title: Intramuscular administration of a VEGF zinc finger transcription factor activator (VEGF-ZFP-TF) improves functional outcomes in SOD1 rats.
abstract: Amyotrophic lateral sclerosis (ALS) is characterized by motor neuron loss leading to paralysis and death. Vascular endothelial growth factor (VEGF) has angiogenic, neurotrophic, and neuroprotective properties, and has preserved neuromuscular function and protected motor neurons in rats engineered to overexpress the human gene coding the mutated G93A form of the superoxide dismutase-1 (SOD1). We assessed the effects of intramuscular administration of a plasmid that encodes a zinc finger protein transcription factor (ZFP-TF) engineered to induce VEGF expression in the SOD1 rat model of ALS. Weekly injections of the plasmid preserved ipsilateral hindlimb grip strength and markedly improved rotarod performance in SOD1 rats compared to the vehicle-treated group. The number of motor neurons and the proportion of innervated neuromuscular junctions were similar in both groups. In conclusion, our data suggest that administration of the VEGF-ZFP-TF may be neuroprotective and has potential as a safe and practical approach for the management of motor disability in ALS.
authors.affiliation: Department of Neurosurgery , Emory University, Atlanta , Georgia, USA.
authors.forename: Michele A
authors.initials: MA
authors.lastname: Kliem
authors.forename: Brenten L
authors.initials: BL
authors.lastname: Heeke
authors.forename: Colin K
authors.initials: CK
authors.lastname: Franz
authors.forename: Igor
authors.initials: I
authors.lastname: Radovitskiy
authors.forename: Bethwel
authors.initials: B
authors.lastname: Raore
authors.forename: Emily
authors.initials: E
authors.lastname: Barrow
authors.forename: Brooke R
authors.initials: BR
authors.lastname: Snyder
authors.forename: Thais
authors.initials: T
authors.lastname: Federici
authors.forename: S
authors.initials: S
authors.lastname: Kaye Spratt
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Boulis
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D018482:Muscle, Skeletal / Q000502:physiology; D051381:Rats; D055647:Rats, Transgenic; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D000072105:Superoxide Dismutase-1; D014157:Transcription Factors / Q000008:administration & dosage* / Q000235:genetics / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000235:genetics / Q000502:physiology; D016335:Zinc Fingers / Q000235:genetics
chemical_list: C000606290:SOD1 protein, human; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1