The Lancet Neurology最新文献

{"title":"Safety and efficacy of intrathecal antibodies to Nogo-A in patients with acute cervical spinal cord injury: a randomised, double-blind, multicentre, placebo-controlled, phase 2b trial","authors":"Norbert Weidner, Rainer Abel, Doris Maier, Klaus Röhl, Frank Röhrich, Michael Baumberger, Margret Hund-Georgiadis, Marion Saur, Jesús Benito, Kerstin Rehahn, Mirko Aach, Andreas Badke, Jiri Kriz, Katalin Barkovits, Tim Killeen, Lynn Farner, Maryam Seif, Michèle Hubli, Katrin Marcus, Michael A Maurer, Armin Curt","doi":"10.1016/s1474-4422(24)00447-2","DOIUrl":"https://doi.org/10.1016/s1474-4422(24)00447-2","url":null,"abstract":"<h3>Background</h3>Spinal cord injury results in permanent neurological impairment and disability due to the absence of spontaneous regeneration. NG101, a recombinant human antibody, neutralises the neurite growth-inhibiting protein Nogo-A, promoting neural repair and motor recovery in animal models of spinal cord injury. We aimed to evaluate the efficacy of intrathecal NG101 on recovery in patients with acute cervical traumatic spinal cord injury.<h3>Methods</h3>This randomised, double-blind, placebo-controlled phase 2b clinical trial was done at 13 hospitals in the Czech Republic, Germany, Spain, and Switzerland. Patients aged 18–70 years with acute, complete or incomplete cervical spinal cord injury (neurological level of injury C1–C8) within 4–28 days of injury were eligible for inclusion. Participants were initially randomly assigned 1:1 to intrathecal treatment with 45 mg NG101 or placebo (phosphate-buffered saline); 18 months into the study, the ratio was adjusted to 3:1 to achieve a final distribution of 2:1 to improve enrolment and drug exposure. Randomisation was done using a centralised, computer-based randomisation system and was stratified according to nine distinct outcome categories with a validated upper extremity motor score (UEMS) prediction model based on clinical parameters at screening. Six intrathecal injections were administered every 5 days over 4 weeks, starting within 28 days of injury. Investigators, study personnel, and study participants were masked to treatment allocation. The primary outcome was change in UEMS at 6 months, analysed alongside safety in the full analysis set. The completed trial was registered at <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, <span><span>NCT03935321</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>.<h3>Findings</h3>From May 20, 2019, to July 20, 2022, 463 patients with acute traumatic cervical spinal cord injury were screened, 334 were deemed ineligible and excluded, and 129 were randomly assigned to an intervention (80 patients in the NG101 group and 49 in the placebo group). The full analysis set comprised 78 patients from the NG101 group and 48 patients from the placebo group. 107 (85%) patients were male and 19 (15%) patients were female, with a median age of 51·5 years (IQR 30·0–60·0). Across all patients, the primary endpoint showed no significant difference between groups (with UEMS change at 6 months 1·37 [95% CI –1·44 to 4·18]; placebo group mean 19·20 [SD 11·78] at baseline and 30·91 [SD 15·49] at day 168; NG101 group mean 18·23 [SD 15·14] at baseline and 31·31 [19·54] at day 168). Treatment-related adverse events were sim","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"51 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patrikios syndrome and SOD1 ALS","authors":"Peter M Andersen, Michael Benatar","doi":"10.1016/s1474-4422(24)00491-5","DOIUrl":"https://doi.org/10.1016/s1474-4422(24)00491-5","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in neuromuscular disorders 2024","authors":"Jeffrey D Rothstein, Ahmet Hoke, Payam Mohassel","doi":"10.1016/s1474-4422(24)00489-7","DOIUrl":"https://doi.org/10.1016/s1474-4422(24)00489-7","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in sleep research in 2024","authors":"Yves Dauvilliers","doi":"10.1016/s1474-4422(24)00486-1","DOIUrl":"https://doi.org/10.1016/s1474-4422(24)00486-1","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progress and future directions in spinal cord injury trials","authors":"Karlo M Pedro, Michael G Fehlings","doi":"10.1016/s1474-4422(24)00482-4","DOIUrl":"https://doi.org/10.1016/s1474-4422(24)00482-4","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Highlights in traumatic brain injury research in 2024","authors":"Virginia Newcombe, Elisa R Zanier","doi":"10.1016/s1474-4422(24)00477-0","DOIUrl":"https://doi.org/10.1016/s1474-4422(24)00477-0","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Infectious diseases research in 2024: insights into dementia","authors":"Robyn S Klein","doi":"10.1016/s1474-4422(24)00497-6","DOIUrl":"https://doi.org/10.1016/s1474-4422(24)00497-6","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"52 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cristina Sampaio: bringing rigour to research in movement disorders","authors":"Udani Samarasekera","doi":"10.1016/s1474-4422(24)00434-4","DOIUrl":"https://doi.org/10.1016/s1474-4422(24)00434-4","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to Lancet Neurol 2024; 23: 1205–13","authors":"","doi":"10.1016/s1474-4422(24)00495-2","DOIUrl":"https://doi.org/10.1016/s1474-4422(24)00495-2","url":null,"abstract":"<em>Sheth KN, Albers GW, Saver JL, et al. Intravenous glibenclamide for cerebral oedema after large hemispheric stroke (CHARM): a phase 3, double-blind, placebo-controlled, randomised trial.</em> Lancet Neurol <em>2024; <strong>23:</strong> 1205–13</em> —In this Article, the CHARM Trial investigators and the appendix have been updated. This correction has been made as of Dec 18, 2024.","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"54 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amyotrophic lateral sclerosis caused by SOD1 variants: from genetic discovery to disease prevention","authors":"Michael Benatar, Janice Robertson, Peter Munch Andersen","doi":"10.1016/s1474-4422(24)00479-4","DOIUrl":"https://doi.org/10.1016/s1474-4422(24)00479-4","url":null,"abstract":"Pathogenic variants in the superoxide dismutase 1 (<em>SOD1</em>) gene were the first identified genetic cause of amyotrophic lateral sclerosis (ALS), in 1993. This discovery enabled the development of transgenic rodent models for studying the biology of <em>SOD1</em> ALS. The understanding that <em>SOD1</em> ALS is driven by a toxic gain-of-function mutation has led to therapeutic strategies that aim to lower concentrations of SOD1 protein, an endeavour that has been complicated by the phenotypic heterogeneity of <em>SOD1</em> ALS. The successful development of genetically targeted therapies to reduce SOD1 expression, together with a better understanding of pre-symptomatic disease and the discovery of neurofilament light protein as a susceptibility/risk biomarker that predicts phenoconversion, has ushered in a new era of trials that aim to prevent clinically manifest <em>SOD1</em> ALS. The 30-year journey from gene discovery to gene therapy has not only uncovered the pathophysiology of <em>SOD1</em> ALS, but has also facilitated the development of biomarkers that should aid therapy development for all forms of ALS.","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"260 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}