Neuromuscular Disorders最新文献

Potential relationship between MuSK-MG and autologous hematopoietic stem cell transplantation: a case report 麝香- mg与自体造血干细胞移植的潜在关系1例

IF 2.7 4区医学

Neuromuscular Disorders Pub Date : 2025-07-08 DOI: 10.1016/j.nmd.2025.105444

Ryo Sasaki , Ryoma Nakamura , Yoshiaki Takahashi , Mizuki Morimoto , Yukiko Kubo , Nobutoshi Morimoto

{"title":"Potential relationship between MuSK-MG and autologous hematopoietic stem cell transplantation: a case report","authors":"Ryo Sasaki , Ryoma Nakamura , Yoshiaki Takahashi , Mizuki Morimoto , Yukiko Kubo , Nobutoshi Morimoto","doi":"10.1016/j.nmd.2025.105444","DOIUrl":"10.1016/j.nmd.2025.105444","url":null,"abstract":"<div><div>A 61-year-old woman developed anti-muscle-specific tyrosine kinase antibody positive myasthenia gravis (MuSK-MG) three years after autologous hematopoietic stem cell transplantation (HSCT) for multiple myeloma. Symptoms improved following methylprednisolone pulse therapy, intravenous immunoglobulin, plasma exchange, and the addition of efgartigimod. A review of the literature revealed that all four previously reported cases of myasthenia gravis after autologous HSCT were MuSK-MG, although none were positive for anti-acetylcholine receptor (AChR) antibodies. This frequency differs significantly from the reported incidence of MuSK-MG in the general population and in patients following allogeneic HSCT, suggesting a potential association between autologous HSCT and MuSK-MG. Hypothesized mechanisms include a paraneoplastic mechanism and changes of IgG4 production following immune reconstitution after autologous HSCT. We suggest that clinicians should be aware of this possibility and consider MuSK-MG in the differential diagnosis of neurological symptoms that arise after autologous HSCT, even though autologous HSCT can be used as a therapeutic option for MuSK-MG.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105444"},"PeriodicalIF":2.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144631963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sarcoid neuropathy exhibiting intraneural nodule with central hypointensity on short-tau inversion recovery imaging: a heron-like appearance 结节性神经病变表现为神经内结节，短tau倒置恢复成像显示中心低密度：鹭样外观

IF 2.7 4区医学

Neuromuscular Disorders Pub Date : 2025-07-05 DOI: 10.1016/j.nmd.2025.105438

Yuki Nakagawa, Atsuhiko Sugiyama, Manato Yasuda, Satoshi Kuwabara

引用次数: 0

Hypokalemic periodic paralysis associated with the atypical CACNA1S c.2690G>A (p.Arg897Lys) variant: description of 14 affected individuals from five families 低钾性周期性麻痹与非典型CACNA1S c.2690G>A （p.a g897lys）变异相关：来自5个家族的14名受影响个体的描述

IF 2.7 4区医学

Neuromuscular Disorders Pub Date : 2025-07-02 DOI: 10.1016/j.nmd.2025.105425

Oriol Barrachina-Esteve , Marc Ventayol-Guirado , Victor J Asensio , Damià Heine-Suñer , Ricardo Corrales , Noemí Vidal , Trajche Ivanovski , Clara Arbós , Maite Agirre , Carles Montalà , Jordi Ballabriga , Ana Valero , M Magdalena Rosselló , Pablo Dávila , Margalida Mestre , Ana Sánchez , Elena Deyá , Inés Legarda , Ana Espino , Montse Olivé , Francesc Miralles

{"title":"Hypokalemic periodic paralysis associated with the atypical CACNA1S c.2690G>A (p.Arg897Lys) variant: description of 14 affected individuals from five families","authors":"Oriol Barrachina-Esteve , Marc Ventayol-Guirado , Victor J Asensio , Damià Heine-Suñer , Ricardo Corrales , Noemí Vidal , Trajche Ivanovski , Clara Arbós , Maite Agirre , Carles Montalà , Jordi Ballabriga , Ana Valero , M Magdalena Rosselló , Pablo Dávila , Margalida Mestre , Ana Sánchez , Elena Deyá , Inés Legarda , Ana Espino , Montse Olivé , Francesc Miralles","doi":"10.1016/j.nmd.2025.105425","DOIUrl":"10.1016/j.nmd.2025.105425","url":null,"abstract":"<div><div>This study describes five families (14 individuals) with hypokalemic periodic paralysis carrying a heterozygous pathogenic variant NM_000069.3:c.2690G>A (p.Arg897Lys) in the Calcium Voltage-Gated Channel Subunit Alpha1 S (<em>CACNA1S</em>) gene. The clinical exam showed pelvic weakness was common (10/14, with three being too young to exclude this age-dependent myopathy). Electromyography showed myogenic changes, and the long exercise test did not reveal a significant reduction of compound muscle action potential amplitude. Muscle MRI in three patients demonstrated involvement of axial musculature, the pelvic girdle, thighs (with relative sparing of sartorius and gracilis), and legs (especially the gastrocnemius muscles). A homozygosity haplotype analysis in three families revealed a shared segment of approximately 10 million base pairs, suggesting a common ancestor 2-8 generations ago.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105425"},"PeriodicalIF":2.7,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144597403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The recent clinical trial of losmapimod for the treatment of facioscapulohumeral muscular dystrophy losmapimod治疗面肩肱肌营养不良症的最新临床试验

IF 2.7 4区医学

Neuromuscular Disorders Pub Date : 2025-06-22 DOI: 10.1016/j.nmd.2025.105422

Robert J. Bloch , Maria Traficante , Virginie Mariot , Julie Dumonceaux

{"title":"The recent clinical trial of losmapimod for the treatment of facioscapulohumeral muscular dystrophy","authors":"Robert J. Bloch , Maria Traficante , Virginie Mariot , Julie Dumonceaux","doi":"10.1016/j.nmd.2025.105422","DOIUrl":"10.1016/j.nmd.2025.105422","url":null,"abstract":"<div><div>Facioscapulohumeral muscular dystrophy is a progressive muscle disorder that is likely linked to aberrant DUX4 expression. Losmapimod, a p38 kinase inhibitor, was utilized to suppress DUX4 and its downstream effects. Phase I/II clinical trials showed promising functional improvements in muscle strength and reachable workspace, despite showing no significant reduction in DUX4-driven gene expression. Based on these findings, a larger phase III trial was conducted, prioritizing functional outcomes. However, the trial failed to demonstrate a clear clinical benefit, highlighting key challenges in drug development for the disease. Notably, the underlying mechanism by which p38K inhibition affects DUX4 in mature muscle remains poorly understood, and most preclinical studies with losmapimod were performed <em>in vitro</em> on immature muscle cells. This raises concerns about the relevance of <em>in vitro</em> models for drug testing. The failure of losmapimod underscores the need for better disease models, such as xenografts, and a deeper understanding of DUX4 regulation, before advancing future therapies to clinical trials.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"52 ","pages":"Article 105422"},"PeriodicalIF":2.7,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144490013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Levels of exercise exposure among people living with neuromuscular disorders: lessons learned from real-world data 神经肌肉疾病患者的运动暴露水平：来自现实世界数据的经验教训

IF 2.7 4区医学

Neuromuscular Disorders Pub Date : 2025-06-16 DOI: 10.1016/j.nmd.2025.105421

Mark Richardson , Virginie Kinet , Karen Wong , Maha Elseed , Dionne Moat , Elizabeth Harris , Jassi Michel-Sodhi , Carla Bolano-Diaz , Michelle McCallum , Emma Robinson , Marianela Schiava , Emma Grover , Doaa Salman , Michela Guglieri , Giorgio Tasca , Elisabetta Ghimenton , Jordi Diaz-Manera , Anna Mayhew , Meredith K. James , Volker Straub , Robert Muni-Lofra

{"title":"Levels of exercise exposure among people living with neuromuscular disorders: lessons learned from real-world data","authors":"Mark Richardson , Virginie Kinet , Karen Wong , Maha Elseed , Dionne Moat , Elizabeth Harris , Jassi Michel-Sodhi , Carla Bolano-Diaz , Michelle McCallum , Emma Robinson , Marianela Schiava , Emma Grover , Doaa Salman , Michela Guglieri , Giorgio Tasca , Elisabetta Ghimenton , Jordi Diaz-Manera , Anna Mayhew , Meredith K. James , Volker Straub , Robert Muni-Lofra","doi":"10.1016/j.nmd.2025.105421","DOIUrl":"10.1016/j.nmd.2025.105421","url":null,"abstract":"<div><div>There is growing evidence on safety and efficacy of exercise in neuromuscular diseases. We sought to establish the levels of exercise exposure for people living with NMD and its association with mobility levels and pain. A standardized questionnaire was used during clinical follow up consultations to categorise exposure to aerobic, strengthening and stretching exercise for 830 patients with 41 different NMD. The level of exercise exposure of people living with NMD in each type of exercise has been found to be limited and the proportion of patient being complying with WHO physical activity guidelines (8 %) was lower than previously reported. Stretching exercise was the most performed type of exercise (37 %), while resistance exercise was the least performed type of exercise (25 %) with aerobic exercise being performed by 33 %. Associations were found between exercise type and diagnosis, mobility status and pain all using chi square testing with significance level of less than 1 %. Patients with greater levels of mobility were more likely to participate in aerobic and resistance exercise and less likely to participate in stretching exercise. The presence of pain was associated with lack of participation in aerobic and resistance exercise but not stretching exercise. Levels of mobility and presence of pain have been identified as significant factors. It is critical to improve supported access and specific exercise guidelines for people living with NMD.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"52 ","pages":"Article 105421"},"PeriodicalIF":2.7,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Distinguishing immune checkpoint inhibitor-induced hypothyroid myopathy from myositis: a case report and review 区分免疫检查点抑制剂诱导的甲状腺功能减退与肌炎：1例报告和回顾

IF 2.7 4区医学

Neuromuscular Disorders Pub Date : 2025-06-16 DOI: 10.1016/j.nmd.2025.105420

Nozomu Tawara , Mina Itasaka , Yuko Horio , Kazuaki Sugahara , Kentaro Hara , Chikako Nagatoshi , Akiko Fujimoto , Masatoshi Ishizaki , Ryoichi Kurisaki , Yasuto Nisida , Kazuyoshi Nakamura , Yasushi Maeda , Mitsuharu Ueda , Hidetsugu Ueyama

{"title":"Distinguishing immune checkpoint inhibitor-induced hypothyroid myopathy from myositis: a case report and review","authors":"Nozomu Tawara , Mina Itasaka , Yuko Horio , Kazuaki Sugahara , Kentaro Hara , Chikako Nagatoshi , Akiko Fujimoto , Masatoshi Ishizaki , Ryoichi Kurisaki , Yasuto Nisida , Kazuyoshi Nakamura , Yasushi Maeda , Mitsuharu Ueda , Hidetsugu Ueyama","doi":"10.1016/j.nmd.2025.105420","DOIUrl":"10.1016/j.nmd.2025.105420","url":null,"abstract":"<div><div>Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment; however, they can induce immune-related adverse events (irAEs), including hypothyroidism, the most common endocrine irAE. ICI-induced hypothyroid myopathy (ir-HM) is a rare condition that can be mistaken for ICI-induced myositis (ir-myositis). We encountered a case of ir-HM that was similar to ir-myositis. A 72-year-old male with lung cancer developed hypothyroidism and myopathy 21 weeks after initiating pembrolizumab treatment. Muscle biopsy revealed myofibrillar network disruption without inflammatory changes. A literature review identified 9 ir-HM cases, typically occurring more than 2 months after the initiation of ICI therapy. Key distinctions between ir-HM and ir-myositis include onset time, treatment approach, and the presence of the myoedema. Proper diagnosis of ir-HM is crucial for appropriate management, potentially allowing continuation of ICI therapy. This study highlights the importance of considering ir-HM in patients with myopathy symptoms occurring a longer period after the initiation of ICI treatment.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"52 ","pages":"Article 105420"},"PeriodicalIF":2.7,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An HTLV-1 carrier with sporadic late-onset nemaline myopathy accompanied by skin lesions indicating indolent adult T-cell leukemia/lymphoma and Sjögren’s syndrome: a case report and literature review HTLV-1携带者，散发迟发性线状肌病伴皮肤病变，提示成人惰性t细胞白血病/淋巴瘤和Sjögren综合征：1例报告和文献复习

IF 2.7 4区医学

Neuromuscular Disorders Pub Date : 2025-06-13 DOI: 10.1016/j.nmd.2025.105417

Ako Miyata , Tomomi Shijo , Rumiko Izumi , Emi Yamazaki , Naoto Sugeno , Naoki Suzuki , Ichizo Nishino , Yoshihide Asano , Masashi Aoki

{"title":"An HTLV-1 carrier with sporadic late-onset nemaline myopathy accompanied by skin lesions indicating indolent adult T-cell leukemia/lymphoma and Sjögren’s syndrome: a case report and literature review","authors":"Ako Miyata , Tomomi Shijo , Rumiko Izumi , Emi Yamazaki , Naoto Sugeno , Naoki Suzuki , Ichizo Nishino , Yoshihide Asano , Masashi Aoki","doi":"10.1016/j.nmd.2025.105417","DOIUrl":"10.1016/j.nmd.2025.105417","url":null,"abstract":"<div><div>Sporadic late-onset nemaline myopathy (SLONM) is a rare acquired myopathy. Herein, we report a rare case of co-occurring SLONM, indolent adult T-cell leukemia/lymphoma (ATL), and Sjögren’s syndrome (SS) in a 60-year-old woman who was a human T-cell leukemia virus type 1 (HTLV-1) carrier. She presented with sub-acute proximal muscle weakness and chest erythema. Muscle biopsy revealed perivascular inflammation and accumulation of nemaline bodies in the atrophic fibers. Skin biopsy indicated indolent ATL. Analysis of specific antibodies and salivary gland biopsy led to a SS diagnosis. CD4-positive T cells expressing FoxP3 and CCR4, which constitute an HTLV-1-infected cell signature, were observed in all three tissues. Her muscular and cutaneous symptoms responded well to steroids. This case suggests a potential link between HTLV-1 latent infection and reactivation and SLONM development and progression. We review the clinicopathological features of SLONM across various etiologies, providing valuable insights into this rare condition.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"52 ","pages":"Article 105417"},"PeriodicalIF":2.7,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144322839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Like father, like son: RNA-sequencing from a 30-year-old muscle biopsy identifies a novel splice variant in ACTA1 as the cause of an attenuated nemaline myopathy phenotype 有其父必有其子：来自30岁肌肉活检的rna测序确定了ACTA1中一种新的剪接变体是弱线状肌病表型的原因

IF 2.7 4区医学

Neuromuscular Disorders Pub Date : 2025-06-04 DOI: 10.1016/j.nmd.2025.105416

Alayne P. Meyer , Sana Yousfi , Stefan Nicolau , Afrooz Rashnonejad , Jingting Zhu , Zarife Sahenk , Emma Frair , Hui Lin , Swetha Ramadesikan , Daniel Koboldt , Kevin M. Flanigan

{"title":"Like father, like son: RNA-sequencing from a 30-year-old muscle biopsy identifies a novel splice variant in ACTA1 as the cause of an attenuated nemaline myopathy phenotype","authors":"Alayne P. Meyer , Sana Yousfi , Stefan Nicolau , Afrooz Rashnonejad , Jingting Zhu , Zarife Sahenk , Emma Frair , Hui Lin , Swetha Ramadesikan , Daniel Koboldt , Kevin M. Flanigan","doi":"10.1016/j.nmd.2025.105416","DOIUrl":"10.1016/j.nmd.2025.105416","url":null,"abstract":"<div><div><em>ACTA1</em>-related nemaline myopathy is a disorder typically presenting in the neonatal period, but later-onset cases have been described. The majority of patients carry <em>de novo</em> missense variants. We report a father and son with shared features of early-onset, but mild myopathic symptoms, including gross motor delay and facial weakness. Muscle biopsies showed nemaline rods. Genetic testing identified a novel splice variant in <em>ACTA1</em> (c.809–10C><em>A</em>). RNA-sequencing was performed on muscle, including the father’s sample which had been archived for 31 years; both showed retention of intron 5 in ∼20 % of transcripts, predicted to cause protein truncation, but not nonsense mediated decay. <em>In vitro</em> studies showed that the variant leads to the formation of ACTA1 aggregates. These findings provide functional support for the variant’s pathogenicity in dominantly inherited nemaline myopathy and rationale for the attenuated phenotype. This case highlights the utility of muscle biopsy and RNA-sequencing in the diagnosis of nemaline myopathy.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"52 ","pages":"Article 105416"},"PeriodicalIF":2.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144490014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multi-omics approach identifies a novel recessive pathogenic variant in the TNNT3 gene in two siblings with congenital myopathy 多组学方法鉴定了两个患有先天性肌病的兄弟姐妹中TNNT3基因的一种新的隐性致病变异

IF 2.7 4区医学

Neuromuscular Disorders Pub Date : 2025-06-03 DOI: 10.1016/j.nmd.2025.105415

Juliane S. Müller , Shira Rabinowicz , Irina Zaharieva , Veronica Pini , Vicente A. Yépez , Anna Esteve-Codina , Darren Chambers , Andrew Dawson , Luke Perry , Brian Herron , Estelle Healy , Sandya Tirupathi , Ana Töpf , Stephanie DiTroia , Rahul Phadke , Francesco Muntoni , Anna Sarkozy

{"title":"Multi-omics approach identifies a novel recessive pathogenic variant in the TNNT3 gene in two siblings with congenital myopathy","authors":"Juliane S. Müller , Shira Rabinowicz , Irina Zaharieva , Veronica Pini , Vicente A. Yépez , Anna Esteve-Codina , Darren Chambers , Andrew Dawson , Luke Perry , Brian Herron , Estelle Healy , Sandya Tirupathi , Ana Töpf , Stephanie DiTroia , Rahul Phadke , Francesco Muntoni , Anna Sarkozy","doi":"10.1016/j.nmd.2025.105415","DOIUrl":"10.1016/j.nmd.2025.105415","url":null,"abstract":"<div><div>TNNT3 is the fast skeletal muscle troponin T compound of the troponin complex. Dominantly inherited pathogenic missense variants in <em>TNNT3</em> cause distal arthrogryposis, whereas rare recessive <em>TNNT3</em> variants are associated with congenital myopathy with distal arthrogryposis with and without nemaline rods. Here, we report two teenage sisters who presented at birth with hypotonia, proximal weakness, feeding difficulties and finger contractures. Muscle weakness was not progressive and clinical function improved over time. Muscle biopsies showed small atrophic fast fibres, internal nuclei, increased connective tissue and focal fat infiltration. Ultrastructural investigation revealed disorganised myofibrils and nemaline bodies in some fibres. Targeted sequencing of panel of genes causing congenital myopathy was negative. Trio whole exome and genome sequencing identified a novel homozygous intronic <em>TNNT3</em> variant, c.67+128G><em>A</em>. Sequencing of RNA derived from the patient’s muscle confirmed the variant’s detrimental effect on splicing. This work expands the allelic spectrum of <em>TNNT3</em> related congenital myopathy and confirms the previously reported favourable disease course in some patients, although with an overall milder disease presentation in both siblings. It also highlights the utility of a combined multi-omics approach to diagnose previously unsolved cases of congenital myopathy.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"52 ","pages":"Article 105415"},"PeriodicalIF":2.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144338901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Antisense oligonucleotide-mediated redirection of Igf1 alternative polyadenylation 反义寡核苷酸介导的Igf1选择性聚腺苷化重定向。

IF 2.7 4区医学

Neuromuscular Disorders Pub Date : 2025-06-01 DOI: 10.1016/j.nmd.2025.105394

Alper Yavas, Maaike van Putten, Yavuz Ariyurek, Annemieke Aartsma-Rus

{"title":"Antisense oligonucleotide-mediated redirection of Igf1 alternative polyadenylation","authors":"Alper Yavas, Maaike van Putten, Yavuz Ariyurek, Annemieke Aartsma-Rus","doi":"10.1016/j.nmd.2025.105394","DOIUrl":"10.1016/j.nmd.2025.105394","url":null,"abstract":"<div><div>Insulin-like growth factor-1 (IGF-1) has become an interesting potential therapeutic target for muscle wasting disorders, since it is known to modulate muscle growth and function. Alternative polyadenylation (APA) <em>Igf1</em> gives rise to 3′UTR isoforms with different stability and translation efficiency due to their length and context-dependent miRNA binding sites. <em>Igf1</em> transcripts with a shorter 3′UTRs are thought to be more stable and efficient during protein translation. Therefore, modulating the <em>Igf1</em> polyadenylation site usage would be a potential approach to increase IGF-1 protein expression. In this study, we first investigated the <em>Igf1</em> 3′UTR isoforms in exercised <em>mdx</em> and WT mice by full-length isoform sequencing. We then redirected the APA of <em>Igf1</em> from the distal to the proximal/middle polyadenylation sites to enhance the IGF-1 protein expression in mouse C2C12 myoblasts. Upon exercise, APA of <em>Igf1</em> was redirected towards the proximal polyadenylation site in the WT mice only (<em>P</em> < 0.05). Transfection of C2C12 cells with this AON resulted in redirection of the APA towards the proximal site and increased IGF-1 expression/AKT phosphorylation levels. Strong enrichment was found for genes involved in sarcomere organization, muscle cell development and calcium homeostasis. Our study reports the effect of downhill running exercise on the <em>Igf1</em> 3′UTRs in <em>mdx</em> and WT mice and provides an <em>in vitro</em> proof of principle for redirecting the <em>Igf1</em> poly(A) site usage as a strategy to increase protein expression without modifying the coding region of the gene, not only for IGF-1 but also for other targets with therapeutic potential in different conditions.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"51 ","pages":"Article 105394"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0