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

Parkinsonism Relat Disord. 2019 Apr:61:88-93. doi: 10.1016/j.parkreldis.2018.11.015. Epub 2018 Nov 13.

Abstract

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®) to protect them from immune attack. NTCELL® 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® in human subjects, we sought to specifically investigate the safety and efficacy of NTCELL® 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® (the 3 groups in the treatment arm receiving incremental NTCELL® 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® 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® implantation was safe and well tolerated.

Keywords: Choroid plexus; Dopaminergic neurons; Nerve growth factors; Parkinson's disease; Xenotransplantation.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alginates
  • Animals
  • Cell Encapsulation*
  • Cell Transplantation / methods*
  • Choroid Plexus / cytology*
  • Choroid Plexus / metabolism
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neostriatum*
  • Nerve Growth Factors / metabolism
  • Parkinson Disease / therapy*
  • Swine
  • Transplantation, Heterologous
  • Treatment Outcome

Substances

  • Alginates
  • Nerve Growth Factors