| pubmed-article:20624852 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:20624852 | lifeskim:mentions | umls-concept:C0026847 | lld:lifeskim |
| pubmed-article:20624852 | lifeskim:mentions | umls-concept:C0332307 | lld:lifeskim |
| pubmed-article:20624852 | lifeskim:mentions | umls-concept:C0025914 | lld:lifeskim |
| pubmed-article:20624852 | lifeskim:mentions | umls-concept:C0026809 | lld:lifeskim |
| pubmed-article:20624852 | lifeskim:mentions | umls-concept:C0026336 | lld:lifeskim |
| pubmed-article:20624852 | lifeskim:mentions | umls-concept:C1367790 | lld:lifeskim |
| pubmed-article:20624852 | lifeskim:mentions | umls-concept:C0927232 | lld:lifeskim |
| pubmed-article:20624852 | lifeskim:mentions | umls-concept:C0027540 | lld:lifeskim |
| pubmed-article:20624852 | lifeskim:mentions | umls-concept:C0035687 | lld:lifeskim |
| pubmed-article:20624852 | lifeskim:mentions | umls-concept:C1420258 | lld:lifeskim |
| pubmed-article:20624852 | lifeskim:mentions | umls-concept:C1947976 | lld:lifeskim |
| pubmed-article:20624852 | pubmed:issue | 15 | lld:pubmed |
| pubmed-article:20624852 | pubmed:dateCreated | 2010-8-3 | lld:pubmed |
| pubmed-article:20624852 | pubmed:abstractText | Increasing survival of motor neuron 2, centromeric (SMN2) exon 7 inclusion to express more full-length SMN protein in motor neurons is a promising approach to treat spinal muscular atrophy (SMA), a genetic neurodegenerative disease. Previously, we identified a potent 2'-O-(2-methoxyethyl) (MOE) phosphorothioate-modified antisense oligonucleotide (ASO) that blocks an SMN2 intronic splicing silencer element and efficiently promotes exon 7 inclusion in transgenic mouse peripheral tissues after systemic administration. Here we address its efficacy in the spinal cord--a prerequisite for disease treatment--and its ability to rescue a mild SMA mouse model that develops tail and ear necrosis, resembling the distal tissue necrosis reported in some SMA infants. Using a micro-osmotic pump, we directly infused the ASO into a lateral cerebral ventricle in adult mice expressing a human SMN2 transgene; the ASO gave a robust and long-lasting increase in SMN2 exon 7 inclusion measured at both the mRNA and protein levels in spinal cord motor neurons. A single embryonic or neonatal intracerebroventricular ASO injection strikingly rescued the tail and ear necrosis in SMA mice. We conclude that this MOE ASO is a promising drug candidate for SMA therapy, and, more generally, that ASOs can be used to efficiently redirect alternative splicing of target genes in the CNS. | lld:pubmed |
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| pubmed-article:20624852 | pubmed:language | eng | lld:pubmed |
| pubmed-article:20624852 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20624852 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:20624852 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20624852 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20624852 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20624852 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:20624852 | pubmed:month | Aug | lld:pubmed |
| pubmed-article:20624852 | pubmed:issn | 1549-5477 | lld:pubmed |
| pubmed-article:20624852 | pubmed:author | pubmed-author:KrainerAdrian... | lld:pubmed |
| pubmed-article:20624852 | pubmed:author | pubmed-author:BennettC... | lld:pubmed |
| pubmed-article:20624852 | pubmed:author | pubmed-author:HungGeneG | lld:pubmed |
| pubmed-article:20624852 | pubmed:author | pubmed-author:PassiniMarco... | lld:pubmed |
| pubmed-article:20624852 | pubmed:author | pubmed-author:HuaYiminY | lld:pubmed |
| pubmed-article:20624852 | pubmed:author | pubmed-author:RigoFrankF | lld:pubmed |
| pubmed-article:20624852 | pubmed:author | pubmed-author:SahashiKentar... | lld:pubmed |
| pubmed-article:20624852 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:20624852 | pubmed:day | 1 | lld:pubmed |
| pubmed-article:20624852 | pubmed:volume | 24 | lld:pubmed |
| pubmed-article:20624852 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:20624852 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:20624852 | pubmed:pagination | 1634-44 | lld:pubmed |
| pubmed-article:20624852 | pubmed:dateRevised | 2011-7-22 | lld:pubmed |
| pubmed-article:20624852 | pubmed:meshHeading | pubmed-meshheading:20624852... | lld:pubmed |
| pubmed-article:20624852 | pubmed:meshHeading | pubmed-meshheading:20624852... | lld:pubmed |
| pubmed-article:20624852 | pubmed:meshHeading | pubmed-meshheading:20624852... | lld:pubmed |
| pubmed-article:20624852 | pubmed:meshHeading | pubmed-meshheading:20624852... | lld:pubmed |
