An innovative therapeutic strategy of the implantation of Spheramine, consisting of retinal pigment epithelial (RPE) cells attached to gelatin based microcarriers, into the brain, could improve the symptoms in moderate-to-severe Parkinson disease (PD), according to a research study presented at the recent annual meeting of the American Association of Neurological Surgeons held at Chicago.
Dr Roy A. E. Bakay, a neurosurgeon at the Rush University Medical Center, Chicago, investigated 6 moderate-to-advanced PD patients for the efficacy, safety and tolerability of Spheramine, implanted in the more affected side of the brain. Disease stage, severity of PD symptoms and levodopa responsiveness were the parameters considered for patient selection. Following a 4-year evaluation (6-10 years in some patients), researchers found an improvement in symptoms with no serious side effects related to Spheramine, other than postsurgical headache, which resolved spontaneously within 1-2 weeks. Motor scores of the Unified Parkinson Disease Rating Scale (UPDRS) were used to assess the efficacy of Spheramine implantation on patients who had not taken their antiparkinsonian medication for at least 12 hours. Quality of life was measured after evaluating the responses of the patients using PDQ-39 score (Parkinson Disease Questionnaire contains 8 dimensions including mobility, activities of daily living, stigma, social support, emotional well-being, communication, cognition and bodily discomfort). The researchers found a 44% and 23% improvement from baseline, in UPDRS scores and in the quality of life (of the affected patients), respectively, at 48 months.
The RPE cells (found usually in the back of the eye) are cultured under standardized conditions, and attached to microscopic beads before implantation, as it helps the cells to survive in the brain. The RPE cells in Spheramine help in producing levodopa, which is the precursor of dopamine, a neurotransmitter in the brain. It has been found that as the disease advances, the level of dopamine decreases progressively resulting in an increase in the severity of symptoms. The cells on implantation have the potential to increase the dopamine production, thereby offering hope for patients suffering from PD. Based on the positive findings of the pilot study, the scientists have initiated a Phase IIb, double-blind, multicenter, randomized, sham surgery-controlled study (STEPS) to further assess the efficacy of Spheramine.
A previous study by Flores, et al. (Journal of Neuropathology and Experimental Neurology, 2007) investigates the long-term survival of the implanted human retinal pigment epithelial cells attached to gelatin microcarriers (hRPE-GM), in 22 Sprague-Dawley rats, with the help of RPE-specific markers (characterized in vitro). The study suggested that hRPE-GM implants could survive even without immunosuppresion, and have the potential to be used as an alternative method to treat PD.
Parkinson disease, a neurodegenerative disease, affects more than 4 million people worldwide. It usually occurs in people above 50 years of age (with a male predilection) and around 50,000 new cases are reported every year in the United States. Currently, there is no known cure for PD and medications like levodopa, anticholinergics, dopamine agonists and monoamine oxidase-B inhibitors provide inadequate relief from symptoms, especially in the advanced stages of the disease. Several new methods are being evaluated for treating PD such as gene therapy, neuroprotective treatments and neural transplantation.
As socioeconomic burden due to Parkinson disease is extensive, the novel approach of implanting Spheramine in the brain could reduce the impact of the disease, both on the economy as well as on the affected individuals.
Reference
1. Cell-Based Therapy Shows Promise in Patients with Parkinson’s Disease. News Release. Rush University Medical Center. Last accessed April 30, 2008.
2. Flores J, Cepeda IL, Cornfeldt ML, O’Kusky JR, Doudet DJ. Characterization and survival of long-term implants of human retinal pigment epithelial cells attached to gelatin microcarriers in a model of Parkinson disease. J Neuropathol Exp Neurol. 2007 Jul;66(7):585-96.
