NTCell^®

Cellular therapy for Parkinson’s disease, Alzheimer’s disease, Huntington’s disease and stroke.

NTCell® is a choroid plexus cell product with the potential to treat degenerative diseases of the nervous system. These cells help produce cerebrospinal fluid as well as a range of neurotrophins (or nerve growth factors) that have been shown to protect against neuron (nerve) cell death in animal models of disease.

Product Demand

• Stroke is caused by an interruption of blood flow to the brain and is the third leading cause of death in most developed countries
• Stroke affects more than 48,000 Australians every year
• Stroke costs the Australian community over $630 million per year
• Parkinson’s disease is a neurological degenerative disorder that affects both body and mind. Together with Alzheimer’s disease, it represents the second most common brain disorder. Neither disease has a cure, and current treatment is unsatisfactory
• Huntington’s disease affects more than 1 in every 100,000 people. Each child of an affected parent has a 50% chance of inheriting the disease.
• There are over 1,200 people in Australia with Huntington’s disease and 6,000 more at risk.

Product Development

• NTCell® is well tolerated in pre-clinical primate studies targeting neurological disorders with no evidence of adverse side effects
• The treatment significantly diminishes the degeneration of striatal neurons in neurodegenerative conditions such as Huntington’s disease
• Pre-clinical results reveal the brain cell damage in primates treated with the NTCell® product was five times less than in control animals in a Huntington’s disease model
• Data from pre-clinical studies show that choroid plexus cell transplants can potentially reduce damage to the brain by 86% and dramatically improve limb use
• Early stage research indicates the product may be effective in protecting insulin secreting beta cells and preventing the onset of diabetes in a non-obese diabetic (NOD) mouse model of Type 1 diabetes.

NTCell® for other diseases

The secretions from NTCell® contain growth factors which have shown benefits in wound healing in animals. LCT is researching the development of a non-cell based product for wound healing.

These same secretions have a beneficial effect on the auditory nerve in individuals who are nerve deaf and have been implanted with a cochlear device. The success or otherwise of these devices rests on whether the new hearing device connects to the brain through the auditory nerve.

Animal experiments are being conducted to confirm the usefulness of this nerve regeneration using NTCell®.

Publications

• Skinner SJ, Geaney MS, Rush R, Rogers ML, Emerich DF, Thanos CG, Vasconcellos AV, Tan PL, Elliott RB.
  Choroid plexus transplants in the treatment of brain diseases.
  Xenotransplantation. 2006 Jul;13(4):284-8. Review. Read abstract

  Xenotransplantation. 2006 Jul;13(4):284-8.
  Choroid plexus transplants in the treatment of brain diseases.
  Skinner SJ, Geaney MS, Rush R, Rogers ML, Emerich DF, Thanos CG, Vasconcellos AV, Tan PL, Elliott RB.
  Living Cell Technologies Ltd, Auckland, New Zealand. sskinner@lctglobal.com

  The choroid plexus (CP) produces and secretes numerous biologically active neurotrophic factors into the cerebrospinal fluid (CSF). These circulate throughout the brain and spinal cord, maintaining neuronal networks and associated cells. In neurodegenerative disease and in acute brain injury there is local up-regulation of neurotrophin production close to the site of the lesion. Treatment by direct injection of neurotrophins and growth factors close to these lesion sites has repeatedly been demonstrated to improve recovery. It has therefore been proposed that transplanting viable choroid plexus cells close to the lesion might provide a novel means for continuous delivery of these molecules directly to the site of injury. Recent publications describe how transplanted CP, either free or in an immunoprotected encapsulated form, deliver therapeutic molecules to the desired site. This review briefly describes the accumulated evidence that CP cells support neuronal cells in vitro and have therapeutic properties when transplanted to treat acute and chronic brain disease and injury in animal models.

• Borlongan CV, Skinner SJ, Geaney M, Vasconcellos AV, Elliott RB, Emerich DF.
  Neuroprotection by encapsulated choroid plexus in a rodent model of Huntington's disease.
  Neuroreport. 2004 Nov 15;15(16):2521-5. Read abstract

  Neuroreport. 2004 Nov 15;15(16):2521-5.
  Neuroprotection by encapsulated choroid plexus in a rodent model of Huntington's disease.
  Borlongan CV, Skinner SJ, Geaney M, Vasconcellos AV, Elliott RB, Emerich DF.
  Neurology Department, Institute of Mol Med and Genetics and School of Graduate Studies, Medical College, 1120 15th Street, Augusta, GA 30912-3200, USA. cborlongan@mail.mcg.edu

  Choroid plexus from neonatal pigs was encapsulated in alginate microcapsules and transplanted into the rat striatum. Three days later, the same animals received unilateral injections of quinolinic acid (225 nmol) into the ipsilateral striatum. Choroid plexus transplants ameliorated the weight loss and motor impairments resulting from QA. Histological analysis demonstrated that choroid plexus transplants reduced the volume of striatal damage and protected ChAT-, but not NADPH-diaphorase-positive neurons. These data are the first to demonstrate that transplanted choroid plexus cells can protect striatal neurons from excitotoxic damage and that this strategy may ultimately prove relevant for the treatment of Huntington's disease.

• Borlongan CV, Skinner SJ, Geaney M, Vasconcellos AV, Elliott RB, Emerich DF.
  Intracerebral transplantation of porcine choroid plexus provides structural and functional neuroprotection in a rodent model of stroke.
  Stroke. 2004 Sep;35(9):2206-10. Epub 2004 Jul 29. Read abstract

  Stroke. 2004 Sep;35(9):2206-10. Epub 2004 Jul 29
  Intracerebral transplantation of porcine choroid plexus provides structural and functional neuroprotection in a rodent model of stroke. Borlongan CV, Skinner SJ, Geaney M, Vasconcellos AV, Elliott RB, Emerich DF.
  Department of Neurology, School of Medicine, and the Institute of Molecular Medicine and Genetics, School of Graduate Studies, Medical College of Georgia, Augusta, Ga 30912-3200, USA. cborlongan@mail.mcg.edu

  BACKGROUND AND PURPOSE: Choroid plexus (CP) secretes a cocktail of neurotrophic factors. In the present study, CP from neonatal pigs was encapsulated within alginate microcapsules for in vitro and in vivo neuroprotective studies.

  METHODS: In vitro studies involved serum deprivation of rat embryonic cortical neurons and treatment with a range of concentrations of conditioned media from CP. For in vivo studies, rats received a 1-hour middle cerebral artery occlusion followed by intracranial transplantation of encapsulated or unencapsulated CP, empty capsules, or no transplant. Behavioral testing was conducted on days 1 to 3 after transplantation. Cerebral infarction was analyzed using 2,3,5-triphenyl-tetrazolium chloride staining at 3 days after transplantation.

  RESULTS: Conditioned media from CP produced a significant dose-dependent protection of serum-deprived cortical neurons. Enzyme-linked immunosorbent assay confirmed secretion of GDNF, BDNF, and NGF from CP. Parallel in vivo studies showed that CP transplants improved behavioral performance and decreased the volume of infarction. Both encapsulated and unencapsulated CP transplants were effective; however, more robust benefits accompanied encapsulated transplants.

  CONCLUSIONS: These data are the first to demonstrate the neuroprotective potential of transplanted CP and raise the intriguing possibility of using these cells as part of the treatment regimen for stroke and other neurological disorders.

• Emerich DF, Vasconcellos AV, Elliott RB, Skinner SJ, Borlongan CV.
  The choroid plexus: function, pathology and therapeutic potential of its transplantation.
  Expert Opin Biol Ther. 2004 Aug;4(8):1191-201. Review. Read abstract

  Expert Opin Biol Ther. 2004 Aug;4(8):1191-201
  The choroid plexus: function, pathology and therapeutic potential of its transplantation.
  Emerich DF, Vasconcellos AV, Elliott RB, Skinner SJ, Borlongan CV.
  LCT BioPharma, 766 Laten Knight Rd, Cranston, RI 02921, USA. ED3FJM@aol.com

  The choroid plexus (CP) produces cerebrospinal fluid (CSF) and forms the blood-CSF barrier. However, the CP may have additional functions in the CNS beyond these traditional roles. Preclinical and clinical studies in ageing and neurodegeneration demonstrate anatomical and physiological changes in CP, suggesting roles in normal and pathological conditions and potentially endogenous repair processes following trauma. One of the broadest functions of the CP is establishing and maintaining the extracellular milieu throughout the brain and spinal cord, in part by secreting numerous growth factors into the CSF. The endogenous secretion of growth factors raises the possibility that transplantable CP might enable delivery of these molecules to the brain, while avoiding the conventional molecular and genetic alterations associated with modifying cells to secrete selected products. This review describes some of the anatomical and functional changes of CP in ageing and neurodegeneration, and recent demonstrations of the therapeutic potential of transplanted CP for neural trauma.