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, HR, and RvK have received consulting fees, honoraria, and funding for travel from Bayer HealthCare Pharmaceuticals, and RAH, HR, RvK have received fees for reviewing activities. ER, HS-S, HS, KF, WH, and RS were employees of Bayer HealthCare AG, and MC and KB were employees of Titan Pharmaceuticals. RS has stock or stock options with Bayer Healthcare. Other relevant activities not directly related to the present work are as follows. RAH serves on the advisory boards of Boehringer Ingelheim, Teva Neuroscience, Impax Pharmaceuticals, UCB Pharma, GE Healthcare, IPSEN Pharmaceuticals, Novartis, Parkinson Study Group, Solvay, Quintiles, and Biogen Idec. REG acts as a consultant for Boston Scientific, St Judes Medical Corp., GeneGrafts, RAH as a consultant for Biogen Idec, Boehringer Ingelheim, Chelsea Therapeutics, GE Healthcare, Impax, Santhera Pharmaceuticals, Merck Serono/EMD Serono, Solvay Pharmaceuticals, Synosia Therapeutics, Schering-Plough, Shire Pharmaceuticals, XenoPort, Medivation, and HR for Boehringer Ingelheim, Abbott, Bayer Healthcare, Cephalon, Desitin, GlaxoSmithKline, Lilly, Pfizer, UCB, Novartis/Orion, Teva/Lundbeck. RAH has received grants from Schwartz Pharma, Genzyme, Acadia, Solvay Pharmaceuticals, Impax, TEVA Neuroscience, Merck/Serono, Schering-Plough, Novartis Pharmaceuticals, IPSEN Pharmaceuticals, XenoPort Pharmaceuticals, Chelsea Therapeutics, Allergan Neuroscience, Molecular Biometrics, The Michael J Fox Foundation for Parkinson's Research, and the National Parkinson Foundation, and HR from Pfizer, Desitin, and UCB. REG received payments for lectures, from Medtronic, RAH and HR from GlaxoSmithKline, Teva Neuroscience, Boehringer Ingelheim, and RAH from Allergan Neuroscience, Novartis Pharmaceuticals, IPSEN Pharmaceuticals Abbott, Bayer Healthcare, Cephalon, Desitin, Lilly, Pfizer, UCB Pharma, and Orion. Patents are held by MC from Titan Pharmaceuticals. RAH has received royalties from the University of South Florida, USA. REG has received payment for development of educational materials from Medtronic, and HR from Lundbeckand Desitin. WE and KF declare that they have no conflicts of interest.
Funding Information:
The study was funded and overseen by, and writing support was provided by Berlex and Schering AG (now Bayer HealthCare AG). Data management and analyses were coordinated by the sponsors and they contributed to the study design, conduct, and reporting. All authors had full access to all data in the study and had final responsibility for the decision to submit for publication.
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.
Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
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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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 -