Journal of the neurological sciences · 2007
The effect of hydroxyurea in spinal muscular atrophy cells and patients.
СтатьяРандомизированное исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Liang Wen-Chen, Yuo Chung-Yee, Chang Jan-Gowth, Chen Yi-Ching, Chang Yung-Fu, Wang Hui-Yi, Ju Yun-Huei, Chiou Shyh-Shin, Jong Yuh-Jyh
Аннотация
BACKGROUND: Spinal muscular atrophy (SMA) is a degenerative motor neuron disease caused by homozygous mutations of the survival motor neuron 1 (SMN1) gene. Effective treatment for SMA is unavailable at present. The aim of this study was to investigate the effect of hydroxyurea (HU) in SMA cells and patients.
MATERIALS AND METHODS: Fifteen SMA lymphoid and three fibroblast cell lines, 2 from SMA patients and 1 control, were treated with HU at different concentrations, and 33 patients (types II, III) randomized into three groups on different HU dosage, 20, 30, 40 mg/kg/day, were treated for 8 weeks and followed up for another drug-free 8 weeks. The effect of HU on SMN2 gene expression and clinical manifestations was evaluated.
RESULTS: After treatment, in vitro, full-length mRNA level and gems number increased significantly, and hnRNP A1 protein decreased. In vivo, there were slight increases in muscle strength scores at 4 weeks and full-length SMN mRNA at 8 weeks in 30 mg/kg/day subgroup.
CONCLUSIONS: Treating with HU enhanced SMN2 gene expression in SMA cells and showed slight trend towards improvement in some clinical outcome measures in SMA patients which suggests HU may be safe to use in SMA patients but larger randomized, placebo-controlled, double-blind trials are needed to further investigate its efficacy.
MATERIALS AND METHODS: Fifteen SMA lymphoid and three fibroblast cell lines, 2 from SMA patients and 1 control, were treated with HU at different concentrations, and 33 patients (types II, III) randomized into three groups on different HU dosage, 20, 30, 40 mg/kg/day, were treated for 8 weeks and followed up for another drug-free 8 weeks. The effect of HU on SMN2 gene expression and clinical manifestations was evaluated.
RESULTS: After treatment, in vitro, full-length mRNA level and gems number increased significantly, and hnRNP A1 protein decreased. In vivo, there were slight increases in muscle strength scores at 4 weeks and full-length SMN mRNA at 8 weeks in 30 mg/kg/day subgroup.
CONCLUSIONS: Treating with HU enhanced SMN2 gene expression in SMA cells and showed slight trend towards improvement in some clinical outcome measures in SMA patients which suggests HU may be safe to use in SMA patients but larger randomized, placebo-controlled, double-blind trials are needed to further investigate its efficacy.
Предметные рубрики MeSH
AdolescentAdultCells, CulturedChildChild, PreschoolCyclic AMP Response Element-Binding ProteinDose-Response Relationship, DrugFemaleFibroblastsFollow-Up StudiesGene Expression RegulationHand StrengthHeterogeneous Nuclear Ribonucleoprotein A1Heterogeneous-Nuclear Ribonucleoprotein Group A-BHumansHydroxyureaLymphocytesMaleMultivariate AnalysisMuscular Atrophy, SpinalNerve Tissue ProteinsNucleic Acid Synthesis InhibitorsRNA-Binding ProteinsSMN Complex ProteinsSurvival of Motor Neuron 1 ProteinSurvival of Motor Neuron 2 Protein