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Title: VEGF delivery with retrogradely transported lentivector prolongs survival in a mouse ALS model
Authors: Azzouz, Mimoun ×
Ralph, G Scott
Storkebaum, Erik
Walmsley, Lucy E
Mitrophanous, Kyriacos A
Kingsman, Susan M
Carmeliet, Peter
Mazarakis, Nicholas D #
Issue Date: May-2004
Publisher: Nature Publishing Group
Series Title: Nature vol:429 issue:6990 pages:413-7
Abstract: Amyotrophic lateral sclerosis (ALS) causes adult-onset, progressive motor neuron degeneration in the brain and spinal cord, resulting in paralysis and death three to five years after onset in most patients. ALS is still incurable, in part because its complex aetiology remains insufficiently understood. Recent reports have indicated that reduced levels of vascular endothelial growth factor (VEGF), which is essential in angiogenesis and has also been implicated in neuroprotection, predispose mice and humans to ALS. However, the therapeutic potential of VEGF for the treatment of ALS has not previously been assessed. Here we report that a single injection of a VEGF-expressing lentiviral vector into various muscles delayed onset and slowed progression of ALS in mice engineered to overexpress the gene coding for the mutated G93A form of the superoxide dismutase-1 (SOD1(G93A)) (refs 7-10), even when treatment was only initiated at the onset of paralysis. VEGF treatment increased the life expectancy of ALS mice by 30 per cent without causing toxic side effects, thereby achieving one of the most effective therapies reported in the field so far.
URI: 
ISSN: 0028-0836
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular and Vascular Biology
Laboratory of Behavioral and Developmental Genetics
Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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