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Mandatory Fields
Reviews
Kelly, MJ;O'Keeffe, GW;Sullivan, AM
2015
May
Viral vector delivery of neurotrophic factors for Parkinson's disease therapy
Validated
1
WOS: 29 ()
Optional Fields
MIDBRAIN DOPAMINERGIC-NEURONS CONVECTION-ENHANCED DELIVERY GROWTH/DIFFERENTIATION FACTOR 5 6-HYDROXYDOPAMINE IN-VIVO FACTOR IMPROVES SURVIVAL LESIONED RHESUS-MONKEYS FACTOR-BETA SUPERFAMILY CENTRAL-NERVOUS-SYSTEM MEDIATED GENE-TRANSFER RAT MODEL
Parkinson's disease (PD) is a neurodegenerative disorder characterised by the progressive loss of midbrain dopaminergic neurons, which causes motor impairments. Current treatments involve dopamine replacement to address the disease symptoms rather than its cause. Factors that promote the survival of dopaminergic neurons have been proposed as novel therapies for PD. Several dopaminergic neurotrophic factors (NTFs) have been examined for their ability to protect and/or restore degenerating dopaminergic neurons, both in animal models and in clinical trials. These include glial cell line-derived neurotrophic factor, neurturin, cerebral dopamine neurotrophic factor and growth/differentiation factor 5. Delivery of these NTFs via injection or infusion to the brain raises several practical problems. A new delivery approach for NTFs involves the use of recombinant viral vectors to enable long-term expression of these factors in brain cells. Vectors used include those based on adenoviruses, adeno-associated viruses and lentiviruses. Here we review progress to date on the potential of each of these four NTFs as novel therapeutic strategies for PD, as well as the challenges that have arisen, from pre-clinical analysis to clinical trials. We conclude by discussing recently-developed approaches to optimise the delivery of NTF-carrying viral vectors to the brain.
NEW YORK
CAMBRIDGE UNIV PRESS
1462-3994
10.1017/erm.2015.6
Grant Details