VALPROIC ACID IN AMBULANT ADULTS WITH SMA

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项研究的主要目的是通过一项前瞻性、随机、两期交叉、双盲、安慰剂对照试验，确定口服丙戊酸(VPA)6个月是否会改善成年脊髓性肌萎缩症(SMA)患者的力量和功能。这项研究将涉及36名患者，所有患者都将在俄亥俄州立大学登记。受试者将被随机分配在前六个月接受VPA或安慰剂治疗，之后患者将被交叉分配到另一组(即，所有患者将接受至少六个月的药物治疗)。所有受试者将每隔3个月(3个月、6个月、9个月和12个月)进行评估，主要结果是通过计算机肌肉测试评估肌肉力量的变化。要检查的次要结果包括肺功能、通过定时行走、楼梯踏步评估的运动功能、有效的功能评定量表、生活质量问卷、电生理参数、疾病的遗传和生化标记物(即存活运动神经元mRNA和蛋白水平)以及通过双能X射线吸收法评估的肌肉质量。 这项研究是基于一种假设，即VPA等组蛋白去乙酰酶抑制剂上调SMN2的基因表达，这可以部分补偿导致疾病的SMN1基因缺失。这项研究的积极结果不仅将为SMA提供第一个有效的治疗方法，而且还将为这种方法提供原则证据，并导致对这种疾病的进一步临床试验。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The primary objective of the study is to determine through a prospective, randomized, two-period crossover, double- blinded, placebo- controlled trial whether valproic acid (VPA) given orally for six months will improve strength and function in adult patients with spinal muscular atrophy (SMA). The study will involve 36 patients, all to be enrolled at Ohio State. Subjects will be randomly assigned to receive VPA or placebo for the first six months following which patients will be crossed over to the other group (i.e., all patients will receive drug for at least six months). All subjects will be evaluated at three months intervals (3, 6, 9 and 12 months), with the primary outcome being change in muscle strength assessed through computerized muscle testing. Secondary outcomes to be examined include pulmonary function, motor function assessed through timed walking, stair clinbing, and a validated functional rating scale, quality of life questionaire, electrophysiologic parameters, genetic and biochemical markers for the disease (ie survival motor neuron mRNA and protein levels), and muscle mass as assesssed through dual energy x-ray absorptiometry. The study is based on the hypothesis that histone deacetylase inhibitors like VPA up regulate gene expression of SMN2, which can partially compensate for the SMN1 gene deletion that causes the disease. A positive result in this study will not only provide the first effective treatment for SMA, but will also provide proof of principle" for this approach and lead to further clinical trials in this disorder.