Open-label Investigation of the Safety and Clinical Effects of NTCELL in Patients With Parkinson's Disease
Condition: Parkinson's Disease
MeSH terms: Parkinson Disease
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      To assess the safety of xenotransplantation of NTCELL [immunoprotected
      (alginate-encapsulated) choroid plexus cells] in patients with Parkinson's disease, assessed
      over the duration of the study, by monitoring the occurrence of adverse events and serious
      adverse events, including clinical and laboratory evidence of xenogeneic infection in
      transplant recipients and their partners/close contacts. Subsequent safety follow-up will
      include lifelong monitoring for clinical and laboratory evidence of xenogeneic infection.

      To assess the clinical effects of NTCELL [immunoprotected (alginate-encapsulated) choroid
      plexus cells] in patients with Parkinson's disease. This will be quantified by testing the
      secondary endpoints of the trial as described below (see Endpoints/Outcome Measures).
    

Detailed description: 
      Parkinson's disease is characterized by widespread neural degeneration, particularly in the
      substantia nigra and its projections to the basal ganglia. Current therapy for Parkinson's
      disease is purely symptomatic. There is a pressing need for a treatment that reverses or
      slows the degeneration of the nigrostriatal pathway.

      Numerous transplant-based therapies have attempted to support, repair or replace the
      degenerating nigrostriatal neurons. These have included the transplantation of foetal and
      other neuronal stem cells, gene transfers, and the implantation of devices releasing neural
      growth factors. All these have been shown to have some effectiveness in animal models, but
      have been generally disappointing in human studies.

      Intracranial choroid plexus cell transplantation has the potential to deliver biological
      neural agents for the treatment of Parkinson's disease which cannot be achieved by
      conventional treatment. The overall aim of delivering neural proteins and compounds over many
      months to the basal ganglia of the brain is to enhance neural repair currently not possible
      with antiparkinsonian medication or deep brain stimulation (DBS).

      As animal-derived tissues have to be protected from immune rejection when transplanted into
      humans, transplants are usually accompanied by immunosuppressive therapy. However, porcine
      choroid plexus cells are preferably implanted without the use of immunosuppressive drugs
      which cause significant morbidity. To protect them from immune rejection, the cells can be
      encapsulated in alginate microcapsules which permit the inward passage of nutrients and the
      outward passage of biologic neural proteins and compounds normally secreted by choroid plexus
      cells. Alginate-encapsulated porcine choroid plexus cells implanted into the brain without
      immunosuppressive drugs have survived rejection for many months in animal studies.

      NTCELL comprises neonatal porcine choroid plexus cells encapsulated in alginate
      microcapsules. NTCELL has been safely implanted in rats, and non-human primates. Following
      NTCELL implants, animals with chemically-induced Parkinson's-like lesions showed improvement
      of functional neurological motor abnormalities that was associated with histologic changes
      consistent with amelioration of the lesion.

      The initial dose for intracranial implantation of the current NTCELL preparation for the
      treatment of Parkinson's disease in humans is based on the effective dose in a non-human
      primate (rhesus monkey) model.

      Parkinson's disease patients will be followed up for 26 weeks after receiving an implantation
      of NTCELL administered into the putamen of the corpus striatum on the side contralateral to
      the greatest clinical deficit.

      Based upon the data obtained during the 26-week follow-up period a decision will be made as
      to whether the patient will receive:

        -  an implantation of a second dose of NTCELL

        -  unilateral DBS

        -  bilateral DBS

        -  no further intervention

      The data will be reviewed by the investigators and the Data Safety Monitoring Board (DSMB),
      the data will consist of clinical outcomes and clinimetric data, an MRI scan, PET scanning,
      and adverse events.

      Patients will be followed up for a further 48 weeks if there is no further intervention,
      however if it is decided that either DBS or implantation of a second dose of NTCELL occurs
      then the frequency of follow-up will be the subject of a protocol amendment.
    

Intervention name(s): NTCELL
Intervention type(s): Other
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Parkinson's Disease; Xenotransplantation; choroid plexus