Abstract：
The recent advances in nucleic acid therapeutics demonstrate the potential to treat hereditary neurological disorders by targeting their causative genes. Spinal and bulbar muscular atrophy (SBMA) is an X-linked and adult-onset neurodegenerative disorder caused by the expansion of trinucleotide cytosine-adenine-guanine repeats, which encodes a polyglutamine tract in the androgen receptor gene. SBMA belongs to the family of polyglutamine diseases, in which the use of nucleic acids for silencing a disease-causing gene, such as antisense oligonucleotides and small interfering RNAs, has been intensively studied in animal models and clinical trials. A unique feature of SBMA is that both motor neuron and skeletal muscle pathology contribute to disease manifestations, including progressive muscle weakness and atrophy. As both motor neurons and skeletal muscles can be therapeutic targets in SBMA, nucleic acid-based approaches for other motor neuron diseases and myopathies may further lead to the development of a treatment for SBMA. Here, we review studies of nucleic acid-based therapeutic approaches in SBMA and related neurological disorders and discuss current limitations and perspectives to apply these approaches to patients with SBMA.
摘要：
核酸疗法的最新进展证明了通过靶向其致病基因来治疗遗传性神经系统疾病的潜力。脊髓和延髓性肌萎缩症（SBMA）是一种X连锁和成人发作的神经退行性疾病，由三核苷酸胞嘧啶-腺嘌呤-鸟嘌呤重复序列的扩展引起，它在雄激素受体基因中编码一个多聚谷氨酰胺束。SBMA属于多谷氨酰胺疾病家族，其中使用核酸沉默致病基因，如反义寡核苷酸和小干扰RNA，在动物模型和临床试验中进行了深入研究。SBMA的一个独特特征是运动神经元和骨骼肌病理都有助于疾病表现，包括进行性肌肉无力和萎缩.由于运动神经元和骨骼肌都可以成为SBMA的治疗靶标，其他运动神经元疾病和肌病的基于核酸的方法可能进一步导致SBMA治疗的发展。这里,我们回顾了SBMA和相关神经系统疾病中基于核酸的治疗方法的研究，并讨论了目前的局限性和将这些方法应用于SBMA患者的观点。
