|
Spinal Muscular Atrophy
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
ZPR1 overexpression in vivo results in a systemic increase of SMN levels and rescues severe to moderate disease in SMA mice.
|
31828288 |
2020 |
|
Spinal Muscular Atrophy
|
0.100 |
Biomarker
|
disease |
BEFREE |
This is an orthologue of the stasimon/tmem41b gene, a downstream target of SMN, the depleted protein in spinal muscular atrophy (SMA), which partially recapitulates the SMA phenotype in fly and zebrafish models when mutated.
|
31797327 |
2020 |
|
Spinal Muscular Atrophy
|
0.100 |
Biomarker
|
disease |
BEFREE |
SMN deficiency causes neurodegenerative disease spinal muscular atrophy (SMA).
|
31799625 |
2020 |
|
Spinal Muscular Atrophy
|
0.100 |
Biomarker
|
disease |
BEFREE |
Then, to implement the fetal gene therapy, mouse fetuses received a single i.c.v. injection of a single-stranded (ss) or self-complementary (sc) AAV9-SMN vector that led to a lifespan of 93 (median of 63) or 171 (median 105) days for SMA mice.
|
31543414 |
2019 |
|
Spinal Muscular Atrophy
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Recently, these features were harnessed in a clinical trial conducted by AveXis in SMA patients, where AAV9 was employed as a vehicle for one-time administration of the SMN gene, the causative gene in SMA.
|
31243392 |
2019 |
|
Spinal Muscular Atrophy
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
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.
|
30733501 |
2019 |
|
Spinal Muscular Atrophy
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
The results provide direct evidence that SMA-related locomotor decline can be reproduced in the fly and support the use of patient-derived SMN missense mutations as a comprehensive system for modeling SMA.
|
31156382 |
2019 |
|
Spinal Muscular Atrophy
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
We investigated the presence of non-neuromuscular phenotypes in patients affected by Spinal Muscular Atrophy (SMA), a disorder caused by a mutation in the Survival of Motor Neuron (SMN) gene, and whether these phenotypes may be clinically detectable prior to clinical signs of neuromuscular degeneration and therefore independent of muscle weakness.
|
30870495 |
2019 |
|
Spinal Muscular Atrophy
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Primary hits were further evaluated for their ability to correct the splicing defect and resultant increase of SMN activity in SMA patient-derived fibroblasts.
|
31563042 |
2019 |
|
Spinal Muscular Atrophy
|
0.100 |
Biomarker
|
disease |
BEFREE |
Thus, severe brain involvement may likely be the full end manifestation of an already extreme SMA phenotype caused by substantial reduction of the SMN protein in the brain.ANN NEUROL 2019;86:458-462.
|
31301241 |
2019 |
|
Spinal Muscular Atrophy
|
0.100 |
Biomarker
|
disease |
BEFREE |
In vitro experiments showed that calpain activation induces SMN cleavage in CD1 and SMA mouse spinal cord MNs.
|
30327977 |
2019 |
|
Spinal Muscular Atrophy
|
0.100 |
Biomarker
|
disease |
BEFREE |
Onasemnogene abeparvovec (onasemnogene abeparvovec-xioi; formerly AVXS-101; ZOLGENSMA<sup>®</sup>) is an adeno-associated viral vector-based gene therapy designed to deliver a functional copy of the human survival motor neuron (SMN) gene to the motor neuron cells of patients with spinal muscular atrophy (SMA).
|
31270752 |
2019 |
|
Spinal Muscular Atrophy
|
0.100 |
Biomarker
|
disease |
BEFREE |
Reduced expression of the survival motor neuron (SMN) protein causes the neurodegenerative disease spinal muscular atrophy (SMA).
|
31851921 |
2019 |
|
Spinal Muscular Atrophy
|
0.100 |
Biomarker
|
disease |
BEFREE |
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.
|
30408476 |
2019 |
|
Spinal Muscular Atrophy
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Reduced SMN protein levels in SMA patients lead to progressive degeneration of spinal motor neurons (MNs).
|
30667343 |
2019 |
|
Spinal Muscular Atrophy
|
0.100 |
Biomarker
|
disease |
BEFREE |
SMN deficiency causes pain hypersensitivity in a mild SMA mouse model through enhancing excitability of nociceptive dorsal root ganglion neurons.
|
31019235 |
2019 |
|
Spinal Muscular Atrophy
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
On the other hand, levetiracetam did not affect the expression level of SMN protein in SMA-iPSCs-MNs.
|
31102025 |
2019 |
|
Spinal Muscular Atrophy
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Lentiviral-mediated transgenic expression of SMN where the dilysine domain in exon 2b was mutated was not able to rescue the SMA phenotype despite robust expression of the mutant SMN protein in brain, muscle and spinal cord.
|
31060774 |
2019 |
|
Spinal Muscular Atrophy
|
0.100 |
Biomarker
|
disease |
BEFREE |
Spinal muscular atrophy (SMA) is a health- and life-limiting neuromuscular disorder caused by a deficiency in survival motor neuron (SMN) protein.
|
31361024 |
2019 |
|
Spinal Muscular Atrophy
|
0.100 |
Biomarker
|
disease |
BEFREE |
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.
|
30008228 |
2019 |
|
Spinal Muscular Atrophy
|
0.100 |
Biomarker
|
disease |
BEFREE |
Recently, nusinersen, an antisense oligonucleotide (ASO) that corrects SMN2 splicing and thereby increases full-length SMN protein, has been approved by the FDA and EMA for SMA therapy.
|
31230718 |
2019 |
|
Spinal Muscular Atrophy
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
SYNCRIP overexpression rescued spinal muscular atrophy motor neurons, due to the subsequent increase in SMN and their downstream target NRXN2 through a positive loop mechanism and ameliorated SMN-loss-related pathological phenotypes in Caenorhabditis elegans and mouse models.
|
30649277 |
2019 |
|
Spinal Muscular Atrophy
|
0.100 |
Biomarker
|
disease |
BEFREE |
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.
|
31183542 |
2019 |
|
Spinal Muscular Atrophy
|
0.100 |
Biomarker
|
disease |
BEFREE |
Overall, these data demonstrate that STMN1 can significantly reduce the SMA phenotype independent of restoring SMN protein and highlight the importance of developing SMN-independent therapeutics for the treatment of SMA.
|
31363739 |
2019 |
|
Spinal Muscular Atrophy
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
<b>Background:</b> 5q spinal muscular atrophy (SMA) is an autosomal recessive lower motoneuron disease caused by deletion or mutations in the survival motor neuron 1 gene (<i>SMN1</i>) which results in reduced expression of full-length SMN protein.
|
31736847 |
2019 |