2019
DOI: 10.1093/hmg/ddz142
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AAV9-mediated delivery of miR-23a reduces disease severity in Smn2B/−SMA model mice

Abstract: Spinal muscular atrophy (SMA) is a neuromuscular disease caused by deletions or mutations in survival motor neuron 1 (SMN1). The molecular mechanisms underlying motor neuron degeneration in SMA remain elusive, as global cellular dysfunction obscures the identification and characterization of disease-relevant pathways and potential therapeutic targets. Recent reports have implicated microRNA (miRNA) dysregulation as a potential contributor to the pathological mechanism in SMA. To characterize miRNAs that are di… Show more

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Cited by 31 publications
(24 citation statements)
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“…miR-2 binds and inhibits gar-2 mRNA translation, but does not reduce transcript levels; and gar-2 loss ameliorates smn-1 neuromuscular defects, suggesting that miR-2/miR-128 may ameliorate neuromuscular defects (O'Hern et al, 2017). In SMA patients and mice, miR-23a significantly reduces the pathology in SMA mice, including increased motor neuron size, reduced neuromuscular junction pathology, increased muscle fiber area, and extended survival (Kaifer et al, 2019). miR-206 reduces the severity of SMA pathology, slowing down disease progression, improving behavioral performance and increasing survival rate of mice.…”
Section: Mirnas That Attenuate Muscle Atrophymentioning
confidence: 99%
“…miR-2 binds and inhibits gar-2 mRNA translation, but does not reduce transcript levels; and gar-2 loss ameliorates smn-1 neuromuscular defects, suggesting that miR-2/miR-128 may ameliorate neuromuscular defects (O'Hern et al, 2017). In SMA patients and mice, miR-23a significantly reduces the pathology in SMA mice, including increased motor neuron size, reduced neuromuscular junction pathology, increased muscle fiber area, and extended survival (Kaifer et al, 2019). miR-206 reduces the severity of SMA pathology, slowing down disease progression, improving behavioral performance and increasing survival rate of mice.…”
Section: Mirnas That Attenuate Muscle Atrophymentioning
confidence: 99%
“…Excitingly, a very recent study showed that injection of a self-complementary AAV9 viral vector to reintroduce miR-23a into the Smn 2B/– SMA mouse model could increase MN size, reduce NMJ pathology, and extend survival. 106 The detailed mechanisms underlying how miR-23a -mediated target pathways lead to SMA pathology have yet to be characterized. However, these findings suggest that a specific cohort of miRNAs might cause MN vulnerability in SMA, and identification of those miRNA culprits and their targets could provide a new treatment strategy for SMA.…”
Section: Therapeutic Potentials Of Mirna For Smamentioning
confidence: 99%
“…It remains under debate if dysregulated miRNAs and the corresponding miRNA-mediated target responses are cell-context dependent (i.e., specifically in MNs or in all neurons of the spinal cord), given that SMN is expressed ubiquitously and compromised expression of SMN may selectively affect miRNA homeostasis in different tissues (Magri et al, 2018). In this regard, a very recent study aimed to identify miRNAs that are differentially regulated in SMA from iPSC-derived MNs (Kaifer et al, 2019). In that study, Kaifer et al only identified a subset of 16 miRNAs whose expression is significantly reduced more than 2-fold in SMA MNs when compared to control MNs.…”
Section: Micrornas During Motor Neuron Degeneration In Smamentioning
confidence: 99%