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24 - Necessary methodological and stem cell advances for restoration of the dopaminergic system in Parkinson's disease patients

from Part III - Therapeutic approaches in neurodegeneration

Published online by Cambridge University Press:  04 August 2010

M. Flint Beal ,
Anthony E. Lang  and
Albert C. Ludolph
By
Ole Isacson ,
Kwang-Soo Kim ,
Ivar Mendez ,
Craig van Horne ,
Lars M. Bjorklund  and
Rosario Sanchez-Pernaute
M. Flint Beal
Affiliation:
Cornell University, New York
Anthony E. Lang
Affiliation:
University of Toronto
Albert C. Ludolph
Affiliation:
Universität Ulm, Germany
Ole Isacson
Affiliation:
Udall Parkinson's Disease Research Center of Excellence, Belmont, MA, USA
Kwang-Soo Kim
Affiliation:
Udall Parkinson's Disease Research Center of Excellence, Belmont, MA, USA
Ivar Mendez
Affiliation:
Division of Neurosurgery, Dalhousie University, Halifax, NS, Canada
Craig van Horne
Affiliation:
Udall Parkinson's Disease Research Center of Excellence, Belmont, MA, USA
Lars M. Bjorklund
Affiliation:
Udall Parkinson's Disease Research Center of Excellence, Belmont, MA, USA
Rosario Sanchez-Pernaute
Affiliation:
Udall Parkinson's Disease Research Center of Excellence, Belmont, MA, USA
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Summary

Introduction

New therapeutic non-pharmacological methodology involves cell and synaptic renewal or replacement in the living brain to restore function of neuronal systems, including the dopaminergic (DA) system in Parkinson's disease. Understanding the cell biological principles for generating functional DA neurons in lieu of the diseased can provide many new avenues for better treatment of patients with PD. Recent laboratory work has focused on using stem cells as a starting point for exogenous or endogenous derivation of the optimal DA cells for repair (Fig. 24.1). Using fetal DA cell therapy in PD patients (Piccini et al., 1999, 2000; Freed et al., 2001; Isacson et al., 2001; Mendez et al., 2002a) and stem cell-derived DA neurons in animal models (Bjorklund et al., 2002; Kim et al., 2002), it has been demonstrated that functional motor deficits associated with PD can be reduced after application of this new technology. Evidence shows that the underlying disease process does not destroy the transplanted fetal DA cells, although the patient's original DA system degeneration progresses (Piccini et al., 1999, 2000). The optimal DA cell regeneration system would reconstitute a normal network capable of restoring feedback-controlled release of DA in the nigro-striatal system (Bjorklund & Isacson, 2002). The success of cell therapy for neurological diseases is limited by access to preparation and development of highly specialized dopaminergic neurons found in the A9 and A10 region of the substantia nigra (SN) in the ventral mesencephalon, as well as technical and surgical steps associated with transplantation.

Type
Chapter
Information
Neurodegenerative Diseases
Neurobiology, Pathogenesis and Therapeutics
 , pp. 363 - 380
Publisher: Cambridge University Press
Print publication year: 2005

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