TY - JOUR
T1 - Viral vector-mediated gene therapy for Parkinson's disease
AU - Emborg, Marina E.
AU - Deglon, Nicole
AU - Leventhal, Liza
AU - Aebischer, Patrick
AU - Kordower, Jeffrey H.
N1 - Funding Information:
This work was supported by The Retirement Research Foundation (MEE), The Blowitz-Ridgeway Foundation (MEE) NIH RO1 NS40578-01 (MEE), Swiss National Science Foundation (PA), Swiss National Program in Neurological Diseases (PA), U.S. Department of Defense (JHK), and The Charles Shapiro Foundation (JHK).
PY - 2001/12
Y1 - 2001/12
N2 - Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects 1% of the population above the age of 60. The cause of the disease remains unknown. The histopathological hallmarks of the disease are intracytoplasmic Lewy bodies and dopaminergic striatal insufficiency secondary to a loss of dopaminergic neurons in the substantia nigra pars compacta (SN). Pharmacological treatment options for PD are often limited by the ability of prodopaminergic drugs to function within the nigrostriatal system, without activating other dopaminergic, but non-nigrostriatal regions, of the CNS. Even if this obstacle is overcome, considerations regarding the chronic availability of the drug can limit drug utility. Gene delivery systems are ideal for delivering therapeutic molecules to site specific regions of the CNS. Via gene therapy, a piece or pieces of DNA placed into a carrying vector encoding for a substance of interest is introduced into cells. While there are many ways to apply this technology, this review will focus on in vivo gene therapy as it applies to Parkinson's disease. Using stereotaxic surgery, vectors can be introduced into specific target areas in the brain and deliver genes encoding for therapeutic molecules. By delivering genes using gene therapy approaches, a therapeutic molecule can be delivered chronically in a site-specific fashion, diminishing unwanted side effects and repeated interventions to obtain useful levels of the drug. Throughout this review, we discuss the potential for gene delivery aimed at enhancing dopamine production or providing neuroprotection for nigrostriatal neurons to serve as a therapeutic strategy for PD.
AB - Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects 1% of the population above the age of 60. The cause of the disease remains unknown. The histopathological hallmarks of the disease are intracytoplasmic Lewy bodies and dopaminergic striatal insufficiency secondary to a loss of dopaminergic neurons in the substantia nigra pars compacta (SN). Pharmacological treatment options for PD are often limited by the ability of prodopaminergic drugs to function within the nigrostriatal system, without activating other dopaminergic, but non-nigrostriatal regions, of the CNS. Even if this obstacle is overcome, considerations regarding the chronic availability of the drug can limit drug utility. Gene delivery systems are ideal for delivering therapeutic molecules to site specific regions of the CNS. Via gene therapy, a piece or pieces of DNA placed into a carrying vector encoding for a substance of interest is introduced into cells. While there are many ways to apply this technology, this review will focus on in vivo gene therapy as it applies to Parkinson's disease. Using stereotaxic surgery, vectors can be introduced into specific target areas in the brain and deliver genes encoding for therapeutic molecules. By delivering genes using gene therapy approaches, a therapeutic molecule can be delivered chronically in a site-specific fashion, diminishing unwanted side effects and repeated interventions to obtain useful levels of the drug. Throughout this review, we discuss the potential for gene delivery aimed at enhancing dopamine production or providing neuroprotection for nigrostriatal neurons to serve as a therapeutic strategy for PD.
KW - Dopamine
KW - Gene therapy
KW - Glial cell derived neurotrophic factor
KW - Parkinson's disease
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U2 - 10.1016/S1566-2772(01)00027-5
DO - 10.1016/S1566-2772(01)00027-5
M3 - Review article
AN - SCOPUS:0347156579
SN - 1566-2772
VL - 1
SP - 496
EP - 506
JO - Clinical Neuroscience Research
JF - Clinical Neuroscience Research
IS - 6
ER -