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

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

  • 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                                                                                 Sahin et al., unpublished data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