Neurogenetic and Muscular Disorders Research

Diminished motor neuron activity driven by abnormal astrocytic GLAST glutamate transporter activity in spinal muscular atrophy is not fully restored after lentiviral SMN delivery

This study identifies a non-cell autonomous mechanism in SMA where astrocytic GLAST dysfunction contributes to motor neuron dysfunction, which is partially restored by SMN re-expression.

Exon7 Targeted CRISPR-Prime Editing Approaches for SMN2 Gene Editing in Spinal Muscular Atrophy (SMA) Disease Can Increase In Vitro SMN Expression

This study uses CRISPR-Prime Editing to correct two point mutations in the SMN2 gene, increasing SMN expression in SMA-related cells.

Viral mediated knockdown of GATA6 in SMA iPSC-derived astrocytes prevents motor neuron loss and microglial activation

Central and peripheral delivery of AAV9-SMN target different pathomechanisms in a mouse model of spinal muscular atrophy

The paper compares IV and ICV delivery of AAV9-SMN in SMA mice, showing different SMN restoration patterns and treatment outcomes.

Systemic antibody-oligonucleotide delivery to the central nervous system ameliorates mouse models of spinal muscular atrophy

This study demonstrates that systemic delivery of ASO conjugated to a brain-targeting antibody improves SMN2 splicing and survival in SMA mouse models.

Assessment of CSF biomarkers and microRNA-mediated disease mechanisms in SMA

This study assesses CSF biomarkers and microRNA-mediated mechanisms in SMA patients treated with nusinersen, finding improved microRNA expression but persistent cellular stress and astrocyte dysfunction.

Short duration splice promoting compound enables a tunable mouse model of spinal muscular atrophy

The paper describes a splicing modifier compound that creates a tunable mouse model of spinal muscular atrophy, showing efficacy in preventing and reversing SMA phenotypes with short-term treatment.

SMN1 copy-number and sequence variant analysis from next generation sequencing data

SMAca is a tool to detect SMA carriers and estimate SMN1 copy-number from NGS data using variant-specific knowledge, validated on 326 samples.

LCM-seq reveals unique transcriptional adaption mechanisms of resistant neurons in spinal muscular atrophy

This study uses LCM-seq to analyze transcriptional changes in SMA, identifying cell-type specific adaptations that explain resistance in ocular motor neurons.

Intimate functional interactions between TGS1 and the Smn complex revealed by an analysis of the Drosophila eye development

This study identifies functional interactions between TGS1 and the Smn complex in Drosophila eye development, showing their roles in retinal progenitor cell viability and eye size.

A subset of SMN complex members have a specific role in tissue regeneration via ERBB pathway-mediated proliferation

The paper identifies gemin3 as a regeneration-essential gene in zebrafish and shows smn1, gemin3, and gemin5 inhibit the ErbB pathway to promote cell proliferation during tissue regeneration.

Loss of BICD2 in muscle drives motor neuron loss in a developmental form of spinal muscular atrophy

This study shows that loss of BICD2 in muscle drives motor neuron loss in SMALED2 through a non-cell autonomous mechanism involving impaired secretory pathways.

Spinal muscular atrophy diagnosis and carrier screening from whole-genome sequencing data

This paper develops a method to accurately determine SMN1 and SMN2 copy numbers from whole-genome sequencing data, enabling SMA diagnosis and carrier screening with high precision and recall.

Temperature sensitive SMA-causing point mutations lead to SMN instability, locomotor defects, and premature lethality in Drosophila

This paper shows that temperature-sensitive SMA-causing mutations in Drosophila SMN lead to SMN instability, locomotor defects, and premature death, highlighting SMN's role in development.

Combining multi-omics and drug perturbation profiles to identify novel treatments that improve disease phenotypes in spinal muscular atrophy

This study identifies novel drug treatments for spinal muscular atrophy by integrating multi-omics data and drug perturbation profiles, showing harmine improves disease phenotypes in models.

Comprehensive modeling of Spinal Muscular Atrophy in Drosophila melanogaster

This study models spinal muscular atrophy in Drosophila using patient-derived missense mutations, showing similar phenotypes to human SMA across multiple adult neuromuscular metrics.

Stasimon contributes to the loss of sensory synapses and motor neuron death in a mouse model of spinal muscular atrophy

This study shows that Stasimon overexpression in SMA mice improves motor function by preventing synaptic loss and motor neuron death through mechanisms involving p53 regulation.

SMN1 and SMN2 Copy Number Determination by droplet digital PCR (ddPCR) based on Extreme Value Theory for Threshold Estimation

This paper improves SMN1 and SMN2 copy number determination using ddPCR by applying extreme value theory for threshold estimation, achieving higher accuracy than QuantaSoft on challenging samples.

In vivo translatome profiling reveals early defects in ribosome biology underlying SMA pathogenesis

The paper identifies early translational defects in SMA mice, showing reduced translational efficiency and ribosome numbers in motor neurons, which are rescued by SMN restoration.