Emerging treatment options for spinal muscular atrophy

被引：0
作者：
Barrington G. Burnett
Thomas O. Crawford
Charlotte J. Sumner
机构：
来源：
Current Treatment Options in Neurology | 2009年 / 11卷
关键词：
Spinal Muscular Atrophy; Riluzole; Survival Motor Neuron; SMN2 Gene; Spinal Muscular Atrophy Type;
D O I：
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摘要：
The motor neuron disease spinal muscular atrophy (SMA) is one of the leading genetic killers of infants worldwide. SMA is caused by mutation of the survival motor neuron 1 (SMN1) gene and deficiency of the survival motor neuron (SMN) protein. All patients retain one or more copies of the SMN2 gene, which (by producing a small amount of the SMN protein) rescues embryonic lethality and modifies disease severity. Rapid progress continues in dissecting the cellular functions of the SMN protein, but the mechanisms linking SMN deficiency with dysfunction and loss of functioning motor units remain poorly defined. Clinically, SMA should to be distinguished from other neuromuscular disorders, and the diagnosis can be readily confirmed with genetic testing. Quality of life and survival of SMA patients are improved with aggressive supportive care including optimized respiratory and nutritional care and management of scoliosis and contractures. Because SMA is caused by inadequate amounts of SMN protein, one aim of current SMA therapeutics development is to increase SMN protein levels in SMA patients by activating SMN2 gene expression and/or increasing levels of full-length SMN2 transcripts. Several potential therapeutic compounds are currently being studied in clinical trials in SMA patients.
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页码：90 / 101
页数：11
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  • [1] Lefebvre S.(1995)Identification and characterization of a spinal muscular atrophy-determining gene Cell 80 155-165
  • [2] Burglen L.(1999)A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy Proc Natl Acad Sci U S A 96 6307-6311
  • [3] Reboullet S.(1999)A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2 Hum Mol Genet 8 1177-1183
  • [4] Lorson C.L.(2005)SMNDelta7, the major product of the centromeric survival motor neuron (SMN2) gene, extends survival in mice with spinal muscular atrophy and associates with full-length SMN Hum Mol Genet 14 845-857
  • [5] Hahnen E.(1998)SMN oligomerization defect correlates with spinal muscular atrophy severity Nat Genet 19 63-66
  • [6] Androphy E.J.(1998)A novel function for SMN, the spinal muscular atrophy disease gene product, in pre-mRNA splicing Cell 95 615-624
  • [7] Wirth B.(2005)Molecular and functional analysis of intragenic SMN1 mutations in patients with spinal muscular atrophy Hum Mutat 25 64-71
  • [8] Monani U.R.(2002)Quantitative analyses of SMN1 and SMN2 based on real-time lightCycler PCR: fast and highly reliable carrier testing and prediction of severity of spinal muscular atrophy Am J Hum Genet 70 358-368
  • [9] Lorson C.L.(2008)Plastin 3 is a protective modifier of autosomal recessive spinal muscular atrophy Science 320 524-527
  • [10] Parsons D.W.(1999)The Caenorhabditis elegans orthologue of the human gene responsible for spinal muscular atrophy is a maternal product critical for germline maturation and embryonic viability Hum Mol Genet 8 2133-2143
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