Combinatorial treatment for spinal muscular atrophy

Spinal muscular atrophy (SMA) is a motoneuron disease caused by the loss of the geneSMN1, encoding a protein essential for motoneuron survival. Additional copies of an alternateSMN gene,SMN2, are present in the genome, but exon 7 is skipped in SMN2 mRNA producing an unstable protein (SMN Δ7). Therapeutic approaches for SMA include (1) viral‐mediated replacement ofSMN1, (2) antisense oligonucleotide (ASO) or small molecule mediated correction SMN2 splicing, and (3) increasedSMN2 expression induced by histone deacetylase (HDAC) inhibitors. This Editorial highlights this study by Pagliarni et al. in which they used combined treatment of cell models of SMA with an ASO and an orally delivered HDAC inhibitor (panobinostat) to overcome the limitations of a single ‐therapeutic approach. AbstractSpinal muscular atrophy (SMA) is a severe autosomal recessive motor neuron disease caused by the loss ofSMN1, which encodes a protein essential for motor neuron survival. SMA patients have one or more copies of an alternateSMN gene,SMN2, which is nearly identical toSMN1.SMN2 differs at a single nucleotide fromSMN1 which results in the skipping of exon 7 in the mRNA and produces an unstable protein (SMN Δ7). Therapeutic approaches that have been undertaken include (1) replacement ofSMN1 by gene delivery mediated by adeno ‐associated virus serotype 9 (AAV9) (Zolgensma), (2) correction of the aberrantSMN2 splicing using an antisense oligonucleotide (ASO) or small molecule (nusinersin, ris...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: EDITORIAL HIGHLIGHT Source Type: research