The First Orally Deliverable Small Molecule for the Treatment of Spinal Muscular Atrophy.
The First Orally Deliverable Small Molecule for the Treatment of Spinal Muscular Atrophy.
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DOI：
10.1177/2633105520973985
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发表时间：
2020
影响因子：
3.6
通讯作者：
Singh NN
中科院分区：
文献类型：
--
作者：
Singh RN;Ottesen EW;Singh NN
脊髓性肌萎缩症(SMA)是婴儿死亡的主要原因之一。SMA主要是由于SMN1基因的缺失或突变导致低水平的存活运动神经元(SMN)蛋白所致。其几乎完全相同的拷贝Smn2未能弥补由于主要跳过外显子7而导致的Smn1的丢失。针对内含子剪接沉默蛋白N1(ISS-N1)的反义寡核苷酸(Spinraza™)纠正Smn2外显子7的剪接成为第一个被批准的治疗方法。其次是使用基因疗法恢复SMN水平。最近，一种可口服的小分子药物risplam(Evrysdi™)成为第三种被批准的治疗方法。在这里，我们讨论这些疗法如何定位，以满足广泛的表型谱的SMA患者的需求。
Spinal muscular atrophy (SMA) is 1 of the leading causes of infant mortality. SMA is mostly caused by low levels of Survival Motor Neuron (SMN) protein due to deletion of or mutation in the SMN1 gene. Its nearly identical copy, SMN2, fails to compensate for the loss of SMN1 due to predominant skipping of exon 7. Correction of SMN2 exon 7 splicing by an antisense oligonucleotide (ASO), nusinersen (Spinraza™), that targets the intronic splicing silencer N1 (ISS-N1) became the first approved therapy for SMA. Restoration of SMN levels using gene therapy was the next. Very recently, an orally deliverable small molecule, risdiplam (Evrysdi™), became the third approved therapy for SMA. Here we discuss how these therapies are positioned to meet the needs of the broad phenotypic spectrum of SMA patients.
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作者：
Ahmad S;Bhatia K;Kannan A;Gangwani L
通讯作者：
Gangwani L
影响因子：
11.2
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