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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. …

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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  • 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. 18F-DOPA PET
  • 3. 19
  • 4. 11C-Raclopride PET
  • 5. 11C-Raclopride PET + metamphetamine
  • 6. 11C-Raclopride PET
  • 7. 25
  • 8. Role of the serotonin system in L-DOPA-induced dyskinesia Carta et al., 2007
  • 9. Role of the serotonin system in L-DOPA-induced dyskinesia Carta et al., 2007
  • 10. Role of the grafted serotonin neurons on L-DOPA induced dyskinesia
  • 11. Role of the grafted serotonin neurons on L-DOPA induced dyskinesia Carlsson et al., 2007
  • 12. Role of the grafted serotonin neurons on L-DOPA induced dyskinesia Carlsson et al., 2007
  • 13. Role of the grafted serotonin neurons on L-DOPA induced dyskinesia Carlsson et al., 2007
  • 14. Online microdialysis Dopamine release        1st K+ 2nd K+  challenge challenge              
  • 15.   
  • 16.  
  • 17.      
  • 18.    
  • 19.  L-DOPA 
  • 20.                                                                                 Sahin et al., unpublished data
  • 21. 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
  • 22. How does the serotonin system respond to local continuous DOPA synthesis in the gene therapy setting? Carlsson et al., 2007
  • 23. Reversal of motor impairments after gene therapy Björklund et al., 2010
  • 24. 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