更新于：2024-11-01

Spinal Muscular Atrophy

脊髓性肌萎缩

更新于：2024-11-01

基本信息

别名

AMYOTROPHY, NEUROGENIC SCAPULOPERONEAL, NEW ENGLAND TYPE、Adult Onset Spinal Muscular Atrophy、Adult Spinal Muscular Atrophy

+ [146]

简介

A group of disorders marked by progressive degeneration of motor neurons in the spinal cord resulting in weakness and muscular atrophy, usually without evidence of injury to the corticospinal tracts. Diseases in this category include Werdnig-Hoffmann disease and later onset SPINAL MUSCULAR ATROPHIES OF CHILDHOOD, most of which are hereditary. (Adams et al., Principles of Neurology, 6th ed, p1089)

关联

项与脊髓性肌萎缩相关的药物

Risdiplam

利司扑兰

靶点

SMN2

作用机制

SMN2调节剂

在研机构

Hoffmann-La Roche, Inc. [+9]

原研机构

PTC Therapeutics, Inc.

在研适应症

脊髓性肌萎缩 [+3]

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2020-08-07

Onasemnogene abeparvovec

靶点

SMN1

作用机制

SMN1基因刺激剂

在研机构

Novartis Pharmaceuticals Corp. [+7]

原研机构

Novartis Gene Therapies, Inc. [+1]

在研适应症

I型脊髓性肌萎缩症 [+3]

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2019-05-24

Nusinersen sodium

诺西那生钠

靶点

SMN2

作用机制

SMN2刺激剂 [+1]

在研机构

Biogen, Inc. [+5]

原研机构

Ionis Pharmaceuticals, Inc.

在研适应症

神经肌肉疾病 [+1]

非在研适应症

I型脊髓性肌萎缩症

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2016-12-23

472

项与脊髓性肌萎缩相关的临床试验

NCT06555419 / Not yet recruiting临床1期

An Open Label, Single Cohort Study to Assess the Pharmacokinetic Profile of Nusinersen (BIIB058) Administered Via the ThecaFlex DRx™ System (PIERREPK)

In this PIERRE-PK study, researchers will learn how the body processes nusinersen when it is given through the ThecaFlex DRx™ System, compared to when nusinersen is given by lumbar puncture (LP). The ThecaFlex DRx system is an investigational implantable medical device developed by Alcyone Therapeutics, Inc. It consists of a catheter, which is a flexible tube, connected to a port which is placed under the skin. Alcyone Therapeutics, Inc. has an ongoing study called PIERRE to test the ThecaFlex DRx system. Participants with spinal muscular atrophy (SMA) in the PIERRE study may be enrolled in the PIERRE-PK study.
The main objective of the PIERRE-PK study is to learn how the body processes nusinersen when given by the ThecaFlex DRx system compared to a lumbar puncture. The main questions researchers want to answer are:
* What is the highest amount of nusinersen found in the blood after dosing?
* How much nusinersen is found in the blood over the first 24 hours after dosing?
The PIERRE-PK study will be done as follows:
* Participants will be screened to check if they can join the study. The screening period will be up to 30 days for this study and may overlap with the PIERRE study.
* Participants will receive a dose of nusinersen by lumbar puncture.
* The ThecaFlex DRx system will be implanted after the lumbar puncture, as part of the PIERRE study.
* Participants will receive a dose of nusinersen by the ThecaFlex DRx system, as part of the PIERRE study.
* Researchers will take blood samples before and after each dose. The last blood sample will be taken 24 hours after the dose.
* The total study duration for each participant in the PIERRE-PK study will be up to 5 months. This period will overlap with the participant's first 5 months in the PIERRE study.

开始日期2024-12-16

申办/合作机构

Biogen, Inc.

NCT06532474 / Not yet recruitingN/AIIT

Pilot Study Exploring the Physiologic, Pharmacodynamic, and Clinical Responses of Skeletal Muscle in Patients With Spinal Muscular Atrophy Treated With SMN-Directed Therapies

In this observational study, researchers are looking at the effects of spinal muscular atrophy (SMA) drugs on the muscles and nerve cells in patients with SMA.
Primary Objectives
* To evaluate the feasibility and reliability of performing MR functional imaging in exercising muscle in patients with SMA.
* To evaluate patients with SMA types 2 and 3 at baseline and longitudinally at 6 and 12 months
Secondary Objectives
* To describe the MR functional bioenergetics response in the leg muscles in four potential groups of patients with spinal muscular atrophy: untreated, actively treated with nusinersen (Spinraza®) or onasemnogene abeparvovec (Zolgensma®), actively treated with risdiplam (Evrysdi®), and switching from Spinraza or Zolgensma to Evrysdi.
* To identify changes in motor function in patients with SMA types 2 and 3 who initiate treatment with risdiplam.
* To obtain biomarkers in blood, urine, and muscle tissue to provide evidence for risdiplam effect on skeletal muscle.
* To obtain quality of life and disability data from participants in this study.

开始日期2024-11-01

申办/合作机构

St. Jude Children's Research Hospital, Inc.

[+1]

NCT06288230 / Recruiting临床1/2期

Study of AAV-hSMN1 (Vesemnogene Lantuparvovec) Gene Therapy in Subjects with Progressive Spinal Muscular Atrophy

This is an interventional study to evaluate safety and efficacy of AAV-hSMN1 in spinal muscular atrophy patients.

开始日期2024-10-20

申办/合作机构

Lantu Biopharma Inc.

100 项与脊髓性肌萎缩相关的临床结果

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100 项与脊髓性肌萎缩相关的转化医学

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0 项与脊髓性肌萎缩相关的专利（医药）

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14,412

项与脊髓性肌萎缩相关的文献（医药）

2025-02-01·Neurology Clinical Practice

Spinal Muscular Atrophy Update in Best Practices

Article

作者: Burnette, W Bryan ; Schroth, Mary K ; Deans, Jennifer ; Proud, Crystal M ; Darras, Basil T ; Bharucha Goebel, Diana X ; Veerapandiyan, Aravindhan ; Graham, Robert J ; Elsheikh, Bakri H ; Klein, Andrea ; Krueger, Jena ; Felker, Marcia V

Background and ObjectivesSpinal muscular atrophy (SMA) is an autosomal recessive disorder caused by biallelic variants of the Survival Motor Neuron 1 gene (SMN1) that affects approximately 1 in 15,000 live births. Availability of 3 SMN-enhancing treatments for SMA has led to urgency to review how clinicians and patients use these treatments for SMA, while additional research and real-world data and experience are being collected. This work describes important factors to assist with decision-making for SMN-enhancing treatments.MethodsA systematic literature review was conducted on SMN-enhancing treatments for SMA and related studies. A working group of American and European health care providers with expertise in SMA care identified barriers and developed recommendations through a modified Delphi technique with serial surveys and feedback through virtual meetings to fill gaps for information where evidence is limited. A community working group of an individual living with SMA and caregivers provided insight and perspective on SMA treatments and support through a virtual meeting to guide recommendations.ResultsThe health care provider working group and the community working group agreed that when determining whether to start, change, add, or discontinue a treatment, essential considerations include patient and family/caregiver perspective, and treatment safety and side effects. When initiating treatment for patients newly diagnosed with SMA, important patient characteristics are age and Survival Motor Neuron 2 gene (SMN2) copy number. Furthermore, when initiating, changing, or adding treatment, current clinical status and comorbidities drive decision-making. When considering a medication or treatment plan change, unless there is an urgent indication, a treatment and associated patient outcomes should be monitored for a minimum of 6-12 months. When determining a treatment plan with an adolescent or adult with SMA, consider factors such as quality of life, burden vs benefit of treatment, and reproductive issues. Access to care coordination and interdisciplinary/multidisciplinary care are essential to treatment success.DiscussionSharing information about current knowledge of treatments and shared decision-making between health care providers and patients living with SMA and caregivers are essential to overcoming barriers to providing SMN-enhancing treatments.

2025-02-01·Behavioural Brain Research

DNA methylation profiles of transgenerational rat hyperactivity primed by silver nanoparticles: Comparison with valproate model rats of autism

Article

作者: Higashi, Kouichi ; Mori, Hiroshi ; Ueno, Masaki ; Ishido, Masami ; Kurokawa, Ken

There is an increasing body of evidence suggesting that a single exposure to certain chemicals can have transgenerational effects, with the underlying mechanism believed to be epigenetic. However, it remains largely unknown whether psychiatric conditions like ADHD or autism, induced by environmental chemicals, can be inherited across generations. Pregnant rats were purchased from a commercial breeder. On the 7th day of gestation (E7), they were divided into two groups: one group was orally exposed to silver nanoparticles (AgNP; 4 mg/kg), while the control group received vehicle alone. The subsequent generation (F1) underwent spontaneous motor activity (SMA) measurements at 8-11 weeks of age. For breeding at 26 weeks of age, rats with higher SMA were selected from hyperactive litters, while untreated rats were randomly selected. This process was continued for four generations in both groups. The AgNP-primed rats at 4th generation displayed significantly higher SMA, 1.8 times greater than that of untreated rats. Intraperitoneal injection of valproic acid (150 mg/kg), an epigenetic modifier to 5-day-old rats causes adult hyperactivity (1.4-fold), suggesting that epigenetic modification contributes to rat hyperactivity. Global DNA methylation profiles in the mesencephalon were positively correlated in both groups of hyperactive rats. Furthermore, there were 7-8 common genes showing both hypermethylation and hypomethylation, which are involved in neuronal development, neuronal function, transcriptional activity, DNA binding activity, cell differentiation, ubiquitination processes, or histone modification, including Pax 6 and Mecp 2. Thus, it is most likely that rats retain hyperactivity through mesencephalic DNA methylation status across transgeneration.

2025-01-01·Vascular and Endovascular Surgery

Challenging Conventional Treatment: Retrograde Implantation of a Covered Stent in Superior Mensenteric Artery Occlusion Case

Article

作者: Jie, Zhang ; Zhao, Zeyi

Background: This case report describes a novel endovascular technique for treating superior mesenteric artery (SMA) occlusion, a condition leading to chronic mesenteric ischemia (CMI). Traditional treatment methods for CMI, primarily due to SMA stenosis, are often complex and risky, particularly for patients unsuitable for conventional surgery. Objective: This study details the application of retrograde recanalization followed by the deployment of a VIABAHN covered stent in a patient with complete SMA ostium occlusion. Methods: The procedure’s success in re-establishing mesenteric blood flow demonstrates its potential as a less invasive, safer alternative to traditional surgical approaches. This technique’s innovation lies in its retrograde approach, allowing for effective treatment in cases where antegrade access is unfeasible. Results: The patient showed significant symptom improvement without procedural complications, underscoring the method’s efficacy and safety. Conclusion: These findings suggest that retrograde stent implantation can be a viable option for managing SMA occlusions, especially in high-risk surgical cases. The successful application of this technique in this case contributes to the evolving landscape of endovascular interventions in vascular surgery and offers a promising direction for future research and clinical practice in treating SMA-related conditions.

1,524

项与脊髓性肌萎缩相关的新闻（医药）

2024-10-30

·PRNewswire

REGENXBIO to Host Conference Call on November 6 to Discuss Third Quarter 2024 Financial Results and Recent Operational Highlights

ROCKVILLE, Md., Oct. 30, 2024 /PRNewswire/ -- REGENXBIO Inc. (Nasdaq: RGNX) today announced that it will host a conference call on Wednesday, November 6, at 4:30 p.m. ET to discuss its financial results for the third quarter ended September 30, 2024, and recent operational highlights. Listeners can register for the webcast via this link. Analysts wishing to participate in the question and answer session should use this link. A replay of the webcast will be available via the company's investor website approximately two hours after the call's conclusion. Those who plan on participating are advised to join 15 minutes prior to the start time. ABOUT REGENXBIO Inc. REGENXBIO is a leading clinical-stage biotechnology company seeking to improve lives through the curative potential of gene therapy. Since its founding in 2009, REGENXBIO has pioneered the development of AAV Therapeutics, an innovative class of gene therapy medicines. REGENXBIO is advancing a pipeline of AAV Therapeutics for rare and retinal diseases, including RGX-202 for the treatment of Duchenne, ABBV-RGX-314 for the treatment of wet AMD and diabetic retinopathy, being developed in collaboration with AbbVie, and RGX-121 for the treatment of MPS II. Thousands of patients have been treated with REGENXBIO's AAV Therapeutic platform, including Novartis' Zolgensma® for children with spinal muscular atrophy. Designed to be one-time treatments, AAV Therapeutics have the potential to change the way healthcare is delivered for millions of people. For more information, please visit . Contacts: Dana Cormack Corporate Communications [email protected] Investors: George E. MacDougall Investor Relations [email protected] SOURCE REGENXBIO Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

基因疗法财报

2024-10-29

·空之客

【医苑观畴】2024年三季度海外药企进展更新：罗氏ROG

1 整体表现虎落平阳的肿瘤一哥罗氏，医药板块的业绩增长只能说看起来有了起色的一点微弱的迹象，因而市值也就只能在$250b左右徘徊不前。全年收入增长预计在mid single digit，EPS增长也就high single digit，就很符合欧洲的调性。 2 已上市产品罗氏的增量依然是几乎只来源于眼科单一品种Vabysmo，而在医药史上那一堆其灿如言的商品名，如今基本都已经成为下滑的来源。肿瘤板块实在是标准的英雄末路，从Rituximab到Atezolizumab这一堆说多都是泪，哪怕Kadcyla和Obinutuzumab也都陷入停滞，更令人失望的是两款身处末线的CD20/CD3双抗单季距离$100m都相去甚远，这一派萧瑟令人唯有扼腕；唯二还能看一看的品种，HER2复方抗体Phesgo还在不断替代市场、不过转化率已经爬到43%、与公司自称的50%目标距离也所剩无几，Polivy在这个季度突然跃升到$300m以上、在1L DLBCL的份额爬升到28%。自免板块纵不至于像肿瘤那样绝望，但增量也已经相当有限，CD20单抗Ocrelizumab的LTM累计接近$6.7b、已经基本上开始走平，尽管公司再次强调在皮下制剂获批后能带来新的增量，峰值看到$2b，且现在80%新患都开始用皮下剂型；IgE单抗Omalizumab在哮喘的份额不断被侵蚀、但公司斩钉截铁且不给任何解释地断定其生物类似药明年并不会出现，而IL6单抗Tocilizumab的生物类似药则已经快要杀到面前。最终扛住公司业绩的反倒是当年的闲棋冷子：眼科双抗Emicizumab目前还基本保持着线性的爬坡曲线，目前LTM累计已达到$3.6b，公司明确披露在AMD/DME/RVO等几个适应症的份额都还在持续提升，新患的份额已经提升到50%左右，看样子上个季度嘲讽的隔壁Eylea HD拿J-code确实尚未产生可见的“任何影响”，而且公司也明确表示Eylea生物类似药也并不会带来什么实质的影响、毕竟Avastin和Lucentis的生物类似药早已充斥了整个眼科市场；眼科下一个被寄予厚望的就是坎坷归来的Susvimo植入剂，公司给了今年几百、明年几千、后年上万的种植例数目标；血友病双抗Emicizumab看起来确实扛住了长效八因子的竞争冲击，重新进入增长轨道，目前LTM累计已达到$4.3b，未来还能维持5%增长；SMA药物Risdiplam如预期地在上个季度的招标等一次性因素之后，本季度环比有所回落，目前LTM累计已达到$1.6b；小惊喜的是基因治疗Elevidys获批后，已经迅速治疗了50多例，单季销售额也突破$100m。 3 在研管线首先就是PI3Kα抑制剂Inavolisib终于获得FDA批准治疗PIK3CA突变的HR+/HER2-乳腺癌，在PI3K哀鸿遍野（参见【药海听涛】PI3K之殇：确定性的不确定性？）和Roche在乳腺癌的霸权全面崩溃（参见【药海听涛】Roche已死，AZ当立？SABCS 2022回眸）的形式下，总算留下了一口气。紧接着还是在HR+HER2-乳腺癌上，Roche豪掷$850m首付款拿下齐鲁锐格的CDK2/4/6抑制剂RGT-419B，该药仍在临床一期，去年底SABCS公布过单药Ph1a剂量爬坡试验的初步结果，12例患者中做出了3例PR。除此以外，值得关注的进展还包括：获批消息包括PD-L1单抗Atezolizumab的皮下注射剂型，CD20单抗Ocrelizumab的半年一次皮下注射剂型，C5单抗Crovalimab在欧盟获批，Vabysmo在欧盟获批RVO适应症等；临床读出包括CD20单抗Obinutuzumab在狼疮肾炎的三期临床积极结果，BTK C481S抑制剂Fenebrutinib在多发性硬化症的三期临床结果，流感药物Baloxavir首个降低传染性的三期临床结果，SMN2药物Risdiplam针对儿童SMA的三期临床结果等；但更吸引眼球的反而是Roche不声不响的瘦身，一下抹掉了好多管线，其中还不乏TLR7和siRNA的乙肝管线、PD1/LAG3双抗、Tau单抗等多个曾经红极一时的热点方向。 4 有关减肥的审美疲劳在电话会最后，CEO居然戏剧性地对没人提问减肥相关问题进行了吐槽，仿佛小学生花了一晚上背课文却发现老师抽查没抽到自己的失落^_^ 罗氏总给人一种值得进商学院教科书的感觉，其兴也肿瘤、其落也肿瘤，最强大的能力铸就了曾经的辉煌、也可能恰恰成为眼下的桎梏，而打破它的方法是否就需要跳出那些舒适区呢？看起来，让这个在肿瘤领域叱咤风云凡二十余载的巨头走出困境，很有可能要靠眼科和减肥品种了？

生物类似药基因疗法

2024-10-28

·北海康成

北海康成成功获得《药品生产许可证》B证

中国苏州，2024年10月28日—北海康成制药有限公司（以下简称“北海康成”，股票代码“1228.HK”），是一家在中国领先并专注罕见疾病领域的全球化的生物制药公司，致力于创新疗法的研究、开发和商业化。公司今日宣布，已顺利通过药品上市许可持有人（MAH）的生产和质量管理体系审核和现场检查，获得由上海市药品监督管理局颁发的《药品生产许可证》B证。获得《药品生产许可证》B证标志着北海康成成为了一家具备药品研发、生产和销售的完整功能的生物制药公司；同时，作为生物药分段生产的试点企业，在监管部门的指导和帮助下，成功探索并实践了MAH对生物药分段生产的质量管理体系，为中国生物药分段生产未来的试点工作继续推进做出了我们应有的贡献。本次B证的获得具有重要里程碑意义，这为后续药物，如治疗成人和儿童I型和III型戈谢病的CAN103（注射用维拉苷酶β ）的NDA申报以及上市后商业化生产提供了重要前提条件，也是CAN103成为首个在中国本土研发和生产的酶替代疗法的重要环节，必将为北海康成持续释放创新活力与潜力提供广阔空间。《药品生产许可证》B证的取得说明了北海康成在公司组织架构、人员资质、药物生产和质量管理体系等方面已达到国家法律、法规的要求，完全有能力确保药品生产的质量和稳定性。凭借该许可证，我们具备了提交CAN103新药上市申请（NDA）的资质，CAN103有望成为北海康成在中国商业化的第三个罕见病治疗产品，同时也是首个内部研发的产品。向上滑动阅览北海康成制药有限公司（以下简称“北海康成”，股票代码1228.HK）是一家在中国领先并专注罕见疾病领域的全球化的生物制药公司，致力于创新疗法的研究、开发和商业化。公司目前拥有12个具有可观市场潜力的药物资产组合，其中包括3种已获批上市产品和9个在研药物。这些产品均针对一些较普遍的罕见疾病适应症，比如亨特氏综合征和其他溶酶体贮积症、补体介导的疾病、血友病 A、代谢紊乱、罕见的胆汁淤积性肝病、神经肌肉疾病。北海康成的新一代基因技术研发中心实验室正在开发针对罕见遗传病，包括庞贝氏症、法布雷病、脊髓性肌萎缩症（SMA）、杜氏肌肉营养不良症和其他神经肌肉疾病的新型及潜在治愈性的基因疗法，并与世界领先的研究人员和生物技术公司合作。公司的全球合作伙伴包括不限于 Apogenix、GC Pharma、Mirum、药明生物、Privus、UMass Chan医学院、华盛顿大学医学部和Scriptr Global 等。如需了解更多关于北海康成制药有限公司的信息，请访问：http://www.canbridgepharma.com/ 前瞻性声明：本文中作出的前瞻性陈述仅与本文作出陈述之日的事件或信息有关。除非法律要求，否则我们不承担公开更新或修改任何前瞻性陈述的义务，无论是由于新信息、未来事件或其他原因，在做出陈述的数据之后或反映意外事件的发生情况。您应完整阅读本文，并了解我们未来的实际结果或表现可能与我们的预期存在重大差异。在本文中，我们或我们的任何董事或我们公司的意图的陈述或引用均在本文发表之日作出。这些意图中的任何一个都可能随着未来的发展而改变。联系我们：投资者关系： ir@canbridgepharma.com

上市批准基因疗法申请上市