SMN蛋白数量的不足是遗传性神经肌肉疾病脊髓性肌萎缩症（SMA）的原因，为了弥补SMN蛋白数量的不足，研究人员已经成功直接递送SMN1基因到SMA动物模型的脊髓中。

一项新的研究表明足够的SMN1基因副本可以被递送到脊髓运动神经元中，延长治疗动物的生存，相关研究论文发表在Human Gene Therapy杂志上。

Marco Passini和合作者用腺相关病毒载体作为运载工具，通过鞘内输送，递送SMN1基因拷贝到脊髓运动神经元中。

研究报告了恢复正常猪和非人灵长类SMA模型的功能性SMN蛋白水平的有效性，将预测在真正的小鼠模型中基于相同载体递送基因对于疾病治疗的有效性。

James M. Wilson博士表示：这是一个非常有前途的一组临床前研究，将帮助研究成果快速转换到临床上。 

原文：

Translational Fidelity of Intrathecal Delivery of Self-Complementary AAV9-Survival Motor Neuron 1 for Spinal Muscular Atrophy.

Passini MA1, Bu J, Richards AM, Treleaven CM, Sullivan JA, O'Riordan CR, Scaria A, Kells AP, Samaranch L, San Sebastian W, Federici T, Fiandaca MS, Boulis NM, Bankiewicz KS, Shihabuddin LS, Cheng SH.

Abstract Spinal muscular atrophy (SMA) is a neuromuscular disease caused by mutations in survival motor neuron 1 (SMN1). Previously, we showed that central nervous system (CNS) delivery of an adeno-associated viral (AAV) vector encoding SMN1 produced significant improvements in survival in a mouse model of SMA. Here, we performed a dose-response study in SMA mice to determine the levels of SMN in the spinal cord necessary for efficacy, and measured the efficiency of motor neuron transduction in the spinal cord after intrathecal delivery in pigs and nonhuman primates (NHPs). CNS injections of 5e10, 1e10, and 1e9 genome copies (gc) of self-complementary AAV9 (scAAV9)-hSMN1 into SMA mice extended their survival from 17 to 153, 70, and 18 days, respectively. Spinal cords treated with 5e10, 1e10, and 1e9 gc showed that 70-170%, 30-100%, and 10-20% of wild-type levels of SMN were attained, respectively. Furthermore, detectable SMN expression in a minimum of 30% motor neurons correlated with efficacy. A comprehensive analysis showed that intrathecal delivery of 2.5e13 gc of scAAV9-GFP transduced 25-75% of the spinal cord motor neurons in NHPs. Thus, the extent of gene expression in motor neurons necessary to confer efficacy in SMA mice could be obtained in large-animal models, justifying the continual development of gene therapy for SMA.