CHICAGO—A novel cell therapy using retinal pigment epithelial (RPE) cells attached to tiny gelatin microbeads implanted in the brain can relieve the symptoms of patients with moderate to advanced Parkinson’s disease, according to a pilot study reported by Roy A. E. Bakay, MD, and colleagues at the 76th Annual Meeting of the American Association of Neurological Surgeons.
“This is a proof of principle [that this approach with intrastriatal implantation of RPE cells on gelatin microbeads] can be done safely in humans and that it produces sustained improvement in Parkinson’s disease symptoms,” Dr. Bakay told Neurology Reviews. “A phase II study will produce scientific confirmation of positive or negative results by the end of the year.”
Implantation of RPE Cells for Parkinson’s Disease
The pilot study of the investigational treatment, called Spheramine, used human RPE cells. “Hundreds of treatments can be obtained beginning with the cells harvested and prepared from a single pair of eyes,” said Dr. Bakay, the A. Watson Armour III and Sarah Armour Presidential Chair and Residency Research Director in the Neurosurgery Department at Rush University Medical Center in Chicago. RPE cells are found in the inner layer of the retina and normally produce levodopa. The cells used in this study were cadaveric—obtained from an eye bank.
MRI-guided stereotactic surgery was used to implant the microbeads in the more affected side of the brain in six patients with moderate to advanced Parkinson’s disease. The microbeads were injected through five needle tracts for even distribution of cells in the posterior putamen, and the procedure required one to three days of hospitalization. The main outcome measure was the motor score of the Unified Parkinson’s Disease Rating Scale (UPDRS) after the patient had been off antiparkinsonian medication for at least 12 hours.
Dr. Bakay reported that at 48 months following treatment, UPDRS motor scores had improved by an average of 44% from baseline, and patient-reported quality-of-life scores had improved 23% from baseline. Long-term improvement or stabilization of symptoms was maintained for a minimum of two years after implantation. At this time, several patients have been followed for six years; the study has been extended to 10 years of follow-up.
The most frequent adverse event was postsurgical headache, which resolved spontaneously within one to two weeks. There were no treatment-related adverse events.
The researchers were somewhat surprised by how well the patients did during the 48-month follow-up period. “Only one patient has recently gone on to get deep brain stimulation after five years,” Dr. Bakay said. “The results of this study are very encouraging. Spheramine is well tolerated through several years of follow-up, and improvement in parkinsonian symptoms is sustained.”
Phase II Study Under Way
Dr. Bakay noted that work is being continued in a multicenter, double-blind, randomized, sham surgery–controlled phase II study. The main change from the pilot study is that the treatment group will have microbeads implanted in both sides of the brain. The sham surgery–controlled group will have skin incisions and burr holes through the skull but with no penetration of the dura mater. To date, 71 patients have been randomized, and efficacy results are expected later in 2008.
Although Spheramine durability in humans is still under investigation, RPE cells survive for more than a year in monkeys, and autopsy data have shown RPE cell survival of 18 months in humans, said Dr. Bakay. “This is a new and promising therapy that may provide consistent levodopa to patients that will smooth out the ordeal of immobility in the ‘off’ phase and the disability of dyskinesia in the ‘on’ phase,” he concluded.
—Janis Kelly