Therapeutic interventions for disease progression in Huntington's disease.
Therapeutic interventions for disease progression in Huntington's disease.
复制标题
亨廷顿病疾病进展的治疗干预措施。
DOI：
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发表时间：
2009
影响因子：
8.4
通讯作者：
C. Sampaio
中科院分区：
文献类型：
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作者：
T. Mestre;J. Ferreira;M. Coelho;M. Rosa;C. Sampaio
背景
亨廷顿病(HD)是一种常染色体显性遗传性神经退行性疾病，平均发病时间在生命的第四到第五个十年之间；它会在症状出现15到20年后导致死亡。尽管有几种药物似乎对控制HD的丧失能力表现有效，但目前还没有特效的治疗方法。本审查旨在分析所调查的治疗干预措施的最佳现有数据，目的是根据HD核心症状的存活、残疾或进展来衡量疾病的进展情况。
目标
评估旨在改变HD疾病进展的治疗干预措施的有效性。
搜索策略
采取了为行动障碍小组制定的搜索战略。对Cochrane对照试验注册、Medline、EMBASE和美国国家卫生研究所的临床试验数据库进行了彻底搜索，直到2007年12月。
遴选标准
所有随机、双盲、安慰剂对照的治疗学临床试验均纳入研究，目的是改变HD的疾病进展。参与者应具有经基因确诊的HD或相关症状和家族病史。试验的随访期超过三个月，至少有十名参与者。所有的药理学和非药理学干预措施都包括在内。
数据收集和分析
两名审查员独立评估了已确定的试验的资格。对方法质量进行了评估，并将合格的数据登记到标准化表格中。如果可行，进行意向治疗分析。如果原始出版物中没有数据，则联系试验的首席调查员以获得进一步的信息。如有可能，应进行荟萃分析；否则，将提供结果的描述性摘要。采用Revman 5.0.15软件进行统计分析。
主要成果
共纳入8项试验，涉及1366名HD患者。研究持续时间从30周到144周不等(中位数：52周)。干预措施如下：维生素E、艾德贝农、巴氯芬、拉莫三嗪、肌酸、辅酶Q10+瑞马西胺、二十碳五酸乙酯和利鲁唑。对于选定的疗效结果衡量标准，没有试验产生阳性结果。提供了试验的描述性摘要。选定的干预措施被发现总体上是安全的，耐受性良好。
作者的结论
只有药物干预被纳入，没有一项被证明是HD的疾病修正疗法。应使用更敏感的生物标志物进行方法学质量更高的进一步试验。未来的研究应该包括有症状的突变携带者。
BACKGROUND
Huntington's disease (HD) is an autosomal dominant neurodegenerative disease with an average onset between the fourth and fifth decade of life; it leads to death 15 to 20 years after the onset of symptoms. Although several drugs seem effective in controlling the incapacitating manifestations of HD, no specific therapy is known. The present review aims at analysing the best available data on therapeutic interventions investigated with the goal of modifying the progression of the disease as measured in terms of survival, disability or progression of HD core symptoms.
OBJECTIVES
Evaluate the effectiveness of therapeutic interventions aimed at modifying disease progression in HD.
SEARCH STRATEGY
The search strategy developed for the Movement Disorders Group was undertaken. The Cochrane Controlled Trials Register, Medline, EMBASE and Clinical Trials Database of the United States National Institute of Health were thoroughly searched until December 2007.
SELECTION CRITERIA
All randomised, double-blinded, placebo-controlled clinical trials of therapeutics investigated with the goal of modifying disease progression in HD were included. Participants should have genetically confirmed diagnosis of HD or compatible symptoms and a family history. Trials had a follow-up duration of more than three months and at least ten participants. All pharmacological and non-pharmacological interventions were included.
DATA COLLECTION AND ANALYSIS
Two reviewers independently assessed the eligibility of identified trials. The methodological quality was assessed and eligible data were registered onto standardised forms. An intention-to-treat analysis was conducted, when feasible. If data were not available in the original publication, the principal investigator of the trial was contacted for further information. A meta-analysis was to be conducted when possible; otherwise, a descriptive summary of the results was provided. The software Revman 5.0.15 was used for statistical analysis.
MAIN RESULTS
Eight trials were included involving a total of 1366 HD patients. The duration of the studies ranged between 30 and 144 weeks (median: 52 weeks). The following interventions were selected: vitamin E, Idebenone, Baclofen, Lamotrigine, creatine, coenzyme Q10 + Remacemide, ethyl-eicosapentanoic acid and Riluzole. No trials produced positive results for the selected efficacy outcome measures. A descriptive summary of the trials is provided. The selected interventions were found to be generally safe and well tolerated.
AUTHORS' CONCLUSIONS
Only pharmacological interventions were included and none proved to be effective as a disease-modifying therapy for HD. Further trials with greater methodological quality should be conducted using more sensitive biological markers. Pre-symptomatic mutation carriers should be included in future studies.
影响因子：
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作者：
J. C. Morris;R. Mohs;H. Rogers;G. Fillenbaum;A. Heyman
通讯作者：
J. C. Morris;R. Mohs;H. Rogers;G. Fillenbaum;A. Heyman