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
Department of Pediatrics, Kaohsiung Medical University Hospital, Taiwan.
J Neurol Sci. 2008 May 15;268(1-2):87-94. doi: 10.1016/j.jns.2007.11.012. Epub 2007 Dec 31.
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.
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.
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.
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.
脊髓性肌萎缩症（SMA）是一种由生存运动神经元1（SMN1）基因纯合突变引起的退行性运动神经元疾病。目前尚无针对SMA的有效治疗方法。本研究旨在探讨羟基脲（HU）对SMA细胞和患者的影响。
用不同浓度的HU处理15种SMA淋巴细胞系和3种成纤维细胞系，其中2种来自SMA患者，1种为对照，另外将33例（II型、III型）患者随机分为三组，分别给予不同剂量的HU，即20、30、40mg/kg/天，治疗8周，并在停药后随访8周。评估HU对SMN2基因表达和临床表现的影响。
治疗后，在体外，全长mRNA水平和宝石数量显著增加，hnRNP A1蛋白减少。在体内，30mg/kg/天亚组在4周时肌肉力量评分略有增加，在8周时全长SMN mRNA略有增加。
用HU治疗可增强SMA细胞中SMN2基因的表达，并在SMA患者的一些临床结局指标上显示出轻微的改善趋势，这表明HU在SMA患者中使用可能是安全的，但需要更大规模的随机、安慰剂对照、双盲试验来进一步研究其疗效。
