预约演示

更新于：2025-01-23

Muscular Dystrophy, Emery-Dreifuss

Emery-Dreifuss肌营养不良症

更新于：2025-01-23

基本信息

别名

Autosomal Recessive Emery Dreifuss Muscular Dystrophy、Autosomal Recessive Emery-Dreifuss Muscular Dystrophy、Autosomal recessive Emery-Dreifuss muscular dystrophy

+ [53]

简介

A heterogenous group of inherited muscular dystrophy without the involvement of nervous system. The disease is characterized by MUSCULAR ATROPHY; MUSCLE WEAKNESS; CONTRACTURE of the elbows; ACHILLES TENDON; and posterior cervical muscles; with or without cardiac features. There are several INHERITANCE PATTERNS including X-linked (X CHROMOSOME), autosomal dominant (for LMNA-associated type see AUTOSOMAL EMERY-DREIFUSS MUSCULAR DYSTROPHY), and autosomal recessive gene mutations.

关联

项与 Emery-Dreifuss肌营养不良症相关的药物

SAT-3153

靶点

AAK1 x Protein kinases

作用机制

AAK1抑制剂 [+2]

在研机构

Satellos Bioscience, Inc.

原研机构

Satellos Bioscience, Inc.

在研适应症

杜氏肌营养不良症 [+1]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

AAV gene therapy (Sarepta/Columbia University)

靶点-

作用机制

基因转移

在研机构

Sarepta Therapeutics, Inc. [+1]

原研机构

Sarepta Therapeutics, Inc.

在研适应症

Emery-Dreifuss肌营养不良症

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

项与 Emery-Dreifuss肌营养不良症相关的临床试验

NCT05394506

/ RecruitingN/AIIT

Identification of Genetic Modifying Factors in Striated Muscle Laminopathies

Mutations in the LMNA gene, which codes for lamins A and C, proteins of the nuclear lamina, are responsible for a wide spectrum of pathologies, including a group specifically affecting striated skeletal and cardiac muscles, with cardiac involvement being life-threatening. At the skeletal muscle level, a wide phenotypic spectrum has been described, ranging from severe forms of congenital muscular dystrophy to less severe forms of limb-girdle muscular dystrophy. The great clinical variability of striated muscle laminopathies, both inter- and intra-familial, can be observed in the age of onset, severity of signs and progression of muscle and heart involvement. To date, more than 400 LMNA mutations have been associated with striated muscle laminopathies (www.umd.be/LMNA/), highlighting strong clinical and genetic heterogeneity. A few recurrent mutations linked to a difference in severity have been identified. However, these genotype-phenotype relationships and the rare cases of digenism reported do not explain all the clinical variability of laminopathies. Therefore, there are probably other factors of severity than the causative mutation, called "modifier genes".
Identification of such modifier genes has been initiated by studying a large family with significant clinical variability in the age of onset of muscle signs. A segregation analysis within this family identified 2 potential modifier loci. High-throughput sequencing restricted to these 2 regions according to phenotypic subgroups did not led to meaningful results so far. In addition, an international retrospective study of the natural history of early muscle laminopathies has allowed the investigators to highlight a strong inter-family clinical variability in patients carrying recurrent mutations. The investigators thus have strong preliminary data that could allow them to identify modifying genetic factors in a cohort of patients carrying a mutation in the LMNA gene.
In order to identify these factors that modulate the clinical severity of laminopathies, the investigators wish to collect biological material (muscle and/or skin biopsies) from patients carrying a mutation in the LMNA gene. The study of this biological material using multi OMICs technics will allow the investigators to identify and functionally validate the action of these modifying genes.
OMIICs is a set of techniques for characterising biological molecules using high-throughput approaches such as DNA sequencing, RNA sequencing and/or chromatin conformation (ATACseq...), proteins.

开始日期2022-09-08

申办/合作机构

Institut National de la Santé et de la Recherche Médicale

NCT01961141

/ WithdrawnN/A

Evaluation of Lung Doppler Signals in Patients With Acute Cardiovascular or Pulmonary Conditions Presenting to the Emergency Medicine Department by a Modified Ultrasound Doppler TCD Device.

Historically, ultrasound has been unable to provide interpretable data from the lung parenchyma, mainly because of the high total ultrasound energy attenuation and scattering by the air in the lungs. Recently it has been shown that clear reproducible Doppler signals can be recorded from the lung parenchyma by means of a pulsed Doppler ultrasound system incorporating a special signal processing package (transthoracic parametric Doppler, TPD, EchoSense Ltd., Haifa, Israel). These lung Doppler signals (LDS) are in full synchrony with the cardiac cycle and can be obtained from the lungs, including areas remote from the heart and main pulmonary vessels. The LDS waves typically have peak velocities of up to 30 cm/s and are of relatively high power, making it possible to detect them despite the aforementioned attenuation by the air in the lungs. The LDS are thought to represent the radial wall movement of small pulmonary blood vessels, caused by pressure pulse waves of cardiac origin which propagate throughout the lung vasculature. The LDS may contain information of significant diagnostic and physiological value regarding the pulmonary parenchyma and vasculature, as well as the cardio-vascular system in general.
Preliminary data from ongoing studies employing the TPD in chronic diseases such as CHF, COPD and pulmonary hypertension, show promise regarding the diagnostic potential of the lung Doppler signals (unpublished data). However, lung Doppler signals in acute disease states were not investigated so far. It is reasonable to speculate that the pathological processes underlying acute cardiovascular and pulmonary diseases will affect the LDS. Therefore, the TPD may have diagnostic potential in these conditions. For example, during acute pulmonary embolism a portion of the pulmonary vascular system is occluded; therefore it's reasonable to assume that the LDS will disappear in the affected area, enabling to confirm the diagnosis without using ionizing radiation (as in CT or lung scan). Another example is COPD exacerbation, during which there is usually air trapping in the lungs; thus, the LDS may be attenuated by the increase of air volume in the lungs.

开始日期2014-11-01

申办/合作机构

Echosense Ltd.

NCT01403402

/ RecruitingN/AIIT

Congenital Muscle Disease Patient and Proxy Reported Outcome Study

The Congenital Muscle Disease Patient and Proxy Reported Outcome Study (CMDPROS) is a longitudinal 10 year study to identify and trend care parameters, adverse events in the congenital muscle diseases using the Congenital Muscle Disease International Registry (CMDIR) to acquire necessary data for adverse event calculations (intake survey and medical records curation). To support this study and become a participant, we ask that you register in the CMDIR. You can do this by visiting www.cmdir.org. There is no travel required.
The registry includes affected individuals with congenital muscular dystrophy, congenital myopathy, and congenital myasthenic syndrome and registers through the late onset spectrum for these disease groups. The CMDIR was created to identify the global congenital muscle disease population for the purpose of raising awareness, standards of care, clinical trials and in the future a treatment or cure. Simply put, we will not be successful in finding a treatment or cure unless we know who the affected individuals are, what the diagnosis is and how the disease is affecting the individual.
Registering in the CMDIR means that you will enter demographic information and complete an intake survey. We would then ask that you provide records regarding the diagnosis and treatment of CMD, including genetic testing, muscle biopsy, pulmonary function testing, sleep studies, clinic visit notes, and hospital discharge summaries.
Study hypothesis:
To use patient and proxy reported survey answers and medical reports to build a longitudinal care and outcomes database across the congenital muscle diseases.
To generate congenital muscle disease subtype specific adverse event rates and correlate with key care parameters.

开始日期2009-09-01

申办/合作机构

Cure CMD

100 项与 Emery-Dreifuss肌营养不良症相关的临床结果

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0 项与 Emery-Dreifuss肌营养不良症相关的专利（医药）

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927

项与 Emery-Dreifuss肌营养不良症相关的文献（医药）

2025-02-01·Neuromuscular Disorders

“Natural history of skeletal muscle laminopathies: a 2-year prospective study”

Article

作者: Zanin, Riccardo ; Ricci, Federica ; Gallone, Annamaria ; Maggi, Lorenzo ; Bonanno, Silvia ; Tramacere, Irene ; Pasanisi, Maria Barbara ; Previtali, Stefano Carlo ; Santovito, Luca Spiro

Skeletal muscle laminopathies (SMLs) are rare disorders characterized by skeletal muscle involvement caused by mutations in LMNA gene. To date, the natural history of SMLs has not been clearly elucidated. Through a 2-year prospective study, we aimed to describe the natural history of SMLs. We enrolled 26 SMLs patients, assessed with: North Star Ambulatory Assessment scale (NSAA), timed tests, manual muscle testing, joint range of motion, six-minutes walking test (6MWT); respiratory evaluation including forced vital capacity (FVC) and forced expiratory volume at 1 second (FEV1); individualized neuromuscular quality of life (INQoL). Muscular performance with the aforementioned tools significantly correlated with phenotypes at the baseline, showing the worse outcome in those with autosomal dominant Emery-Dreifuss muscular dystrophy as compared to limb girdle phenotype. NSAA score significantly (p = 0.0005) worsened during the 2-year follow-up. Moreover, the respiratory function through FVC and FEV1 significantly (p = 0.0086 and p = 0.0290, respectively) deteriorated over the follow-up period. 6MWT, INQoL and timed tests did not significantly change, as well as ankle, knee, and elbow contractures. This study showed a slow progression of motor and respiratory function in SMLs patients over a period of 2 years.

2024-12-01·Stem Cell Research

Generation of a lamin A/C knockout human induced pluripotent stem cell line (ZJULLi007-A) via CRISPR/Cas9

Article

作者: Gong, Tingyu ; Shen, Jiaxi ; Wang, Hao ; Fan, Hangping ; Liu, Dandan ; Yang, Zongkuai ; Liang, Ping

Lamin A/C is a protein encoded by the LMNA gene and belongs to the nuclear lamina protein family. Mutations in the LMNA gene lead to several diseases: Emery-Dreifuss muscular dystrophy, familial partial lipodystrophy, limb girdle muscular dystrophy, dilated cardiomyopathy, Charcot-Marie-Tooth disease, and Hutchinson-Gilford progeria syndrome. In this study, a lamin A/C knockout human induced pluripotent stem cell line was successfully generated using the CRISPR/Cas9 genome-editing technology, which was confirmed with normal pluripotency and karyotype.

2024-12-01·Minerva Pediatrics

Clinical and genetic analysis of Emery-Dreifuss muscular dystrophy type 2 caused by LMNA gene mutation

Article

作者: Yang, Yang

项与 Emery-Dreifuss肌营养不良症相关的新闻（医药）

2023-04-19

·BioSpace

SOLVE FSHD invests in Epic Bio for the development of a novel treatment for Facioscapulohumeral Muscular DystrophyInvestment will further accelerate the development of EPI-321

VANCOUVER, British Columbia, April 18, 2023 (GLOBE NEWSWIRE) -- SOLVE FSHD, a venture-philanthropic organization catalyzing the pace of innovation to accelerate a cure for FSHD, announced today an investment in Epic Bio, a biotechnology company focused on the epigenome of complex diseases. Epic Bio is developing novel therapies that dynamically control gene expression to treat these diseases using compact, non-cutting dCas proteins. This investment will support development of Epic’s lead program EPI-321, a novel therapeutic that is designed to correct the epigenetic alterations in the D4Z4 region of chromosome 4. Epic’s unique approach to correct the molecular pathology implicated in Facioscapulohumeral Muscular Dystrophy (FSHD) should lead to an effective treatment that prevents further muscle degeneration and thereby slows disease progression. “SOLVE FSHD is very pleased to partner with Epic Bio and to add them to our diverse portfolio of companies rapidly moving forward potential therapies for FSHD,” stated Eva Chin, Executive Director of SOLVE FSHD. “SOLVE FSHD identified Epic Bio as a company committed to finding a cure for this debilitating condition and we were impressed by the unique approach that the company is taking to alter the epigenetic cause of the disease. We expect that the support from SOLVE FSHD will allow Epic Bio to rapidly progress EPI-321 into clinical trials.” “Epic Bio welcomes the investment by SOLVE FSHD and we appreciate their important support for the future development of EPI-321,” added Amber Salzman, Chief Executive Officer of Epic Bio. “SOLVE FSHD is rapidly becoming the partner of choice for companies developing FSHD treatments, so their investment provides strong validation of the Epic Bio GEMS platform and the EPI-321 program.” “Today we are very happy to add another company to the SOLVE FSHD portfolio,” noted Chip Wilson, founder and chairman of the Board of SOLVE FSHD. “More importantly, EPI-321 represents another potential treatment for FSHD, a devastating condition that I and many others like me suffer with every day.” Terms of the investment were not disclosed. About Facioscapulohumeral Muscular Dystrophy Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant muscular dystrophy, although thirty percent of new FSHD patients have no prior family history of the disease and result from a congenital spontaneous genetic mutation. FSHD typically first presents with weakness of the muscles of the facial muscles and scapular region, with proximal weakness of the pectoral and abductor muscles limiting upper extremity function at the shoulder girdle. Onset is typically in the teenage and early adult years, but it can present in infancy, which tends to be a more aggressive course. The disease is slowly progressive and approximately 20% of patients are wheelchair bound by age 50. Currently there are no treatments specifically indicated for use in FSHD, with no disease-modifying treatments available. About SOLVE FSHD SOLVE FSHD is a venture philanthropic organization established to catalyze innovation and accelerate key research in finding a cure for FSHD. Established by renowned Canadian entrepreneur and philanthropist Chip Wilson, widely known as the founder of lululemon and part owner of Amer Sports which holds renowned brands such as Arc’teryx, Salomon and Wilson Sports. Chip has committed $100 million to kick-start funding into projects that support the organization’s mission to find a cure for FSHD by 2027. The goal of SOLVE FSHD is to find a solution that can stop muscle degeneration, increase muscle regeneration and strength, and improve the quality of life for those living with FSHD. If you have FSHD and want to find out about clinical trials or be included in the FSHD registry, please see Solve FSHD’s website - About Epic Bio Epic Bio is a leading epigenetic engineering company, leveraging the power of CRISPR without cutting DNA. The company is using its proprietary Gene Expression Modulation System (GEMS) to develop therapies. Through the company’s library of the most compact Cas DNA-binding proteins to work on human cells, the company is developing in vivo therapies with delivery via a single AAV vector. Epic Bio has an initial focus on Facioscapulohumeral Muscular Dystrophy (FSHD) and is conducting additional research to address Antitrypsin Deficiency (A1AD), Heterozygous Familial Hypocholesterolemia (HeFH), as well as other indications. The company is financially backed by Horizons Ventures and other leading investors. Visit for more information or follow us on Twitter and LinkedIn. Media Contact Swati Mehta PR Associates smehta@prassociates.com 403-804-0768

2023-03-09

·生物谷

刘如谦创立，表观遗传编辑公司Chroma完成1.35亿美元B轮融资

基于亓磊实验室的研究成果，Epic Bio公司开发了名为基因表达调控系统（GEMS）的表观遗传工程平台，在不永久改变的DNA的情况下，提高或降低特定基因的表达，从而治疗基因表达失调引起的遗传疾病。在拓展CRISPR基因编辑的应用范围方面，刘如谦（David Liu）是成就最突出的科学家之一。 2016年，刘如谦团队开发了碱基编辑（Base Editing）技术，首次实现了对细胞基因组中的单个碱基进行可靠、可预测的编辑，而且无需DNA双链断裂。2019年，刘如谦团队开发了先导编辑（Prime Editing）技术，同样无需DNA双链断裂，不依赖DNA模板即可有效实现所有12种单碱基的自由转换，而且还能有效实现大片段DNA的精准插入与删除。基于上述研究成果创立的基因编辑公司 Beam Therapeutis 和 Prime Medicine 均已上市。而在2021年，刘如谦创立的 Chroma Medicine 公司宣布完成1.25亿美元的种子轮+A轮融资，开发基于CRISPR的表观遗传编辑技术，并将其应用于疾病治疗。近日，Chroma Medicine 宣布完成1.35亿美元的B轮融资，用于推进表观遗传编辑平台的建设。此次融资规模尤其引人注目，因为过去一段时间生物医药领域股市状态不佳，融资领域也大受影响。2022年第四季度，欧美地区的B轮融资数量创过去三年来历史新低。而此次Chroma的新一轮融资，是2023年迄今为止第七家完成过亿美元融资的公司。 Chroma在表观遗传编辑上充满信心，他们希望在不改变遗传密码本身的情况下调控基因表达。其平台具有持久沉默、激活多重基因的能力。与那些向基因组中插入或删除基因的基因编辑公司相比，表观遗传编辑对脱靶性的担忧更少，这对于安全性和监管要求来说，是一个明显优势。 Chroma公司的表观遗传编辑的模块化平台目前，Chroma公司已完成两轮融资，每轮融资均超过1亿美元，累计融资金额达2.6亿美元。在2021年11月完成1.25亿美元时，Chroma公司当时表示，这些资金将为更多的临床前研究提供资金，并扩大产能。但迄今为止，Chroma公司尚未透露他们具体在做什么，指标是将在今年公布临床前研究数据。据悉，Chroma公司已经积累了一些小鼠研究数据，并计划尽快进行非人灵长类动物实验。其 CEO Catherine Stehman-Breen 透露，Chroma公司已经启动了几个项目，并正在尽快进行人体试验。除了Chroma，近年来还有一些表观遗传编辑公司获得融资。例如Epic Bio、Tune Therapeutis、Omega Therapeutics，以及益杰立科。 2022年7月12日，CRISPR基因编辑先驱亓磊创立的公司 Epic Bio 完成了5500万美元的A轮融资，该公司计划将迷你CRISPR系统（CasMINI）应用于表观遗传编辑，开发出更安全的人类遗传疾病疗法。亓磊，斯坦福大学副教授，1983年出生于山东省潍坊市，本科毕业于清华大学，在加州大学伯克利分校读硕士期间师从诺贝尔物理奖得主朱棣文教授，硕士毕业后，在朱棣文教授的建议下，亓磊从物理学跨专业进入生物工程领域，跟随CRISPR基因编辑先驱、诺贝尔化学奖得主Jennifer Doudna教授研究CRISPR基因编辑。在CRISPR基因编辑领域，亓磊可谓硕果累累，他开发了一些列CRISPR工具，包括用于基因激活和抑制的CRISPRa和CRISPRi，用于DNA和RNA实时成像的LiveFish，用于在三维空间重组基因组的CRISPR-GO，以及小型化CRISPR系统CasMINI，超高效的Cas12a等等。基于亓磊实验室的研究成果，Epic Bio公司开发了名为基因表达调控系统（GEMS）的表观遗传工程平台，在不永久改变的DNA的情况下，提高或降低特定基因的表达，从而治疗基因表达失调引起的遗传疾病。目前，Epic Bio公司公布了5条研发管线，分别是：面肩肱型肌营养不良症（FSHD）、杂合子家族性高胆固醇血症（HeFH）、α-1抗胰蛋白酶缺乏症（A1AD）、色素性视网膜炎4型（RP4）和色素性视网膜炎11型（RP11）。内容来源于网络，如有侵权，请联系删除。

基因疗法核酸药物临床研究

2022-12-23

·生物制品圈

前脚达成7亿美元交易后脚IND就被FDA叫停的Peptide-ASO偶联物

2022年12月19日，Entrada Therapeutics（NASDAQ:TRDA) 宣布其旗下进展最快的Peptide-ASO产品ENTR-601-44的IND申请被FDA叫停。而就在2022年12月8日Entrada临床前资产ENTR-701与Vertex达成超7亿美元的合作。叫停的原因还有待更进一步数据公布，分析可能是由于其宣称的内体逃逸率达到了50%的高精氨酸细胞渗透肽毒性太大导致。 2022年12月8日，Vertex宣布与Entrada Therapeutics（NASDAQ:TRDA) 达成合作协议，引进后者的临床前资产ENTR-701，Vertex支付2.24亿美元预付款，对Entrada进行2600万美元股权投资，并支付4.85亿美元里程碑金额 Entrada Therapeutics（NASDAQ:TRDA) 成立于2016年，总部位于美国马萨诸塞州，是一家致力于利用细胞内生物制剂治疗难治性疾病的生物技术公司。Entrada Therapeutics利用其专有的内体逃逸载体平台EEV，创建并不断扩展寡核苷酸、抗体、酶、蛋白质、肽产品管线，并将治疗范围扩展到神经肌肉疾病以外的其他领域。Entrada Therapeutics创立之初的开发重点是利用多肽将酶递送到胞内的酶替代疗法。后来转向到cyclopeptide-ASO，其技术来源于华人科学家裴德华教授。胞内递送最大的难点就是内体逃逸的问题，递送的药物最大的挑战是在内吞后实现内体逃逸，否则进入溶酶体后ASO会发生降解。 Entrada Therapeutics最大的亮点是内体逃逸率达到了50%左右。即使药物成功穿透细胞，也只有不到 2% 的药物会逃离早期内体到达其预期的细胞内靶点。因此，通常需要高剂量的药物产品才能产生治疗效果，这可能会导致全身性剂量相关毒性。鉴于极高的内体逃逸率，Cyclopeptide作为递送平台应用非常广泛，包括将抗体、酶、寡核苷酸递送到细胞内。EEV平台具有在靶组织中高吸收、高效胞内递送、良好的药效。ENTR-601-44（多肽寡核苷酸偶联物）: 杜氏肌营养不良症（DMD）在DMD发病率1：3500-5000，80%是由于外显子跳跃引起（PS:借用了Dyne的一张DMD发病率的图），Entrada Therapeutics没有选择占比最大的Exon51，而是选择了Exon45（8%）和Exon44（6%）入手。美国发病人数大于12000-15000人，欧洲约25000 人。由于基因突变缺陷导致肌肉细胞不能正常产生一种Dystrophin蛋白，会使钙离子渗入细胞，引发瀑布反应，导致患者全身肌肉无力，又因肌肉细胞内缺少Dystrophin，导致细胞组织肌肉纤维变得无力且脆弱，经长期的伸展后该缺失肌肉细胞组织将产生机械性伤害。ENTR-601-44来处理能观察剂量依赖性dystrophin蛋白产生单次静脉注射ENTR-601-44至少可以持续12周（但没有公布安全性数据）MTD在健康志愿者进行，给药周期初步定为6周（爬坡初始剂量没有公布，如果内体逃逸率这么高，用药剂量还是很值得期待的），预计2022年Q4 IND！ ENTR-701 :1 型强直性肌营养不良症（DM1）强直性肌营养不良症是一种常染色体显性遗传性多系统疾病，特征主要是进行性肌无力、肌萎缩和肌强直。DM1 主要是由强直性肌营养不良蛋白激酶基因（DMPK）变异而导致的肌营养不良。美国发病人数大于40000人，欧洲大于74000 人（PS:还是借用Dyne的一张DM1的图，比较清楚）。在HSA-LR模型中，单剂量ENTR-701显示了至少8周持久疗效。 Entrada Therapeutics 环肽结构 PP1,CPP9,CPP12 胞浆递送效率分别为20%，62%，120%，而TAT仅为2%。环化、精氨酸、奈基丙氨酸、其它疏水氨基酸是高效进入细胞的特征根据其专利，基本都是环肽（单环、双环都有）+奈基丙氨酸+精氨酸的组合，高渗透性。总结细胞渗透肽作为寡核苷酸的递药载体，具有以下优点：1：相对抗体递送，分子量小用药剂量小2：具有很高的内体逃逸率，大大提高药效降低剂量但高精氨酸细胞渗透肽作为递送系统缺点也显而易见，可能存在极大的溶血毒性！内容来源于网络，如有侵权，请联系删除。

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