal ganglia. The remaining eight patients were randomized to receive either two million neurons along one needle pass or a total of six million neurons implanted along three trajectories.
Assessment of safety and feasibility was performed using the NIH Stroke Scale (NIHSS), European Stroke Scale (ESS), Short Form 36 (SF36) and Barthel Index (BI).
"All outcomes measurements were consistent in identifying a trend toward improved scores in the group of patients who received six million neuronal cells," Dr. Kondziolka reported.
At the 24-week follow-up evaluation, six of the 12 patients had improved scores on the ESS, three patients were unchanged and three patients deteriorated compared to their baseline scores prior to neuron implantation. Motor elements of the ESS accounted for much of the change noted in patients, the study reported. NIHSS scores reflected similar changes in functional performance. At the 24-week point, eight patients had improved scores, one patient was unchanged and three deteriorated compared with their baseline scores.
"These indications of efficacy must be tempered by the fact that signs of improvement were not consistent," Dr. Wechsler said. "Some patients had worse stroke scale and stroke disability scores at the end of six months than they had at the time of implantation."
An equal number of patients had no improvement or worsening in stroke or disability scales as had improvement. In several patients, inter-current events (including a new-onset seizure disorder, a new stroke and worsening renal failure) adversely affected their functions and quality of life, so that some signs of improvement could have been obscured, according to the study.
"In future studies, we plan to use additional instruments that will evaluate persistent neurologic deficits and their impact on function," Dr. Kondziolka said.
LBS-Neurons originated from a human teratocarcinoma, a tumor of the reproductive organs that is composed of embryonic-like cells, which was removed from a 22-year-old cancer patient in the early 1980s. Layton BioScience, Inc. has licensed a patented process that uses several chemicals to transform this cell line into fully differentiated non-dividing human neuronal cells (LBS-Neurons) that can be used in clinical applications. In extensive pre-clinical testing, implants of LBS-Neurons reversed cognitive and motor deficits in animals in which stroke had been induced.
The procedure begins with the placement of a stereotactic frame on the head of the patient. The frame is a standard tool in neurosurgery to provide a fixed way to find specific locations within the brain. The patient then receives a CT or MRI scan of the brain and the surgical team makes its final decision for location of cell implantation.
Concurrently, the University of Pittsburgh Immunologic Monitoring and Diagnostic Laboratory team thaws the human neuronal cells that were frozen by and transported from Layton BioScience, Inc.
After the cells are transferred to a long-needled syringe, the surgeon uses CT to guide their injection at multiple sites. The surgeon injects these cells through a small opening in the skull, and patients leave the hospital the next day.