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Human retinal pigment epithelial (RPE) cells produce levodopa and their transplantation into the striatum might improve continuity of administration compared with that achieved with oral levodopa. We aimed to assess the safety, tolerability, and efficacy of transplantation of microcarrier-bound human RPE cells versus a sham surgery control in patients with advanced Parkinson's disease. In this randomised, double-blind study eligible patients were aged 36–70 years, had been symptomatic for at least 5 years, were in Hoehn and Yahr stage 3–4 and had unified Parkinson's disease rating scale (UPDRS) motor scores of 38–70 when off medication (off state), and had symptoms that responded to oral levodopa but were insufficiently controlled by optimised pharmacotherapy. Randomisation was done in a 1:1 ratio. Only the neurosurgical team was aware of treatment assignments. During stereotactic transplantation around 325 000 cells per side were injected into the postcommissural putamen; sham surgery patients received partial burr holes. The primary efficacy endpoint was change in UPDRS off-state motor score at 12 months. This study is registered with ClinicalTrials.gov, number NCT00206687. Of 71 enrolled patients, 35 underwent cell transplantation and 36 sham surgery. Change in mean motor scores did not differ significantly between groups (−10·5 [SD 10·26] for transplantation vs −10·1 [SD 12·26] for sham surgery, p=0·9). The overall rate of adverse events was similar in the two study groups, although the number attributable to surgery or RPE cells (mostly neurological or psychiatric) was higher in transplant recipients. Two and seven patients died in the sham surgery and transplantation group, respectively; one death in the latter group was possibly related to surgery or RPE cells. Transplantation of human RPE cells provided no antiparkinsonian benefits compared with sham surgery. Bayer HealthCare AG.

Intrastriatal transplantation of gelatin microcarrier-attached human retinal pigment epithelial cells (hRPE-GM) may represent an alternative source for cell therapy in Parkinson disease (PD). The use of human retinal pigment epithelial (hRPE) cells in PD relies on the capacity of these cells to produce l-dopa as an intermediate product in the eumelanin synthesis pathway. We investigated the behavioral effects of hRPE-GM implants on forelimb use asymmetries and hindlimb motor deficits in unilateral and bilateral 6-hydroxydopamine (6-OHDA) rat models of PD. We report that intrastriatal unilateral implantation of hRPE-GM in rats with 6-OHDA nigrostriatal lesions produce an amelioration of the contralateral forelimb disuse and the contralateral hindlimb deficits. These results further support the possibility that implantation of cultured hRPE cells may be a promising therapeutic option for patients with PD.

Previous studies have demonstrated that the intrastriatal implantation of human retinal pigment epithelial cells attached to gelatin microcarriers (hRPE-GM) ameliorates behavioral deficits in animal models of Parkinson disease. However, there are only sparse data on cell survival in the host. In this study, we characterized a variety of retinal pigment epithelial (RPE)-specific markers in vitro and used these markers to investigate the long-term survival of hRPE-GM implants. Sprague-Dawley rats (n = 22) were unilaterally lesioned with 6-hydroxydopamine (6-OHDA) and implanted with hRPE-GM without immunosuppression. Rats were euthanized at 48 hours, 7 days, 4 weeks, and 5 months postimplant and immunohistochemically processed using the following antibodies1) human-specific nuclear mitotic apparatus protein (NuMA-Ab2), 2) epithelial-specific extracellular matrix metalloproteinase inducer (EMMPRIN), 3) RPE cell-specific RPE65, and the inflammation markers 4) glial fibrillary acidic protein and 5) ED1 (rat CD68). Our analysis revealed NuMA-, EMMPRIN-, and RPE65-immunoreactive cells at different times postimplant. The morphologic features of hRPE cell implants (at 48 hours and 5 months) were confirmed by electron microscopy. Furthermore, despite evidence of chronic inflammation at the later time point, there is an appreciable number of surviving hRPE cells. This study suggests that hRPE-GM implants can survive in the absence of immunosuppression and can be potentially used as an alternative for treating Parkinson disease.