A Study of valproic acid for patients with spinal muscular atrophy.
A Study of valproic acid for patients with spinal muscular atrophy.
复制标题
丙戊酸治疗脊髓性肌萎缩症患者的研究。
DOI：
10.1111/ncn3.140
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发表时间：
2015
影响因子：
0.4
通讯作者：
Nishio H.
中科院分区：
文献类型：
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作者：
Saito T;Nurputra DK;Harahap NI;Harahap IS;Yamamoto H;Muneshige E;Nisizono H;Matsumura T;Fujimura H;Sakoda S;Saito K;Nishio H.
目的评价丙戊酸(VPA)治疗脊髓性肌萎缩症(SMA)的疗效。其中6例为II型(A-E、G)，1例为II3型(F例)。1例女性患者(病例E)年龄2岁10个月，其他患者年龄15岁至42岁。用L-卡尼汀治疗6个月。治疗前、治疗后1、3、6个月分别进行外周血白细胞SMN转录本分析，并采用改良Hammersmith SMA功能运动评分(MHFMS)、肺活量(VC)、最大通气量(MIC)、咳嗽高峰流量(CPF)进行评定。B-D和G组的VPA终剂量为400 mg/d，而E组的终剂量为100 mg/d。FL-SMN转录产物数量呈增加趋势。病例E的MHFMS有明显改善，并在研究期间获得了左右翻转的运动功能。老年患者MHFMS虽无明显变化，但VC、MIC和CPF均有改善。结论VPA治疗对改善部分SMA患者的MHFMS和呼吸功能是有效的。有必要进行安慰剂对照的随机试验，以确认VPA对SMA的疗效。
BackgroundValproic acid (VPA) is expected to become an effective therapeutic agent for spinal muscular atrophy (SMA) because of its histone deacetylase inhibitor effect.AimTo evaluate the effectiveness of VPA for SMA.MethodsSeven consecutive Japanese SMA patients (three males, four females) were recruited. Of those, six were type 2 (cases A–E, G) and one was type 3 (case F). One female patient (case E) was aged 2 years and 10 months, whereas the others ranged in age from 15 to 42 years. VPA was administered for 6 months with L‐carnitine. We carried outSMNtranscript analysis of peripheral white blood cells, and evaluated using the Modified Hammersmith Functional Motor Scale for SMA (MHFMS), vital capacity (VC), maximum insufflation capacity (MIC), and cough peak flow (CPF) before and at 1, 3 and 6 months after starting treatment.ResultsCases B–E and G completed the study. The final VPA dosage in cases B–D and G was 400 mg/day, whereas that in case E was 100 mg/day. The quantity of the FL‐SMNtranscription product showed a tendency to increase. Case E showed a remarkable improvement in MHFMS, and gained motor function to turn from side to side during the study period. Although no significant changes were observed in MHFMS in the older cases, VC, MIC and CPF were improved in those.ConclusionOur findings suggest that VPA treatment is effective for improving MHFMS and respiratory function in some SMA patients. A placebo‐controlled randomized trial is warranted to confirm the efficacy of VPA for SMA.