This study characterizes motor function responses after early dosing of AVXS-101 (onasemnogene abeparvovec) in gene replacement therapy in infants with severe spinal muscular atrophy type 1 (SMA1).
The main effects of group, time-phase, and test condition on the ERD areas (%) were significant for the three brain areas, except the main effect of group in the SMA (Cz) and CH (C4) brain area.
We investigated the expression of myelin basic protein (MBP) and NG2, which are OL lineage markers, using SMNΔ7 mice (mSmn, SMN2, SMNΔ7) and cell cultures derived from induced pluripotent stem cells generated from SMA patients.
An English-language literature search of PubMed and MEDLINE (1946 to June 2018) was performed using the terms nusinersen, ISIS-SMN (Rx), and spinal muscular atrophy.
In this study, a novel compound was identified that increased SMN protein levels in vivo and ameliorated the disease phenotype in severe and intermediate mouse models of SMA.
The combined treatment of SMA cells with sub-optimal doses of LBH589 and of an antisense oligonucleotide that mimic Nusinersen (ASO_ISSN1) elicits additive effects on SMN2 splicing and SMN protein expression.
Spinal muscular atrophy (SMA) is caused by a homozygous deletion of the survival motor neuron 1 (SMN1) gene on chromosome 5, or a heterozygous deletion in combination with a point mutation in the second SMN1 allele.
An English-language literature search of PubMed and MEDLINE (1946 to June 2018) was performed using the terms nusinersen, ISIS-SMN (Rx), and spinal muscular atrophy.
We report here the finding of abnormal Golgi apparatus morphology in motor neuron like cells depleted of SMN as well as Golgi apparatus morphology in SMA patient fibroblasts.
Spinal muscular atrophy (SMA) is a recessive disorder caused by a mutation in the survival motor neuron 1 gene (SMN1); it affects 1 in 11 000 newborn infants.
The primary objective of the present study was to evaluate the applicability of the dosage of SMN gene produts in blood, as biomarker for SMA, and the safety of oral salbutamol, a beta2-adrenergic agonist modulating <i>SMN2</i> levels.
Risdiplam (RG7916, RO7034067) is an orally administered, centrally and peripherally distributed, survival of motor neuron 2 (SMN2) mRNA splicing modifier for the treatment of spinal muscular atrophy (SMA).
This review focuses on the advent of SMA gene therapy and summarizes different preclinical studies that were conducted leading up to the AAV9-SMA trial in SMA patients.
In this chapter, we describe the techniques used for in vitro screening and analysing in vivo biodistribution of CPP-conjugated ASOs targeting the survival motor neuron 2, SMN2, the dose-dependent modifying gene for SMA.
Moreover, the finding of similar nuclear reorganization in both atrophic and hypetrophic myofibers provides additional support that the SMN deficiency in SMA patients may primarily affect the skeletal myofibers.