Annals of Clinical and Translational Neurology最新文献

{"title":"Phase 1, First-In-Human, Single-/Multiple-Ascending Dose Study of Iluzanebart in Healthy Volunteers.","authors":"Andreas Meier, Spyros Papapetropoulos, Andrew Marsh, Kelly Neelon, David Stiles, Ryan O'Mara, Evan A Thackaberry, Marco Colonna, Raj Rajagovindan","doi":"10.1002/acn3.70033","DOIUrl":"https://doi.org/10.1002/acn3.70033","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of iluzanebart, a fully human monoclonal antibody TREM2 (triggering receptor expressed on myeloid cells 2) agonist, after single- (SAD) and multiple-ascending-dose (MAD) administration.</p><p><strong>Methods: </strong>Healthy adult volunteers (N = 136) received intravenous placebo or iluzanebart 1-60 mg/kg (SAD) or 10-60 mg/kg (MAD) followed by serial pharmacokinetics and safety assessments. Safety assessments included adverse events (AEs), vital signs, electrocardiograms, and clinical laboratory evaluations. Pharmacokinetics were assessed through noncompartmental analysis. The study also included open-label cohorts (3, 10, 20, 40, 60 mg/kg SAD; 10, 20, 40 mg/kg MAD) for cerebrospinal fluid (CSF) collection for exploratory pharmacodynamic biomarker analysis.</p><p><strong>Results: </strong>Iluzanebart was safe and well tolerated following single and multiple doses of up to 60 mg/kg. Most AEs were mild and resolved spontaneously. The most frequently reported AE was pruritus. No serious AEs or investigational product-related clinically meaningful changes in vital signs, electrocardiograms, or laboratory assessments were reported. Iluzanebart serum exposure was related to dose, with a 29-day half-life that is supportive of monthly dosing and confirmed central nervous system (CNS) exposure (≈0.15% CSF-to-serum ratio). Durable and dose-dependent target engagement, evidenced by marked reductions in soluble TREM2 and increased soluble CSF1R (colony-stimulating factor 1 receptor) and osteopontin/SPP1 (secreted phosphoprotein 1) levels in CSF, was observed, indicating that iluzanebart changes microglial activity following single and repeat dosing.</p><p><strong>Interpretation: </strong>Iluzanebart demonstrated favorable safety, tolerability, pharmacokinetics, and pharmacological activity in the CNS, supporting further clinical development for adult-onset leukoencephalopathy with axonal spheroids and pigmented glia.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reconstitution of CXCR3⁺ CCR6⁺ Th17.1-Like T Cells in Response to Ofatumumab Therapy in Patients With Multiple Sclerosis.","authors":"Shu Yang, Tian-Xiang Zhang, Jia Liu, Zhirui Liu, Lijie Zhu, Yan-Yan Li, Bin Feng, Moli Fan, Fu-Dong Shi, Chao Zhang","doi":"10.1002/acn3.70042","DOIUrl":"https://doi.org/10.1002/acn3.70042","url":null,"abstract":"<p><strong>Background and objectives: </strong>Ofatumumab, a fully human anti-CD20 monoclonal antibody, is effective in reducing relapses and disability progression in patients with multiple sclerosis. This study aimed to examine immune profile changes associated with ofatumumab in a prospective cohort of Chinese patients with relapsing-remitting multiple sclerosis (RRMS).</p><p><strong>Methods: </strong>Seventeen RRMS patients were enrolled in this uncontrolled, prospective, observational cohort study (OMNISCIENCE study) and received regular subcutaneous ofatumumab treatments. Immune cell subsets were analyzed by single-cell mass cytometry at baseline and 6 months post-treatment. Peripheral blood monoclonal cells (PBMCs) from a separate cohort of treatment-naive RRMS patients were used for cytokine analysis through ex vivo flow cytometry.</p><p><strong>Results: </strong>Following ofatumumab treatment, B cells in peripheral blood remained depleted, with surviving cells predominantly consisting of antibody-secreting cells and transitional B cells. Increased proportions of NK cells and myeloid cells, particularly HLA-DR^hi intermediate monocytes, were observed, and FOXP3 and CTLA-4 expression on CD4⁺ T cells was upregulated. Notably, prior to the subsequent dose of ofatumumab, Th17.1-like CXCR3⁺CCR6⁺ memory CD4⁺ and CD8⁺ T cell clusters increased significantly, with a transient CD20 expression rebound. In vitro experiments further confirmed that ofatumumab reduced these Th17.1 cell subsets and related pro-inflammatory cytokines.</p><p><strong>Discussion: </strong>These findings suggest that ofatumumab impacts interactions among pathogenic B cells, T cells, and myeloid cells, with Th17.1 cells emerging as a potential direct target within T cells. Persistent and regular infusions of ofatumumab appear necessary to sustain clinical efficacy.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT05414487.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CSF Tau Is a Biomarker of Hippocampal Injury in Cryptogenic New-Onset Refractory Status Epilepticus.","authors":"Yihui Goh, Yoonhyuk Jang, Soo Jean Shin, Soo Hyun Ahn, Su Yee Mon, Yoon Hee Shin, Kon Chu, Sang Kun Lee, Soon-Tae Lee","doi":"10.1002/acn3.70043","DOIUrl":"https://doi.org/10.1002/acn3.70043","url":null,"abstract":"<p><strong>Objective: </strong>Cryptogenic new-onset refractory status epilepticus (cNORSE) is a devastating condition characterized by the de novo onset of status epilepticus with unclear etiology. The identification of relevant early biomarkers in cNORSE is important to elucidate pathophysiology, aid clinical decision-making, and prognosticate outcomes in cNORSE.</p><p><strong>Methods: </strong>CSF samples were obtained within 7 days of NORSE onset from an adult cNORSE cohort in a national referral center in South Korea. Nineteen patients with cNORSE were studied: 9 were male (47.4%) and the median age was 35.0 [IQR: 27.0-54.3] years. CSF from 21 patients with other neurological diseases (atypical parkinsonism, postural orthostatic hypotension syndrome, epilepsy, and cerebellar ataxia) was used as controls. Proteomic analysis was conducted using the Olink platform, and potential biomarker candidates were correlated with clinical data and MRI findings.</p><p><strong>Results: </strong>Based on correlation analyses between proteomic data and clinical outcomes, total tau (t-tau) was selected as a potential biomarker. Patients with cNORSE had higher CSF t-tau levels than controls (p < 0.001). Early detection of high CSF t-tau was associated with the presence of hippocampal atrophy in the postacute phase of cNORSE (p = 0.044). The initial elevation of t-tau levels also correlated with a higher number of anti-seizure medications used (p = 0.031) and less improvement in Clinical Assessment Scale in Autoimmune Encephalitis (CASE) scores 1 month after NORSE onset (p = 0.066). T-tau levels were correlated with CSF pro-inflammatory cytokines/chemokines and mediators of neuronal damage.</p><p><strong>Interpretation: </strong>Elevated CSF t-tau levels detected early after cNORSE onset may be a useful marker of initial brain injury and predict subsequent hippocampal atrophy.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Phenotypes and Deep Intronic Variant Expand TH-Associated Dopa-Responsive Dystonia Spectrum.","authors":"Xiaosheng Zheng, Chenxin Ying, Nan Jin, Jinghong Ma, Xinhua Wan, Xunhua Li, Wei Luo","doi":"10.1002/acn3.70013","DOIUrl":"https://doi.org/10.1002/acn3.70013","url":null,"abstract":"<p><p>Approximately 20% of dopa-responsive dystonia (DRD) cases remain genetically unresolved. Using whole-genome sequencing, we identified two TH variants in a young DRD patient, including a novel deep intronic variant. Minigene assays confirmed that this variant causes aberrant splicing. The patient exhibited an atypical disease progression compared with typical TH-associated DRD cases, presenting with generalized dystonia, episodic hypotonia, Parkinsonism, and oromandibular dyskinesias. These findings, including the first known documented deep intronic TH variant, expand our understanding of TH-associated DRD's phenotypic and genotypic spectrum, aiding clinical evaluation.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Case of a 67-Year-Old Man With Memory Difficulties and Altered Sleep.","authors":"Wesley Peng, Borna Bonakdarpour","doi":"10.1002/acn3.70027","DOIUrl":"https://doi.org/10.1002/acn3.70027","url":null,"abstract":"","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epitope Mapping of Anti-Neurofascin 155 Antibody in a Large Cohort of Autoimmune Nodopathy Patients.","authors":"Amina A Abdelhadi, Hidenori Ogata, Xu Zhang, Takumi Tashiro, Ryo Yamasaki, Jun-Ichi Kira, Noriko Isobe","doi":"10.1002/acn3.70036","DOIUrl":"https://doi.org/10.1002/acn3.70036","url":null,"abstract":"<p><strong>Objective: </strong>Autoimmune nodopathy (AN), a newly recognized disease entity, is an immune-mediated polyneuropathy involving autoantibodies against cell adhesion molecules located in nodes of Ranvier and paranodal regions, such as neurofascin 186 (NF186) and neurofascin 155 (NF155). The present study aimed to identify the epitopes for autoantibodies against NF155 in a large cohort of Japanese patients with anti-NF155 antibody-positive (anti-NF155+) AN.</p><p><strong>Methods: </strong>Human embryonic kidney 293 cells stably expressing NF155, NF186, or the third to fourth fibronectin type III domain region (Fn3-Fn4) of NF155, as well as cells transiently expressing Fn3, Fn4, or the shorter Fn3-Fn4 region of NF155, were developed. Western blotting and flow cytometric cell-based assay (CBA) analyses were performed to determine the expression levels of the proteins and identify their target epitopes in serum samples from 100 IgG4 anti-NF155+ patients, four non-IgG4 anti-NF155+ patients, and eight healthy controls.</p><p><strong>Results: </strong>The expression levels of NF186, NF155, Fn3-Fn4 of NF155, and the other truncation variants of NF155 were confirmed by western blotting and flow cytometric CBA. Flow cytometric CBA analysis showed that the autoantibodies in all 104 anti-NF155+ patients bound to Fn3-Fn4. No autoantibodies reacted with NF186, Fn4, or shorter Fn3-Fn4, although the autoantibodies in one IgG4 anti-NF155+ patient (1.0%) recognized Fn3 in addition to Fn3-Fn4. Western blotting analysis of representative samples generally reproduced the CBA results.</p><p><strong>Interpretation: </strong>The present study involving a large cohort of patients clarified that the primary epitope for anti-NF155 antibodies is located in the Fn3-Fn4 region, but not in the Fn3 or Fn4 domains alone.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unleashing the Power of Multiomics: Unraveling the Molecular Landscape of Peripheral Neuropathy.","authors":"Julie Choi, Zitian Tang, Wendy Dong, Jenna Ulibarri, Elvisa Mehinovic, Simone Thomas, Ahmet Höke, Sheng Chih Jin","doi":"10.1002/acn3.70019","DOIUrl":"10.1002/acn3.70019","url":null,"abstract":"<p><p>Peripheral neuropathies (PNs) affect over 20 million individuals in the United States, manifesting as a wide range of sensory, motor, and autonomic nerve symptoms. While various conditions such as diabetes, metabolic disorders, trauma, autoimmune disease, and chemotherapy-induced neurotoxicity have been linked to PN, approximately one-third of PN cases remain idiopathic, underscoring a critical gap in our understanding of these disorders. Over the years, considerable efforts have focused on unraveling the complex molecular pathways underlying PN to advance diagnosis and treatment. Traditional methods such as linkage analysis, fluorescence in situ hybridization, polymerase chain reaction, and Sanger sequencing identified initial genetic variants associated with PN. However, the establishment and application of next-generation sequencing (NGS) and, more recently, long-read/single-cell sequencing have revolutionized the field, accelerating the discovery of novel disease-causing variants and challenging previous assumptions about pathogenicity. This review traces the evolution of genomic technologies in PN research, emphasizing the pivotal role of NGS in uncovering genetic complexities. We provide a comprehensive analysis of established genomic approaches such as genome-wide association studies, targeted gene panel sequencing, and whole-exome/genome sequencing, alongside emerging multiomic technologies including RNA sequencing and proteomics. Integrating these approaches promises holistic insights into PN pathophysiology, potentially revealing new biomarkers and therapeutic targets. Furthermore, we discuss the clinical implications of genomic and multiomic integration, highlighting their potential to enhance diagnostic accuracy, prognostic assessment, and personalized treatment strategies for PN. Challenges and questions in standardizing these technologies for clinical use are raised, underscoring the need for robust guidelines to maximize their clinical utility.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Home-Based Tele-tDCS in Amyotrophic Lateral Sclerosis: Feasibility, Safety, and Preliminary Efficacy.","authors":"Sangeetha Madhavan, Shravni Deshmukh, Mark Cummings, Aditi Doshi, Kourosh Rezania, Sally Freels, Gina Sawa","doi":"10.1002/acn3.70038","DOIUrl":"https://doi.org/10.1002/acn3.70038","url":null,"abstract":"<p><strong>Objective: </strong>Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with limited treatment options. Transcranial direct current stimulation (tDCS) shows promise as a neuromodulatory intervention in various neurological disorders, but its application in ALS, particularly in a remote, home-based format, remains underexplored. This study investigates the feasibility, safety, and preliminary efficacy of remotely supervised tele-tDCS in ALS patients.</p><p><strong>Methods: </strong>This double-blinded pilot study included 14 spinal-onset ALS participants randomized into two groups: the intervention group received 72 tele-tDCS sessions over 24 weeks, and the delayed-start group received 36 sham sessions followed by 36 tele-tDCS sessions. Stimulation was delivered at 2 mA for 20 min 3 times a week. Primary outcomes included feasibility, safety, and disease progression measured by the ALS Functional Rating Scale-Revised (ALSFRS-R). Adherence and adverse effects were monitored throughout.</p><p><strong>Results: </strong>Ten participants completed the study, with an overall compliance rate of 98.3%. No serious adverse events were reported, and mild side effects, like itching and tingling, were consistent with tDCS literature. The intervention group demonstrated a significantly slower decline in ALSFRS-R scores than the delayed-start group. At 24 weeks, the intervention group had a mean ALSFRS-R change of -1.7, compared to -13.6 in the delayed-start group (p = 0.0018). Additionally, the change in ALSFRS-R between pre- and mid-intervention significantly differed between groups (p = 0.0071).</p><p><strong>Interpretation: </strong>Tele-tDCS was feasible, safe, and well-tolerated in individuals with ALS. Preliminary efficacy results suggest that tele-tDCS may slow disease progression, underscoring the potential of tele-tDCS as a promising home-based neuromodulatory intervention in ALS management.</p><p><strong>Trial registration: </strong>Clinical trial registration: NCT04866771.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combination Therapy With Vigabatrin and Prednisolone Versus Vigabatrin Alone for Infantile Spasms.","authors":"Rachata Boonkrongsak, Kantapon Trongkamolchai, Sirorat Suwannachote, Somjit Sri-Udomkajorn, Raviwan Wittawassamrankul, Ravindra Arya, Kullasate Sakpichaisakul","doi":"10.1002/acn3.70034","DOIUrl":"https://doi.org/10.1002/acn3.70034","url":null,"abstract":"<p><strong>Objective: </strong>The study evaluated the effectiveness of combination therapy with vigabatrin and prednisolone versus vigabatrin alone for treating infantile epileptic spasms syndrome (IESS).</p><p><strong>Methods: </strong>This single-center, single-blind, randomized trial enrolled infants aged 2-14 months with new-onset IESS, randomly assigned them (1:1) to receive either combination therapy with vigabatrin (100-150 mg/kg/day) and prednisolone (40-60 mg/day) or vigabatrin alone. The primary outcome was sustained spasm remission between days 14 and 42. The trial (ClinicalTrials.gov identifier) was terminated early due to an interim analysis revealing a significant difference between treatment groups.</p><p><strong>Results: </strong>In all, 17 infants were assigned to combination therapy and 24 to vigabatrin alone. The median lead time to treatment for combination therapy was 30 days, compared to 60 days for the vigabatrin group (p = 0.442). Sustained spasm remission between days 14 and 42 occurred in 13 (77%) of 17 infants on combination therapy and in 8 (33%) of 24 infants on vigabatrin alone (OR 6.5, 95% CI 1.7, 29.6, p = 0.009). Combination therapy was more effective in achieving an electroclinical response by day 14 (OR 9.3, 95% CI 2.0, 54.3, p = 0.006) but not by day 42 (OR 1.9, 95% CI 0.5, 7.1, p = 0.351). Hospitalization occurred in six (35%) infants in the combination therapy group and two (8%) in the vigabatrin alone group (p = 0.05). One death was reported in the vigabatrin group.</p><p><strong>Interpretation: </strong>Despite early termination, this study showed that combination therapy is significantly more effective in achieving clinical remission of spasms and an electroclinical response by day 14.</p><p><strong>Trial registration: </strong>NCT04302116.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Universal Proteomic Signature After Exercise-Induced Muscle Injury in Muscular Dystrophies.","authors":"Mads G Stemmerik, Benjamin Barthel, Nanna R Andersen, Sofie V Skriver, Alan J Russell, John Vissing","doi":"10.1002/acn3.70035","DOIUrl":"https://doi.org/10.1002/acn3.70035","url":null,"abstract":"<p><strong>Objective: </strong>Several neuromuscular disorders (NMDs) are characterized by progressive muscle damage and are marked by the elevation of circulating muscle proteins from activity-related injury. Despite a diverse array of genetic drivers, many NMDs share similar patterns of exercise intolerance and higher concentrations of muscle injury proteins relative to unaffected individuals. While the interplay between the nature of the muscle injury and the specific genetic driver is poorly understood, the similarities exhibited by various NMDs suggest that a common proteomic signature of muscle injury may exist.</p><p><strong>Methods: </strong>We used an established exercise challenge and the SOMAscan proteomics platform to study the baseline and post-exercise proteomic profiles in a cross-sectional study of three different muscular dystrophies: Becker muscular dystrophy (BMD) and limb girdle muscular dystrophy types R9 and R12.</p><p><strong>Results: </strong>Our Results Uncover a Common Signature of Circulating Proteins That Are Elevated in all Three Myopathies, Some of Which Are Further Elevated by Exercise in Becker Muscular Dystrophy and Limb Girdle Muscular Dystrophy Type R9, and Others That Are Not Responsive to Exercise.</p><p><strong>Interpretation: </strong>Interestingly, these two signatures exhibit opposing trajectories with age in a larger cross-sectional cohort of BMD individuals. This research represents a first step toward defining an annotated protein signature coupled with activity-injury, a defining pathophysiological feature of many myopathies.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}