Cell and gene therapy for Parkinson’s disease - part 2

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Presentation by Prof Deniz Kirik, MD, PhD at the Parkinson's UK Research Conference, November 2010 in York.

With introduction by Dr Oliver Bandmann.

Part 1: http://www.slideshare.net/ParkinsonsResearchUK/cell-and-gene-therapy-for-parkinsons-disease-part-1

Published in: Health & Medicine, Technology
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Cell and gene therapy for Parkinson’s disease - part 2

  1. 1. Results of the clinical trials Good therapeutic effect requires: - ~100 000 surviving DA-neurons on each side - Recovery of putaminal FD-uptake to ~50% of normal - Reinnervation of a major part of the striatal volume Problems associated with cell transplantation: - the results are too variable - the delayed immune response must be controlled - graft-induced dyskinesia is a problem that must be solved - the use of fetal tissue is unsatisfactory
  2. 2. 18F-DOPA PET
  3. 3. 19
  4. 4. 11C-Raclopride PET
  5. 5. 11C-Raclopride PET + metamphetamine
  6. 6. 11C-Raclopride PET
  7. 7. 25
  8. 8. Role of the serotonin system in L-DOPA-induced dyskinesia Carta et al., 2007
  9. 9. Role of the serotonin system in L-DOPA-induced dyskinesia Carta et al., 2007
  10. 10. Role of the grafted serotonin neurons on L-DOPA induced dyskinesia
  11. 11. Role of the grafted serotonin neurons on L-DOPA induced dyskinesia Carlsson et al., 2007
  12. 12. Role of the grafted serotonin neurons on L-DOPA induced dyskinesia Carlsson et al., 2007
  13. 13. Role of the grafted serotonin neurons on L-DOPA induced dyskinesia Carlsson et al., 2007
  14. 14. Online microdialysis Dopamine release 1st K+ 2nd K+ challenge challenge
  15. 15. L-DOPA
  16. 16. Sahin et al., unpublished data
  17. 17. Dyskinesias induced by serotonergic hyperinnervation in the grafted striatum are effectively suppressed by a 5-HT1A agonist in transplanted PD patients Politis et al., 2010
  18. 18. How does the serotonin system respond to local continuous DOPA synthesis in the gene therapy setting? Carlsson et al., 2007
  19. 19. Reversal of motor impairments after gene therapy Björklund et al., 2010
  20. 20. Reversal of dyskinesia after gene therapy L-DOPA induced dyskinesias 300 Integrated AIM score 200 100 * * 0 Pre 4 8 12 Viral Injection Weeks AIM = Abnormal involuntary movement Carlsson et al., 2005

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