Neuromuscular Division, Department of Neurology, Wexner Medical Center, the Ohio State University, Columbus, OH; Department of Physical Medicine and Rehabilitation, Wexner Medical Center, the Ohio State University, Columbus, OH.
Ann Neurol. 2013 Sep;74(3):348-62. doi: 10.1002/ana.23995.
In neurodegenerative disorders, effective treatments are urgently needed, along with methods to determine whether treatment worked. In this review, we discuss the rapid progress in the understanding of recessive proximal spinal muscular atrophy and how this is leading to exciting potential treatments of the disease. Spinal muscular atrophy is caused by loss of the survival motor neuron 1 (SMN1) gene and reduced levels of SMN protein. The critical downstream targets of SMN deficiency that result in motor neuron loss are not known. However, increasing SMN levels has a marked impact in mouse models, and these therapeutics are rapidly moving toward clinical trials. Promising preclinical therapies, the varying degree of impact on the mouse models, and potential measures of treatment effect are reviewed. One key issue discussed is the variable outcome of increasing SMN at different stages of disease progression.
在神经退行性疾病中，迫切需要有效的治疗方法，以及确定治疗是否有效的方法。在这篇综述中，我们讨论了对隐性近端脊髓性肌萎缩症的理解的快速进展，以及这如何为该病的令人兴奋的潜在治疗方法提供了线索。脊髓性肌萎缩症是由生存运动神经元 1 (SMN1) 基因缺失和 SMN 蛋白水平降低引起的。导致运动神经元丧失的 SMN 缺乏的关键下游靶标尚不清楚。然而，增加 SMN 水平对小鼠模型有显著影响，这些治疗方法正在迅速进入临床试验。本文综述了有前景的临床前治疗方法、对小鼠模型的不同影响程度以及潜在的治疗效果评估方法。讨论的一个关键问题是在疾病进展的不同阶段增加 SMN 的结果不同。
