SMN Replacement Therapy for Spinal Muscular Atrophy: Clinical Development

SMN 替代疗法治疗脊髓性肌萎缩症：临床开发

• 批准号: G1001492/1
• 负责人: Mimoun Azzouz
• 金额: $ 94.32万
• 依托单位: University of Sheffield
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G1001492%2F1
• 关键词: SMN; Replacement; Therapy; Spinal; Muscular

SMA is due to premature death of motor neurons which are connected to muscle, and provide the stimulus to initiate muscle contraction. The disease is caused by depletion in the SMN protein levels. We recently showed that genetically modified viruses, making them safe to use in human, can be successfully used to restore the level of SMN both in cells and in a mouse model. The latest experiments showed for the first time that we can replace the SMN gene, reverse the symptoms leading to a dramatic effect on survival in the SMA mouse model. However, further in vivo studies are needed to characterise our strategy before entering clinical application in human. Our major goals are: 1) Optimise a method to produce large quantity of clinical grade vector; 2) select the appropriate dose for further safety studies in rodents; 3) Evaluate the safety and toxicity of our system. These studies represent an important and necessary step towards translation into human treatment.

SMA是由于与肌肉连接的运动神经元过早死亡，并提供刺激，启动肌肉收缩。这种疾病是由SMN蛋白水平下降引起的。我们最近展示了转基因病毒，使它们可以安全地用于人类，可以成功地用于恢复细胞和小鼠模型中的SMN水平。最新的实验首次表明，我们可以替换SMN基因，逆转导致SMA小鼠模型存活的显著影响的症状。然而，在进入人体临床应用之前，需要进一步的体内研究来表征我们的策略。我们的主要目标是：1)优化一种生产大量临床级载体的方法；2)选择合适的剂量，用于进一步的啮齿动物安全性研究；3)评估我们系统的安全性和毒性。这些研究是向转化为人类治疗迈出的重要而必要的一步。