Abstract:
:Spinal muscular atrophy (SMA) is a motor neuron disease caused by dysfunction of the survival motor neuron (SMN) gene. Human SMN gene is present in duplicated copies: SMN1 and SMN2. More than 95% of patients with SMA lack a functional SMN1 but retain at least one copy of SMN2. Unlike SMN1, SMN2 is primarily transcribed into truncated messenger RNA and produces low levels of SMN protein. We tested a therapeutic strategy by treating cultured lymphocytes from patients with SMA with hydroxyurea to modify SMN2 gene expression and to increase the production of SMN protein. Twenty lymphoblastoid cell lines (15 SMA and 5 control lines) were treated with hydroxyurea at 5 concentrations (0.5, 5, 50, 500, and 5,000 microg/ml) and 3 time points (24, 48, and 72 hours). SMN2 gene copy numbers were determined using real-time quantitative polymerase chain reaction. Hydroxyurea treatment resulted in a time-related and dose-dependent increase in the ratio of full-length to truncated SMN messenger RNA. SMN protein levels and intranuclear gems also were significantly increased in these hydroxyurea-treated cells. The SMN2 gene copy number correlated inversely with the SMA phenotypic severity. This study provides the first evidence for a therapeutic indication of hydroxyurea in SMA.
journal_name
Ann Neuroljournal_title
Annals of neurologyauthors
Grzeschik SM,Ganta M,Prior TW,Heavlin WD,Wang CHdoi
10.1002/ana.20548keywords:
subject
Has Abstractpub_date
2005-08-01 00:00:00pages
194-202issue
2eissn
0364-5134issn
1531-8249journal_volume
58pub_type
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journal_title:Annals of neurology
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journal_title:Annals of neurology
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更新日期:1987-06-01 00:00:00
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更新日期:1987-05-01 00:00:00
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pub_type: 杂志文章
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更新日期:2009-11-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.24199
更新日期:2014-08-01 00:00:00
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pub_type: 杂志文章
doi:10.1002/ana.410420609
更新日期:1997-12-01 00:00:00
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pub_type: 杂志文章
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更新日期:2001-07-01 00:00:00
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pub_type: 杂志文章
doi:10.1002/ana.21518
更新日期:2008-12-01 00:00:00
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更新日期:1986-05-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410370610
更新日期:1995-06-01 00:00:00
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journal_title:Annals of neurology
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doi:
更新日期:2000-05-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
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更新日期:2014-08-01 00:00:00
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pub_type: 杂志文章
doi:10.1002/ana.410230407
更新日期:1988-04-01 00:00:00
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更新日期:2020-09-01 00:00:00
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pub_type: 杂志文章,随机对照试验
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更新日期:2019-10-01 00:00:00
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更新日期:2003-12-01 00:00:00
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更新日期:1990-11-01 00:00:00
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journal_title:Annals of neurology
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更新日期:1984-12-01 00:00:00
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更新日期:2005-05-01 00:00:00