A phase IIb, randomised, double-blind, placebo-controlled, dose-ranging investigation of the safety and efficacy of NTCELL® [immunoprotected (alginate-encapsulated) porcine choroid plexus cells for xenotransplantation] in patients with Parkinson's disease

Introduction: Regenerative therapies in Parkinson's disease aim to slow neurodegeneration and re-establish damaged neuronal circuitry. Neurotrophins are potent endogenous regulators of neuronal survival, development and regeneration. They represent an attractive regenerative treatment option in Parkinson's disease. Porcine choroid plexus produces a number of neurotrophins, and can be safely delivered to the striatum in an encapsulated formulation (termed NTCELL (R)) to protect them from immune attack. NTCELL (R) has shown regenerative potential in animal models of stroke, Huntington's disease and Parkinson's disease. Following promising results from an initial open label safety study of intra-striatal delivery of NTCELL (R) in human subjects, we sought to specifically investigate the safety and efficacy of NTCELL (R) for the treatment of Parkinson's disease. Methods: 18 patients aged 56-65 years with idiopathic Parkinson's disease of at least 5 years duration were randomised to receive either sham surgery (general anaesthesia and partial thickness burr holes) or intra-striatal delivery of NTCELL (R) (the 3 groups in the treatment arm receiving incremental NTCELL (R) doses). Results: At 26 weeks, we found no significant difference in total UPDRS scores ('on' and 'off'), UPDRS motor scores ('on' and 'off), PDQ-39, UDysRS, timed walk or modified Hoehn and Yahr stage between patients implanted with NTCELL (R) and patients undergoing sham procedure. There were no serious adverse events or xenogeneic viral transmission during the study. Conclusion: The study did not meet its primary efficacy end-point of a change in UPDRS at 26 weeks post intervention compared with baseline. Stereotactic NTCELL (R) implantation was safe and well tolerated.