ABSTRACT:

Parkinson disease is a neurodegenerative disorder. This syndrome is mainly a progressive dopaminergic cell loss in the substantia nigra pars compacta and a degeneration of the nigrostriatal dopaminergic pathway. Currently pharmacological therapy focused primarily on ameliorating the dopamine deficiency in the brain. Mostly requiring levodopa therapy for controlling symptoms 3 to 5 years after the diagnosis; but this therapy can lead to motor fluctuations and dyskinesias. To overt these symptoms studies have shown that continuous striatal delivery of levodopa or dopamine may be closer to a physiologic state and have a better therapeutic profile than oral levodopa.

This continuous striatal delivery is an experimental approach and the basis of this study. It is found that human retinal pigment epithelial (RPE) cells produce levodopa. These can be isolated and passively attached to gelatin microcarriers. These in return are transplanted into the brain and attain prolonged survival even in absence of immunosuppressive therapy. These preclinal studies suggest safety and effectiveness of delivering a durable source of levodopa for the implantation into the striatum of patients with PD.

This study used 6 patients all with advanced idiopathic PD. All were levodopa responders and showed moderate to severe symptoms and signs during the off state. Implantation of about 325000 RPE cells on microcarriers was performed. The results showed an average improvement of 48% at 12 months after implantation in the Unified Parkinson's Disease Rating Scale motor subscore with the patient in the off stat, which was sustained through 24 months. Improvement was also observed in activities of daily living, quality of life, and motor fluctuations. No off state dyskinesias were observed. Notable also is the persistent improvement in the percentage of on-state times, even in the presence of modest reductions in antiparkinsonian medications.

Conclusion of the study are the implants of human RPE cells attached to gelatin microcarriers appear to be safe and well tolerated, and they improve motor symptoms in patients with Parkinson Disease. The results of this study is a randomized, double-blind, placebo-controlled study.

Intrastriatal_Implantation_of_Human_Retinal_Pigment.pdf