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 2: http://www.slideshare.net/ParkinsonsResearchUK/cell-and-gene-therapy-for-parkinsons-disease-part-2. Part 3: http://www.slideshare.net/ParkinsonsResearchUK/cell-and-gene-therapy-for-parkinsons-disease-part-3

1. Cell and gene therapy for Parkinson’s disease
Deniz Kirik, MD, PhD
Professor of Neuroscience
Brain Repair And Imaging in Neural Systems (BRAINS) Unit
Department of Experimental Medical Science
Lund University, Sweden

2. Major symptoms of Parkinson’s disease
• Difficulty to initiate movement
• Slowness of movement
• Stiffness
• Shaking at rest
• Postural imbalance

3. Parkinson’s disease is characterized by degeneration of
dopamine producing cells located in the substantia nigra

4. Parkinson’s disease is characterized by degeneration of
dopamine producing cells located in the substantia nigra

5. Kirik et al., 2005

6. Threshold dose of L-DOPA for inducing dyskinesia
decreases over duration of the disease
1.8
1.2
L-dopa level (mg/kg)
0.8
0.4
0
Never Stable Wearing-o On-o
treated responders
(n=8) (n=6) (n=13) (n=12)
Mouradian et al. 1987

7. Restorative treatment strategy for PD
No of DA neurons
Onset of
symptoms
Functional
recovery
Disease
progression
Restorative therapy

8. Striatal dopamine replacement strategy by fetal nigral
dopamine neurons
Parkinson’s Disease Fetal nigral transplantation
Input
Input
Response Response
Motor Motor
output output

9. Gene therapy for DOPA delivery
Carlsson et al., 2007

10. Fetal Cell Transplantation Procedure
Ventral
mesencephalon
Transplantation
Trypsin/DNase Mechanical
dissociation

11. Fetal Cell Transplantation Procedure
Thompson et al., 2005

12. Transplantation of human fetal DA neuroblasts
Mendez et al., 2005

13. Grafts of fetal dopamine neurons survive and improve motor
function in Parkinson's disease
Lindvall et al., Science 1990

14. History of Cell Transplantation in Parkinson's Disease
1979: First reports of functional restoration in
rodent models of PD
1990: First report of therapeutic effects in PD patients
in open-label trials
2001: Reports of the first placebo-controlled
double-blind studies