Gene transfer techniques for the delivery of GDNF in Parkinson's disease
Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor disturbances caused by an alteration of the dopaminergic nigrostriatal system. Current symptomatic treatments for PD include dopaminergic drug administration, deep brain stimulation, ablative surgery and fetal cell transplantation. Though these approaches have significant beneficial effects, they are hampered by limiting side-effects, but more importantly they do not change the disease progression. Alternative restorative and neuroprotective strategies have therefore to be considered. Neuroprotective effects of neurotrophic factors, anti-apoptotic and antioxidant molecules are currently being investigated for this purpose. Among neurotrophic molecules, the potential of the glial cell line-derived neurotrophic factor (GDNF) to protect the nigral dopaminergic neurons and/or rescue striatal dopamine levels has been extensively documented. For GDNF to become a clinical reality, appropriate delivery techniques will have to be developed. This chapter focuses on the potential of encapsulated cells and viral vectors to locally release neurotrophic factors in experimental models of PD
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Discussion p. 215-219, 302-306 Author address: Division of Surgical Research and Gene Therapy Center, Lausanne University Medical School, CHUV, CH-1011 Lausanne, Switzerland
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