The prospects of targeting DUX4 in facioscapulohumeral muscular dystrophy.
The prospects of targeting DUX4 in facioscapulohumeral muscular dystrophy.
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DOI：
10.1097/wco.0000000000000849
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发表时间：
2020-10
影响因子：
4.8
通讯作者：
de Greef JC
中科院分区：
文献类型：
--
作者：
Bouwman LF;van der Maarel SM;de Greef JC
面肩肱型肌营养不良症 (FSHD) 是一种神经肌肉疾病，由骨骼肌中转录因子 DUX4 的不完全抑制引起。迄今为止，尚无 DUX4 靶向治疗方法可以预防或延缓疾病进展。在这篇综述中，我们总结了治疗策略的进展，重点是抑制 DUX4 和 DUX4 靶基因表达。不同的研究表明，DUX4 及其靶基因可以通过采用不同策略的基因疗法来抑制。此外，不同的小化合物可以在体外和体内降低DUX4及其靶基因。大多数显示基因疗法抑制 DUX4 的研究仅在体外进行过测试。应付出更多努力来测试它们的临床转化。多种化合物已被证明可以在体外和体内阻止 DUX4 和靶基因表达。然而，它们的效率和特异性尚未显示。随着临床试验的不断涌现，DUX4 抑制对 FSHD 的临床益处可能很快就会显现出来。
Facioscapulohumeral muscular dystrophy (FSHD) is a neuromuscular disorder that is caused by incomplete repression of the transcription factor DUX4 in skeletal muscle. To date, there is no DUX4-targeting treatment to prevent or delay disease progression. In this review, we summarize developments in therapeutic strategies with the focus on inhibiting DUX4 and DUX4 target gene expression. Different studies show that DUX4 and its target genes can be repressed with genetic therapies using diverse strategies. Additionally, different small compounds can reduce DUX4 and its target genes in vitro and in vivo. Most studies that show DUX4 repression by genetic therapies have only been tested in vitro. More efforts should be made to test them in vivo for clinical translation. Several compounds have been shown to prevent DUX4 and target gene expression in vitro and in vivo. However, their efficiency and specificity has not yet been shown. With emerging clinical trials, the clinical benefit from DUX4 repression in FSHD will likely soon become apparent.