Edith Cowan University
Parkinsons Centre

People

Dr Roger Barker

Research Interests

Dr Barker’s research comprises four major areas of interest. Two of these involve clinically based projects and two involve cell-based therapies including xenografts (ie the transplantation of tissue from one species to another) and stem cells.

1) Parkinson's Disease Clinical Research: Dr Barker established a Parkinson's Disease Research Clinic at the Cambridge Centre for Brain Repair, which is recruiting all cases of Parkinsonism in the East Anglia region. This includes an incident cohort that was collected between 2002 and 2002 and totals around 160 patients, along with a prevalent cohort of 600 to 700 patients, all of whom are being followed longitudinally. The main aim of this study is to define the different type of Parkinson's and their neurobiological basis and involves assessing patients clinically, blood sampling with DNA analysis looking for genetic risk factors, along with functional imaging and ultimately post mortem analysis of the brains.

In collaboration with a number of centres, this project has so far defined that there appear to be different groups of Parkinson's both clinically and on functional imaging. In addition, we have also started to identify genetic risk factors as well as disease modifying genes that impinge and influence these different clinical phenotypes.

Dr Barker strongly supports the ECU Parkinson’s Centre (ParkC) and collaborates with ParkC in comparative studies that identify different subtypes of Parkinson’s.

2) Huntington's Disease Clinical Research: Research into Huntington's disease in Cambridge goes back a decade and has been facilitated by the establishment of the regional clinic in the mid 1990's, and since 2000 Dr Barker has become the neurology consultant in charge of this clinic which sees between 200 and 250 patients. A cohort of these patients have been selected to be part of a UK Consortium looking at neural transplantation for the treatment of their condition and so far this has involved bilateral striatal transplants in five patients with mild to moderate disease. Whilst the safety of the procedure has been proven the efficacy is as yet unknown. The large group of patients has also enabled a number of other studies to be developed in collaboration with a number of other groups including the neuropsychology of Huntington's disease, its evolution over time, as well as the search for new biomarkers of disease. The clinical work in Huntington's disease has of late been greatly facilitated by the collaboration of our group with Jenny Morton in the Department of Pharmacology. Dr Morton has extensive experience with transgenic mouse models of HD which will facilitate the translation of drug therapies from the lab into the clinic as and when data dictates.

3) Xenotransplantation: Over the last five to six years Dr Barker’s group has developed a programme investigating the immunology and functional capacity of xenotransplantated tissue in animal models of neurodegenerative disorder. During this period of time we have investigated basic aspects of embryonic porcine neural xenotransplants - including their rejection profile in the non-immunosupressed rat. In addition, we have isolated and grown porcine neural stem cells and investigated their potential for circuit repair, along with their rejection properties. We have also described the immunogenic epitopes expressed by this tissue, and the expression of complement regulatory proteins in transgenic tissue. In addition, there appear to be properties of xenografted tissue which are different from that in the allograft situation, including cell migration and axonal growth. We are therefore exploring these aspects of xenograft behaviour.

4) Stem Cells: Finally, Dr Barker’s group over the last few years has investigated neural stem cells. This has not only involved better characterisation of porcine embryonic neural precursor cells but the differentiation and repair properties of embryonic human fetal neural precursor cells. Of late the emphasis in the group has changed to look at the endogenous neural stem cell and its behaviour in the neural degenerative brain. In particular Dr Barker is interested in the properties of these cells and their failure to repair the brain in the face of progressive chronic cell loss as occurs in Parkinson's and Huntington's disease. This is being explored using transgenic models of the disease. This work has involved collaborations with Jenny Morton in the Department of Pharmacology with the transgenic mouse model of Huntington's disease.

Selected Publications

  1. Barker, R.A. and A.P. Cahn, Parkinson's disease: an autoimmune process. Int J Neurosci, 1988. 43(1-2): p. 1-7.
  2. Barker, R.A. and A.E. Rosser, Neural transplantation therapies for Parkinson's and Huntington's diseases. Drug Discov Today, 2001. 6(11): p. 575-582.
  3. Barker, R.A., Repairing the brain in Parkinson's disease: where next? Mov Disord, 2002. 17(2): p. 233-41.
  4. Foltynie, T., C. Brayne, and R.A. Barker, The heterogeneity of idiopathic Parkinson's disease. J Neurol, 2002. 249(2): p. 138-45.
  5. Foltynie, T., et al., The genetic basis of Parkinson's disease. J Neurol Neurosurg Psychiatry, 2002. 73(4): p. 363-70.
  6. Armstrong, R.J., et al., Transplantation of expanded neural precursor cells from the developing pig ventral mesencephalon in a rat model of Parkinson's disease. Exp Brain Res, 2003. 151(2): p. 204-17.
  7. Bjorklund, A., et al., Neural transplantation for the treatment of Parkinson's disease. Lancet Neurol, 2003. 2(7): p. 437-45.
  8. Lewis, S.J., et al., Using executive heterogeneity to explore the nature of working memory deficits in Parkinson's disease. Neuropsychologia, 2003. 41(6): p. 645-54.
  9. Lewis, S.J., et al., Cognitive impairments in early Parkinson's disease are accompanied by reductions in activity in frontostriatal neural circuitry. J Neurosci, 2003. 23(15): p. 6351-6.
  10. Barker, R.A. and T. Foltynie, The future challenges in Parkinson's disease. J Neurol, 2004. 251(3): p. 361-5.
  11. Foltynie, T., et al., The cognitive ability of an incident cohort of Parkinson's patients in the UK. The CamPaIGN study. Brain, 2004. 127(Pt 3): p. 550-60.
  12. Hurelbrink, C.B. and R.A. Barker, The potential of GDNF as a treatment for Parkinson's disease. Exp Neurol, 2004. 185(1): p. 1-6.
  13. Lewis, S.J., et al., Heterogeneity of Parkinson's disease in the early clinical stages using a data driven approach. J Neurol Neurosurg Psychiatry, 2005. 76(3): p. 343-8.
  14. Barker, R.A., Continuing trials of GDNF in Parkinson's disease. Lancet Neurol, 2006. 5(4): p. 285-6.
  15. Harrower, T.P., et al., Long-term survival and integration of porcine expanded neural precursor cell grafts in a rat model of Parkinson's disease. Exp Neurol, 2006. 197(1): p. 56-69.
  16. Healy, D.G., et al., UCHL-1 is not a Parkinson's disease susceptibility gene. Ann Neurol, 2006. 59(4): p. 627-33.
  17. Jain, M., et al., Transplanted human neural precursor cells migrate widely but show no lesion-specific tropism in the 6-hydroxydopamine rat model of Parkinson's disease. Cell Transplant, 2006. 15(7): p. 579-93.
  18. Kuan, W.L., C.B. Hurelbrink, and R.A. Barker, Increased capacity for axonal outgrowth using xenogenic tissue in vitro and in a rodent model of Parkinson's disease. Xenotransplantation, 2006. 13(3): p. 233-47.
  19. Michell, A.W., et al., Saccadic latency distributions in Parkinson's disease and the effects of L-dopa. Exp Brain Res, 2006. 174(1): p. 7-18.
  20. Slabosz, A., et al., The role of learned irrelevance in attentional set-shifting impairments in Parkinson's disease. Neuropsychology, 2006. 20(5): p. 578-88.
  21. Swainson, R., et al., Impaired dimensional selection but intact use of reward feedback during visual discrimination learning in Parkinson's disease. Neuropsychologia, 2006. 44(8): p. 1290-304.
  22. Williams-Gray, C.H., et al., Cognitive deficits and psychosis in Parkinson's disease: a review of pathophysiology and therapeutic options. CNS Drugs, 2006. 20(6): p. 477-505.
  23. Williams-Gray, C.H., et al., Prevalence of the LRRK2 G2019S mutation in a UK community based idiopathic Parkinson's disease cohort. J Neurol Neurosurg Psychiatry, 2006. 77(5): p. 665-7.
  24. Williams-Gray, C.H., et al., No alterations in alpha-synuclein gene dosage observed in sporadic Parkinson's disease. Mov Disord, 2006. 21(5): p. 731-2.
  25. Cools, R., et al., L-DOPA disrupts activity in the nucleus accumbens during reversal learning in Parkinson's disease. Neuropsychopharmacology, 2007. 32(1): p. 180-9.
  26. Goris, A., et al., Tau and alpha-synuclein in susceptibility to, and dementia in, Parkinson's disease. Ann Neurol, 2007. 62(2): p. 145-53.
  27. Goris, A., et al., Investigation of TGFB2 as a candidate gene in multiple sclerosis and Parkinson's disease. J Neurol, 2007. 254(7): p. 846-8.
  28. Goya, R.L., W.L. Kuan, and R.A. Barker, The future of cell therapies in the treatment of Parkinson's disease. Expert Opin Biol Ther, 2007. 7(10): p. 1487-98.
  29. Lawrence, A.J., et al., Predictors of punding in Parkinson's disease: results from a questionnaire survey. Mov Disord, 2007. 22(16): p. 2339-45.
  30. Michell, A.W., et al., The effect of truncated human alpha-synuclein (1-120) on dopaminergic cells in a transgenic mouse model of Parkinson's disease. Cell Transplant, 2007. 16(5): p. 461-74.
  31. Williams-Gray, C.H. and R.A. Barker, Visual hallucinations predict increased benefits from rivastigmine in Parkinson's disease dementia. Nat Clin Pract Neurol, 2007. 3(5): p. 250-1.
  32. Williams-Gray, C.H., et al., Evolution of cognitive dysfunction in an incident Parkinson's disease cohort. Brain, 2007. 130(Pt 7): p. 1787-98.
  33. Williams-Gray, C.H., et al., Catechol O-methyltransferase Val158Met genotype influences frontoparietal activity during planning in patients with Parkinson's disease. J Neurosci, 2007. 27(18): p. 4832-8.
  34. Antoniades, C.A. and R.A. Barker, The search for biomarkers in Parkinson's disease: a critical review. Expert Rev Neurother, 2008. 8(12): p. 1841-52.
  35. Evans, J.R. and R.A. Barker, Neurotrophic factors as a therapeutic target for Parkinson's disease. Expert Opin Ther Targets, 2008. 12(4): p. 437-47.
  36. Foltynie, T., et al., BDNF val66met Influences Time To Onset Of Levodopa-Induced Dyskinesia In Parkinson's Disease. J Neurol Neurosurg Psychiatry, 2008.
  37. Kuan, W.L., J.W. Zhao, and R.A. Barker, The role of anxiety in the development of levodopa-induced dyskinesias in an animal model of Parkinson's disease, and the effect of chronic treatment with the selective serotonin reuptake inhibitor citalopram. Psychopharmacology (Berl), 2008. 197(2): p. 279-93.
  38. Laguna Goya, R., P. Tyers, and R.A. Barker, The search for a curative cell therapy in Parkinson's disease. J Neurol Sci, 2008. 265(1-2): p. 32-42.
  39. Lewis, S.J. and R.A. Barker, A pathophysiological model of freezing of gait in Parkinson's disease. Parkinsonism Relat Disord, 2008.
  40. Rowe, J.B., et al., Parkinson's disease and dopaminergic therapy--differential effects on movement, reward and cognition. Brain, 2008. 131(Pt 8): p. 2094-105.
  41. Rowe, J.B., et al., The val(158)met COMT polymorphism's effect on atrophy in healthy aging and Parkinson's disease. Neurobiol Aging, 2008.
  42. Wijeyekoon, R. and R.A. Barker, Cell replacement therapy for Parkinson's disease. Biochim Biophys Acta, 2008.
  43. Williams-Gray, C.H., et al., Attentional control in Parkinson's disease is dependent on COMT val 158 met genotype. Brain, 2008. 131(Pt 2): p. 397-408.