TY - JOUR
T1 - Intrastriatal transplantation of microcarrier-bound human retinal pigment epithelial cells versus sham surgery in patients with advanced Parkinson's disease
T2 - A double-blind, randomised, controlled trial
AU - Gross, Robert E.
AU - Watts, Raymond L.
AU - Hauser, Robert A.
AU - Bakay, Roy A.E.
AU - Reichmann, Heinz
AU - von Kummer, Rüdiger
AU - Ondo, William G.
AU - Reissig, Elke
AU - Eisner, Wilhelm
AU - Steiner-Schulze, Heike
AU - Siedentop, Harald
AU - Fichte, Klaus
AU - Hong, Walter
AU - Cornfeldt, Michael
AU - Beebe, Katherine
AU - Sandbrink, Rupert
N1 - Funding Information:
REG, RLW, RAH, RAEB, and WGO have received funding from Schering AG (now Bayer HealthCare Pharmaceuticals). We thank the members of the independent data monitoring committee, Donald B Calne, Andres M Lozano, Wolfgang Oertel, C Warren Olanow, and John Petkau for analysis of safety data, making decisions on the conduct of the study, contributions to the study protocol and its modification, and review of the paper. We thank also Lee Howell, Executive VP for Medical Affairs, and Margaret Callahan, Senior Medical Editor, Precept Medical Communications, for providing editorial assistance in the preparation of the manuscript.
PY - 2011/6
Y1 - 2011/6
N2 - Background: 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. Methods: 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. Findings: 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. Interpretation: Transplantation of human RPE cells provided no antiparkinsonian benefits compared with sham surgery. Funding: Bayer HealthCare AG.
AB - Background: 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. Methods: 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. Findings: 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. Interpretation: Transplantation of human RPE cells provided no antiparkinsonian benefits compared with sham surgery. Funding: Bayer HealthCare AG.
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UR - http://www.scopus.com/inward/citedby.url?scp=79956077225&partnerID=8YFLogxK
U2 - 10.1016/S1474-4422(11)70097-7
DO - 10.1016/S1474-4422(11)70097-7
M3 - Article
C2 - 21565557
AN - SCOPUS:79956077225
VL - 10
SP - 509
EP - 519
JO - The Lancet Neurology
JF - The Lancet Neurology
SN - 1474-4465
IS - 6
ER -