Nusinersen
(Synonyms: 寡核苷酸) 目录号 : GC64293
Nusinersen是一种反义寡核苷酸药物，修饰 SMN2 基因的前信使 RNA 剪接，从而促进全长SMN蛋白的生成。
Cas No.:1258984-36-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Nusinersen is an antisense oligonucleotide drug that modifies pre-messenger RNA splicing of the SMN2 gene and thus promotes increased production of full-length SMN protein[1].
Nusinersen is an SMN-ASO that increases SMN levels by blocking an intronic splice silencer in SMN2, thereby facilitating the exon 7 inclusion and generation of FL-SMN2 transcripts[2].
[1]. Richard S Finkel, et al. Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy. N Engl J Med. 2017 Nov 2;377(18):1723-1732.
[2]. Laura Torres-Benito, et al. NCALD Antisense Oligonucleotide Therapy in Addition to Nusinersen further Ameliorates Spinal Muscular Atrophy in Mice. Am J Hum Genet. 2019 Jul 3;105(1):221-230.
| Cas No. | 1258984-36-9 | SDF | Download SDF |
| 别名 | 寡核苷酸 | ||
| 分子式 | C234H340N61O128P17S17 | 分子量 | 7127.30 |
| 溶解度 | 储存条件 | -20°C, stored under nitrogen, away from moisture | |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 0.1403 mL | 0.7015 mL | 1.4031 mL |
| 5 mM | 0.0281 mL | 0.1403 mL | 0.2806 mL |
| 10 mM | 0.014 mL | 0.0702 mL | 0.1403 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy
N Engl J Med 2017 Nov 2;377(18):1723-1732.PMID:29091570DOI:10.1056/NEJMoa1702752.
Background: Spinal muscular atrophy is an autosomal recessive neuromuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonucleotide drug that modifies pre-messenger RNA splicing of the SMN2 gene and thus promotes increased production of full-length SMN protein. Methods: We conducted a randomized, double-blind, sham-controlled, phase 3 efficacy and safety trial of Nusinersen in infants with spinal muscular atrophy. The primary end points were a motor-milestone response (defined according to results on the Hammersmith Infant Neurological Examination) and event-free survival (time to death or the use of permanent assisted ventilation). Secondary end points included overall survival and subgroup analyses of event-free survival according to disease duration at screening. Only the first primary end point was tested in a prespecified interim analysis. To control the overall type I error rate at 0.05, a hierarchical testing strategy was used for the second primary end point and the secondary end points in the final analysis. Results: In the interim analysis, a significantly higher percentage of infants in the Nusinersen group than in the control group had a motor-milestone response (21 of 51 infants [41%] vs. 0 of 27 [0%], P<0.001), and this result prompted early termination of the trial. In the final analysis, a significantly higher percentage of infants in the Nusinersen group than in the control group had a motor-milestone response (37 of 73 infants [51%] vs. 0 of 37 [0%]), and the likelihood of event-free survival was higher in the Nusinersen group than in the control group (hazard ratio for death or the use of permanent assisted ventilation, 0.53; P=0.005). The likelihood of overall survival was higher in the Nusinersen group than in the control group (hazard ratio for death, 0.37; P=0.004), and infants with a shorter disease duration at screening were more likely than those with a longer disease duration to benefit from Nusinersen. The incidence and severity of adverse events were similar in the two groups. Conclusions: Among infants with spinal muscular atrophy, those who received Nusinersen were more likely to be alive and have improvements in motor function than those in the control group. Early treatment may be necessary to maximize the benefit of the drug. (Funded by Biogen and Ionis Pharmaceuticals; ENDEAR ClinicalTrials.gov number, NCT02193074 .).
Nusinersen for the treatment of spinal muscular atrophy
Expert Rev Neurother 2017 Oct;17(10):955-962.PMID:28884620DOI:10.1080/14737175.2017.1364159.
Spinal muscular atrophy (SMA) is an autosomal recessive degenerative neuromuscular disorder characterized by loss of spinal motor neurons leading to muscle weakness. This review article focuses on a novel antisense oligonucleotide treatment, first ever approved for SMA (Nusinersen, SpinrazaTM) and describes the exciting journey from early ASO clinical trials to regulatory approval of the first ever known effective treatment for SMA. Areas covered: This article reviews the results of the published open label Nusinersen studies in infants and children, and briefly covers the preliminary findings of the recently completed but as yet unpublished nusinersen-sham controlled trials, as well as the presymptomatic Nusinersen trial known as Nurture. Clinical use of Nusinersen is also reviewed. Expert commentary: Collectively, the studies show improvement in motor function across SMA of all types, including SMA type 3. Best motor response was observed with early treatment; presymptomatic treatment prevented disease manifestations. Nusinersen was found to be safe and well tolerated across all age groups studied. Nusinersen has irrevocably altered the natural history of SMA and allowed for the first time children to transition between SMA types. Nusinersen should be considered as standard of care for the treatment of SMA of all types.
Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy
N Engl J Med 2018 Feb 15;378(7):625-635.PMID:29443664DOI:10.1056/NEJMoa1710504.
Background: Nusinersen is an antisense oligonucleotide drug that modulates pre-messenger RNA splicing of the survival motor neuron 2 ( SMN2) gene. It has been developed for the treatment of spinal muscular atrophy (SMA). Methods: We conducted a multicenter, double-blind, sham-controlled, phase 3 trial of Nusinersen in 126 children with SMA who had symptom onset after 6 months of age. The children were randomly assigned, in a 2:1 ratio, to undergo intrathecal administration of Nusinersen at a dose of 12 mg (Nusinersen group) or a sham procedure (control group) on days 1, 29, 85, and 274. The primary end point was the least-squares mean change from baseline in the Hammersmith Functional Motor Scale-Expanded (HFMSE) score at 15 months of treatment; HFMSE scores range from 0 to 66, with higher scores indicating better motor function. Secondary end points included the percentage of children with a clinically meaningful increase from baseline in the HFMSE score (≥3 points), an outcome that indicates improvement in at least two motor skills. Results: In the prespecified interim analysis, there was a least-squares mean increase from baseline to month 15 in the HFMSE score in the Nusinersen group (by 4.0 points) and a least-squares mean decrease in the control group (by -1.9 points), with a significant between-group difference favoring Nusinersen (least-squares mean difference in change, 5.9 points; 95% confidence interval, 3.7 to 8.1; P<0.001). This result prompted early termination of the trial. Results of the final analysis were consistent with results of the interim analysis. In the final analysis, 57% of the children in the Nusinersen group as compared with 26% in the control group had an increase from baseline to month 15 in the HFMSE score of at least 3 points (P<0.001), and the overall incidence of adverse events was similar in the Nusinersen group and the control group (93% and 100%, respectively). Conclusions: Among children with later-onset SMA, those who received Nusinersen had significant and clinically meaningful improvement in motor function as compared with those in the control group. (Funded by Biogen and Ionis Pharmaceuticals; CHERISH ClinicalTrials.gov number, NCT02292537 .).
Safety and efficacy of Nusinersen in spinal muscular atrophy: The EMBRACE study
Muscle Nerve 2021 May;63(5):668-677.PMID:33501671DOI:10.1002/mus.27187.
Introduction: The EMBRACE study (Clinical Trials No. NCT02462759) evaluated Nusinersen in infants/children with infantile- or later-onset spinal muscular atrophy (SMA) who were ineligible for the ENDEAR and CHERISH studies. Methods: Participants were randomized to intrathecal Nusinersen (12-mg scaled equivalent dose; n = 14) or sham procedure (n = 7) in part 1 (~14 months) and subsequently received open-label Nusinersen for ~24 months in part 2 of the study. Results: Part 1 was stopped early after the demonstration of motor function benefit with Nusinersen in ENDEAR. There were no nusinersen-related adverse events (AEs) and no study discontinuations due to nusinersen-related AEs. The most common AEs included pyrexia, cough, pneumonia, and upper respiratory tract infections. Motor milestone responder rates were higher in those receiving Nusinersen at last available assessment (93%) than in those receiving sham procedure in part 1 (29%) or transitioned from sham to Nusinersen in part 2 (83%). This functional improvement was observed despite the small sample size and shortened part 1 trial duration that undermined the power of the study to demonstrate such treatment effects at a significant level. Discussion: Nusinersen demonstrated a favorable long-term benefit-risk profile in this broad population of individuals with infantile- or later-onset SMA.
Nusinersen as a Therapeutic Agent for Spinal Muscular Atrophy
Yonsei Med J 2020 Apr;61(4):273-283.PMID:32233169DOI:10.3349/ymj.2020.61.4.273.
The reduction of survival motor neuron (SMN) protein causes spinal muscular atrophy (SMA), an autosomal recessive neuromuscular disease. Nusinersen is an antisense oligonucleotide, approved by the FDA, which specifically binds to the repressor within SMN2 exon 7 to enhance exon 7 inclusion and augment production of functional SMN protein. Nusinersen is the first new oligonucleotide-based drug targeting the central nervous system for the treatment of SMA. This review of Nusinersen will discuss its action mechanism, cellular uptake, trafficking mechanisms, and administration approaches to cross the blood-brain barrier. Furthermore, Nusinersen clinical trials will be assessed in terms of pharmacokinetics, tolerability and safety, the clinical outcomes of multiple intrathecal doses, and a discussion on the primary and secondary endpoints.