Title: Treatment of motoneuron degeneration by intracerebroventricular delivery of VEGF in a rat model of ALS
Authors: Storkebaum, Erik *
Lambrechts, Diether *
Dewerchin, Mieke
Moreno-Murciano, Maria-Paz
Appelmans, Saskia
Oh, Hideyasu
Van Damme, Philip
Rutten, Bart
Man, Wing Yan
De Mol, Maria
Wyns, Sabine
Manka, David
Vermeulen, Kristel
Van Den Bosch, Ludo
Mertens, Nico
Schmitz, Christoph
Robberecht, Wim
Conway, Edward
Collen, Desire
Moons, Lieve
Carmeliet, Peter # ×
Issue Date: Jan-2005
Publisher: Nature America Inc.
Series Title: Nature Neuroscience vol:8 issue:1 pages:85-92
Abstract: Neurotrophin treatment has so far failed to prolong the survival of individuals affected with amyotrophic lateral sclerosis (ALS), an incurable motoneuron degenerative disorder. Here we show that intracerebroventricular (i.c.v.) delivery of recombinant vascular endothelial growth factor (Vegf) in a SOD1(G93A) rat model of ALS delays onset of paralysis by 17 d, improves motor performance and prolongs survival by 22 d, representing the largest effects in animal models of ALS achieved by protein delivery. By protecting cervical motoneurons, i.c.v. delivery of Vegf is particularly effective in rats with the most severe form of ALS with forelimb onset. Vegf has direct neuroprotective effects on motoneurons in vivo, because neuronal expression of a transgene expressing the Vegf receptor prolongs the survival of SOD1(G93A) mice. On i.c.v. delivery, Vegf is anterogradely transported and preserves neuromuscular junctions in SOD1(G93A) rats. Our findings in preclinical rodent models of ALS may have implications for treatment of neurodegenerative disease in general.
ISSN: 1097-6256
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular and Vascular Biology
Vesalius Research Centre (-)
Research Group Experimental Neurology
Animal Physiology and Neurobiology Section - miscellaneous
Laboratory for Neurobiology (Vesalius Research Center)
Laboratory of Translational Genetics (Vesalius Research Center) (+)
Laboratory of Angiogenesis and Vascular Metabolism (VIB-KU Leuven Centre for Cancer Biology) (+)
* (joint) first author
× corresponding author
# (joint) last author

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