VALPROIC ACID IN AMBULANT ADULTS WITH SMA

这个子项目是众多研究子项目之一

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.