Dataset Information
?CAR IGF-1 vector targeting of motor neurons ameliorates disease progression in ALS mice.
Ontology highlight
ABSTRACT: Objective
We have previously described the generation of coxsackievirus and adenovirus receptor (? CAR)-targeted vector, and shown that intramuscular delivery in mouse leg muscles resulted in specific retrograde transduction of lumbar-motor neurons (MNs). Here, we utilized the ? CAR-targeted vector to investigate the in vivo neuroprotective effects of lentivirally expressed IGF-1 for inducing neuronal survival and ameliorating the neuropathology and behavioral phenotypes of the SOD1G93A mouse model of ALS.Methods
We produced cell factories of IGF-1 expressing lentiviral vectors (LVs) bearing ? CAR or Vesicular Stomatitis Virus glycoprotein (VSV-G) on their surface so as to compare neuroprotection from MN transduced versus muscle transduced cells. We performed intramuscular delivery of either ? CAR IGF-1 or VSVG IGF-1 LVs into key muscles of SOD1G93A mice prior to disease onset at day 28. Motor performance, coordination and gait analysis were assessed weekly.Results
We observed substantial therapeutic efficacy only with the ? CAR IGF-1 LV pretreatment with up to 50% extension of survival compared to controls. ? CAR IGF-1 LV-treated animals retained muscle tone and had better motor performance during their prolonged survival. Histological analysis of spinal cord samples at end-stage further confirmed that ? CAR IGF-1 LV treatment delays disease onset by increasing MN survival compared with age-matched controls. Intrastriatal injection of ? CAR eGFP LV in rats leads to transduction of neurons and glia locally and neurons in olfactory bulb distally.Interpretation
Our data are indicative of the efficacy of the ? CAR IGF-1 LV in this model and support its candidacy for early noninvasive neuroprotective therapy in ALS.
SUBMITTER: Eleftheriadou I
PROVIDER: S-EPMC5048386 | biostudies-literature | 2016 Oct
REPOSITORIES: biostudies-literature
Publications
<i>α</i>CAR IGF-1 vector targeting of motor neurons ameliorates disease progression in ALS mice.
Annals of clinical and translational neurology 20160907 10
<h4>Objective</h4>We have previously described the generation of coxsackievirus and adenovirus receptor (<i>α</i> CAR)-targeted vector, and shown that intramuscular delivery in mouse leg muscles resulted in specific retrograde transduction of lumbar-motor neurons (MNs). Here, we utilized the <i>α</i> CAR-targeted vector to investigate the in vivo neuroprotective effects of lentivirally expressed <i>IGF-1</i> for inducing neuronal survival and ameliorating the neuropathology and behavioral phenot ...[more]
