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