Discovery Medicine, Volume 12, Number 65, Pages 291-305, october 2011 Abstract: Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder that causes degeneration of α-motor neurons. Frequently, muscle weakness is very severe causing affected infants to die before reaching two years of age, but mild forms of the disease can be characterized by relatively static muscle weakness for ma...

Spinal muscular atrophy (SMA) is caused by homozygous loss of the survival motor neuron (SMN1) gene. In virtually all SMA patients, a nearly identical copy gene is present, SMN2. SMN2 cannot fully compensate for the loss of SMN1 because the majority of transcripts derived from SMN2 lack a critical exon (exon 7), resulting in a dysfunctional SMN protein. Therefore, the critical distinction betwe...

Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disorder and a leading genetic cause of infantile mortality. SMA is caused by mutation or deletion of Survival Motor Neuron-1 (SMN1). The clinical features of the disease are caused by specific degeneration of alpha-motor neurons in the spinal cord, leading to muscle weakness, atrophy and, in the majority of cases, premat...

Spinal muscular atrophy (SMA) is a debilitating neuromuscular disease caused by the loss of survival of motor neuron (SMN) protein. Previously, we demonstrated that ISIS 396443, an antisense oligonucleotide (ASO) targeted to the SMN2 pre-mRNA, is a potent inducer of SMN2 exon 7 inclusion and SMN protein expression, and improves function and survival of mild and severe SMA mouse models. Here, we...

Spinal muscular atrophy (SMA) is caused by homozygous survival of motor neurons 1 (SMN1) gene deletions, leaving a duplicate gene, SMN2, as the sole source of SMN protein. However, most of the mRNA produced from SMN2 pre-mRNA is exon 7-skipped ( approximately 80%), resulting in a highly unstable and almost undetectable protein (SMNDelta7). We show that this splicing defect creates a potent degr...

Significant strides have been made during the past decade in the understanding of the molecular mechanisms that lead to the autosomal recessive motor neuron disease spinal muscular atrophy. Genetic studies revealed that spinal muscular atrophy is caused by mutation of the telomeric copy of the survival motor neuron gene ( SMN1), with all patients retaining at least one copy of the centromeric f...

INTRODUCTION Proximal spinal muscular atrophy (SMA) is a common autosomal recessively inherited neuromuscular disorder. It is caused by homozygous absence of the survival motor neuron 1 (SMN1) gene. SMN2, which modulates the severity of the disease, represents a major target for therapy. The aim of this study was to investigate whether SMN2 expression can be increased by caffeic acid, chlorogen...

Humans have two near identical copies of Survival Motor Neuron gene: SMN1 and SMN2. Loss of SMN1 coupled with the predominant skipping of SMN2 exon 7 causes spinal muscular atrophy (SMA), a neurodegenerative disease. SMA patient cells devoid of SMN1 provide a powerful system to examine splicing pattern of various SMN2 exons. Until now, similar system to examine splicing of SMN1 exons was unavai...

SMN1 and SMN2 (survival motor neuron) encode identical proteins. A critical question is why only the homozygous loss of SMN1, and not SMN2, results in spinal muscular atrophy (SMA). Analysis of transcripts from SMN1/SMN2 hybrid genes and a new SMN1 mutation showed a direct relationship between presence of disease and exon 7 skipping. We have reported previously that the exon-skipped product SMN...

BACKGROUND Spinal muscular atrophy (SMA) is a common neuromuscular disorder caused by mutations in SMN1. More than 95% of SMA patients carry homozygous SMN1 deletions. Thus, the SMN1 deletion test should be performed initially as part of the diagnostic process. However, SMN2, a highly homologous gene, hampers detection of SMN1 deletion. To differentiate between SMN1 and SMN2, many analysis meth...