Antisense oligonucleotide therapies for Amyotrophic Lateral Sclerosis: Existing and emerging targets
Antisense oligonucleotide therapies for Amyotrophic Lateral Sclerosis: Existing and emerging targets
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DOI：
10.1016/j.biocel.2019.03.009
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发表时间：
2019-05-01
影响因子：
4
通讯作者：
Scotter, Emma L.
中科院分区：
文献类型：
--
作者：
Klim, Joseph R.;Vance, Caroline;Scotter, Emma L.
肌萎缩侧索硬化症（ALS）是一种具有高度异质性原因的疾病，其中大部分原因尚不清楚，有许多可能的疾病机制，目前没有可以阻止疾病进展的治疗方法。然而，反义寡核苷酸的最新进展使其成为患者靶向治疗的可行选择。这些分子提供了一种靶向RNA的方法，该方法具有高度特异性，适应性强，并且不需要病毒递送。因此，反义寡核苷酸正在开发用于ALS的几种遗传原因。此外，参与疾病发病机制的生物学途径也为使用反义寡核苷酸进行干预提供了诱人的靶点。在这里，我们详细介绍了ALS中反义寡核苷酸的现有和潜在靶点，并简要介绍了这些药物在临床上达到和有效的要求。
Amyotrophic lateral sclerosis (ALS) is a disease with highly heterogenous causes, most of which remain unknown, a multitude of possible disease mechanisms, and no therapy currently available that can halt disease progression. However, recent advances in antisense oligonucleotides have made them a viable option for targeted therapeutics for patients. These molecules offer a method of targeting RNA that is highly specific, adaptable, and does not require viral delivery. Antisense oligonucleotides are therefore being developed for several genetic causes of ALS. Furthermore, biological pathways involved in the pathogenesis of disease also offer tantalizing targets for intervention using antisense oligonucleotides. Here we detail existing and potential targets for antisense oligonucleotides in ALS and briefly examine the requirements for these drugs to reach and be effective in clinic.