Cell and gene therapy for Parkinson’s disease - part 1
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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
Major symptoms of Parkinson’s disease
• Difficulty to initiate movement
• Slowness of movement
• Stiffness
• Shaking at rest
• Postural imbalance
Parkinson’s disease is characterized by degeneration of
dopamine producing cells located in the substantia nigra
Parkinson’s disease is characterized by degeneration of
dopamine producing cells located in the substantia nigra
Kirik et al., 2005
Threshold dose of L-DOPA for inducing dyskinesia
decreases over duration of the disease
Mouradian et al. 1987
L-d
op
a le
ve
l (m
g/k
g)
0.4
0
0.8
1.2
1.8
Never
treated
(n=8)
Stable
responders
(n=6)
Wearing-o
(n=13)
On-o
(n=12)
Restorative treatment strategy for PD
Disease
progression
Functional
recovery
Restorative therapy
Onset of
symptoms
No of DA neurons
Striatal dopamine replacement strategy by fetal nigral
dopamine neurons
Fetal nigral transplantationParkinson’s Disease
Input
Response
Motoroutput
Input
Response
Motoroutput
Carlsson et al., 2007
Gene therapy for DOPA delivery
Ventral
mesencephalon
Trypsin/DNase Mechanical
dissociation
Transplantation
Fetal Cell Transplantation Procedure
Fetal Cell Transplantation Procedure
Thompson et al., 2005
Transplantation of human fetal DA neuroblasts
Mendez et al., 2005
Grafts of fetal dopamine neurons survive and improve motor
function in Parkinson's disease
Lindvall et al., Science 1990
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
History of Cell Transplantation in Parkinson's Disease