{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T16:46:27Z","timestamp":1794329187834,"version":"4.9.0"},"reference-count":121,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T00:00:00Z","timestamp":1745193600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["neurotherapeuticsjournal.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Neurotherapeutics"],"published-print":{"date-parts":[[2025,7]]},"DOI":"10.1016\/j.neurot.2025.e00601","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T07:02:37Z","timestamp":1746774157000},"page":"e00601","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":42,"title":["Progressive multiple sclerosis: Evaluating current therapies and exploring future treatment strategies"],"prefix":"10.1016","volume":"22","author":[{"given":"Marelisa","family":"Albelo-Mart\u00ednez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed","family":"Rizvi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.neurot.2025.e00601_bib1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13317-019-0117-5","article-title":"Brain atrophy in multiple sclerosis: mechanisms, clinical relevance and treatment options","volume":"10","author":"Andravizou","year":"2019","journal-title":"Autoimmuni Highlights"},{"issue":"1","key":"10.1016\/j.neurot.2025.e00601_bib2","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.ncl.2017.08.003","article-title":"New insights into multiple sclerosis clinical course from the topographical model and functional reserve","volume":"36","author":"Krieger","year":"2018","journal-title":"Neurol Clin"},{"issue":"5","key":"10.1016\/j.neurot.2025.e00601_bib3","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1007\/s00401-012-0953-0","article-title":"Primary progressive multiple sclerosis: part of the MS disease spectrum or separate disease entity?","volume":"123","author":"Antel","year":"2012","journal-title":"Acta Neuropathol"},{"issue":"2","key":"10.1016\/j.neurot.2025.e00601_bib4","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/S1474-4422(17)30470-2","article-title":"Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria","volume":"17","author":"Thompson","year":"2018","journal-title":"Lancet Neurol"},{"issue":"4","key":"10.1016\/j.neurot.2025.e00601_bib5","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1007\/s00415-019-09489-5","article-title":"A focus on secondary progressive multiple sclerosis [SPMS]: challenges in diagnosis and definition","volume":"268","author":"Inojosa","year":"2021","journal-title":"J Neurol"},{"issue":"9","key":"10.1016\/j.neurot.2025.e00601_bib6","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1093\/brain\/aww173","article-title":"Defining secondary progressive multiple sclerosis","volume":"139","author":"Lorscheider","year":"2016","journal-title":"Brain"},{"issue":"Suppl 1","key":"10.1016\/j.neurot.2025.e00601_bib7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000367614","article-title":"New multiple sclerosis phenotypic classification","volume":"72","author":"Lublin","year":"2014","journal-title":"Eur Neurol"},{"issue":"5","key":"10.1016\/j.neurot.2025.e00601_bib8","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1093\/brain\/awp070","article-title":"The relation between inflammation and neurodegeneration in multiple sclerosis brains","volume":"132","author":"Frischer","year":"2009","journal-title":"Brain"},{"issue":"8","key":"10.1016\/j.neurot.2025.e00601_bib9","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1212\/WNL.0000000000012323","article-title":"Secondary progressive multiple sclerosis: new insights","volume":"97","author":"Cree","year":"2021","journal-title":"Neurology"},{"issue":"1","key":"10.1016\/j.neurot.2025.e00601_bib10","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/ene.15593","article-title":"Diagnosis and treatment of progressive multiple sclerosis: a position paper","volume":"30","author":"Pozzilli","year":"2023","journal-title":"Eur J Neurol"},{"issue":"3","key":"10.1016\/j.neurot.2025.e00601_bib11","first-page":"527","article-title":"Progressive multiple sclerosis: from pathogenic mechanisms to treatment","volume":"140","author":"Correale","year":"2017","journal-title":"Brain"},{"issue":"1","key":"10.1016\/j.neurot.2025.e00601_bib12","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s12974-022-02408-y","article-title":"Central nervous system macrophages in progressive multiple sclerosis: relationship to neurodegeneration and therapeutics","volume":"19","author":"Kamma","year":"2022","journal-title":"J Neuroinflammation"},{"issue":"Pt 11","key":"10.1016\/j.neurot.2025.e00601_bib13","doi-asserted-by":"crossref","first-page":"2705","DOI":"10.1093\/brain\/awh641","article-title":"Cortical demyelination and diffuse white matter injury in multiple sclerosis","volume":"128","author":"Kutzelnigg","year":"2005","journal-title":"Brain"},{"issue":"2","key":"10.1016\/j.neurot.2025.e00601_bib14","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S1474-4422(14)70256-X","article-title":"Pathological mechanisms in progressive multiple sclerosis","volume":"14","author":"Mahad","year":"2015","journal-title":"Lancet Neurol"},{"issue":"4","key":"10.1016\/j.neurot.2025.e00601_bib15","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.it.2023.02.002","article-title":"Multiple sclerosis: role of meningeal lymphoid aggregates in progression independent of relapse activity","volume":"44","author":"Ransohoff","year":"2023","journal-title":"Trends Immunol"},{"issue":"11","key":"10.1016\/j.neurot.2025.e00601_bib16","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1177\/13524585211013748","article-title":"Slowly expanding lesions are a marker of progressive MS - yes","volume":"27","author":"Absinta","year":"2021","journal-title":"Mult Scler"},{"issue":"10","key":"10.1016\/j.neurot.2025.e00601_bib17","doi-asserted-by":"crossref","DOI":"10.1212\/WNL.0000000000210004","article-title":"Associations between paramagnetic rim lesion evolution and clinical and radiologic disease progression in persons with multiple sclerosis","volume":"103","author":"Reeves","year":"2024","journal-title":"Neurology"},{"issue":"1","key":"10.1016\/j.neurot.2025.e00601_bib18","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s40893-016-0012-0","article-title":"The link of inflammation and neurodegeneration in progressive multiple sclerosis","volume":"1","author":"P\u00e9rez-Cerd\u00e1","year":"2016","journal-title":"Multip Scleros Demyelinat Disorder"},{"issue":"9","key":"10.1016\/j.neurot.2025.e00601_bib19","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1001\/jamaneurol.2020.1568","article-title":"Contribution of relapse-independent progression vs relapse-associated worsening to overall confirmed disability accumulation in typical relapsing multiple sclerosis in a pooled analysis of 2 randomized clinical trials","volume":"77","author":"Kappos","year":"2020","journal-title":"JAMA Neurol"},{"issue":"3","key":"10.1016\/j.neurot.2025.e00601_bib20","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1056\/NEJMoa1606468","article-title":"Ocrelizumab versus placebo in primary progressive multiple sclerosis","volume":"376","author":"Montalban","year":"2017","journal-title":"N Engl J Med"},{"issue":"10127","key":"10.1016\/j.neurot.2025.e00601_bib21","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/S0140-6736(18)30475-6","article-title":"Siponimod versus placebo in secondary progressive multiple sclerosis [EXPAND]: a double-blind, randomised, phase 3 study","volume":"391","author":"Kappos","year":"2018","journal-title":"Lancet"},{"key":"10.1016\/j.neurot.2025.e00601_bib22","article-title":"Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis","volume":"376","author":"Hauser","year":"2016","journal-title":"N Engl J Med"},{"issue":"9","key":"10.1016\/j.neurot.2025.e00601_bib23","doi-asserted-by":"crossref","first-page":"3147","DOI":"10.1093\/brain\/awac016","article-title":"How patients with multiple sclerosis acquire disability","volume":"145","author":"Lublin","year":"2022","journal-title":"Brain"},{"issue":"1","key":"10.1016\/j.neurot.2025.e00601_bib24","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s40120-021-00239-2","article-title":"Comprehensive approach to management of multiple sclerosis: addressing invisible symptoms\u2014a narrative review","volume":"10","author":"Lakin","year":"2021","journal-title":"Neurol Ther"},{"issue":"1","key":"10.1016\/j.neurot.2025.e00601_bib25","first-page":"Cd012732","article-title":"Rehabilitation for people with multiple sclerosis: an overview of Cochrane Reviews","volume":"1","author":"Amatya","year":"2019","journal-title":"Cochrane Database Syst Rev"},{"issue":"12","key":"10.1016\/j.neurot.2025.e00601_bib26","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1177\/1352458520915629","article-title":"Exercise and lifestyle physical activity recommendations for people with multiple sclerosis throughout the disease course","volume":"26","author":"Kalb","year":"2020","journal-title":"Mult Scler"},{"key":"10.1016\/j.neurot.2025.e00601_bib27","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.msard.2019.06.019","article-title":"The effect of cycling using active-passive trainers on spasticity, cardiovascular fitness, function and quality of life in people with moderate to severe Multiple Sclerosis [MS]; a feasibility study","volume":"34","author":"Barclay","year":"2019","journal-title":"Mult Scler Relat Disord"},{"issue":"4","key":"10.1016\/j.neurot.2025.e00601_bib28","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1177\/1352458509360040","article-title":"Fatigue, mood and quality of life improve in MS patients after progressive resistance training","volume":"16","author":"Dalgas","year":"2010","journal-title":"Mult Scler"},{"issue":"1","key":"10.1016\/j.neurot.2025.e00601_bib29","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s40120-017-0086-4","article-title":"Vitamin D and multiple sclerosis: a comprehensive review","volume":"7","author":"Sintzel","year":"2018","journal-title":"Neurol Ther"},{"key":"10.1016\/j.neurot.2025.e00601_bib30","series-title":"High-dose cholecalciferol reduces multiple sclerosis disease activity after a clinically isolated syndrome: results of a 24-month placebo-controlled randomized trial [D-lay MS]","author":"Thouvenot","year":"2024"},{"issue":"2","key":"10.1016\/j.neurot.2025.e00601_bib31","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1177\/1545968308320641","article-title":"Effect of exercise training on walking mobility in multiple sclerosis: a meta-analysis","volume":"23","author":"Snook","year":"2009","journal-title":"Neurorehabilitation Neural Repair"},{"key":"10.1016\/j.neurot.2025.e00601_bib32","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/1471-2377-14-15","article-title":"Mindfulness based interventions in multiple sclerosis--a systematic review","volume":"14","author":"Simpson","year":"2014","journal-title":"BMC Neurol"},{"issue":"8","key":"10.1016\/j.neurot.2025.e00601_bib33","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1177\/1352458515609794","article-title":"Smoking is a major preventable risk factor for multiple sclerosis","volume":"22","author":"Hedstr\u00f6m","year":"2016","journal-title":"Mult Scler"},{"issue":"1","key":"10.1016\/j.neurot.2025.e00601_bib34","doi-asserted-by":"crossref","first-page":"27","DOI":"10.5014\/ajot.2014.008672","article-title":"Systematic review of occupational therapy\u2013related interventions for people with multiple sclerosis: Part 1. Activity and participation","volume":"68","author":"Yu","year":"2014","journal-title":"Am J Occup Ther"},{"key":"10.1016\/j.neurot.2025.e00601_bib35","doi-asserted-by":"crossref","DOI":"10.3389\/fneur.2018.00149","article-title":"The efficacy of psychological interventions for managing fatigue in people with multiple sclerosis: a systematic review and meta-analysis","volume":"9","author":"Phyo","year":"2018","journal-title":"Front Neurol"},{"key":"10.1016\/j.neurot.2025.e00601_bib36","doi-asserted-by":"crossref","DOI":"10.1016\/j.msard.2022.104460","article-title":"A review of current rehabilitation practices and their benefits in patients with multiple sclerosis","volume":"69","author":"Iodice","year":"2023","journal-title":"Mult Scler Relat Disord"},{"issue":"6","key":"10.1016\/j.neurot.2025.e00601_bib37","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.brat.2012.03.001","article-title":"A pilot randomised controlled trial of an Internet-based cognitive behavioural therapy self-management programme [MS Invigor8] for multiple sclerosis fatigue","volume":"50","author":"Moss-Morris","year":"2012","journal-title":"Behav Res Ther"},{"issue":"3","key":"10.1016\/j.neurot.2025.e00601_bib38","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/S1474-4422(24)00027-9","article-title":"Clinical trials for progressive multiple sclerosis: progress, new lessons learned, and remaining challenges","volume":"23","author":"Chataway","year":"2024","journal-title":"Lancet Neurol"},{"issue":"4","key":"10.1016\/j.neurot.2025.e00601_bib39","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1002\/ana.21867","article-title":"Rituximab in patients with primary progressive multiple sclerosis: results of a randomized double-blind placebo-controlled multicenter trial","volume":"66","author":"Hawker","year":"2009","journal-title":"Ann Neurol"},{"issue":"6","key":"10.1016\/j.neurot.2025.e00601_bib40","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1007\/s13311-023-01415-y","article-title":"Effectiveness of ocrelizumab in primary progressive multiple sclerosis: a multicenter, retrospective, real-world study [OPPORTUNITY]","volume":"20","author":"Chisari","year":"2023","journal-title":"Neurotherapeutics"},{"key":"10.1016\/j.neurot.2025.e00601_bib41","doi-asserted-by":"crossref","DOI":"10.1177\/1756286421990500","article-title":"Should ocrelizumab be used in non-active primary progressive multiple sclerosis? Time for a re-assessment","volume":"14","author":"Manouchehri","year":"2021","journal-title":"Therapeut Adv Neurolog Disord"},{"issue":"11","key":"10.1016\/j.neurot.2025.e00601_bib42","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1212\/WNL.56.11.1505","article-title":"Group\u2217 tSS. Randomized controlled trial of interferon-beta-1a in secondary progressive MS","volume":"56","author":"Li","year":"2001","journal-title":"Neurology"},{"issue":"4","key":"10.1016\/j.neurot.2025.e00601_bib43","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.4049\/jimmunol.1090138","article-title":"Glatiramer acetate treatment of multiple sclerosis: an immunological perspective","volume":"186","author":"Racke","year":"2011","journal-title":"J Immunol"},{"issue":"1","key":"10.1016\/j.neurot.2025.e00601_bib44","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1002\/ana.21079","article-title":"Glatiramer acetate in primary progressive multiple sclerosis: results of a multinational, multicenter, double-blind, placebo-controlled trial","volume":"61","author":"Wolinsky","year":"2007","journal-title":"Ann Neurol"},{"issue":"10023","key":"10.1016\/j.neurot.2025.e00601_bib45","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1016\/S0140-6736(15)01314-8","article-title":"Oral fingolimod in primary progressive multiple sclerosis [INFORMS]: a phase 3, randomised, double-blind, placebo-controlled trial","volume":"387","author":"Lublin","year":"2016","journal-title":"Lancet"},{"issue":"5","key":"10.1016\/j.neurot.2025.e00601_bib46","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/S1474-4422(18)30069-3","article-title":"Effect of natalizumab on disease progression in secondary progressive multiple sclerosis [ASCEND]: a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension","volume":"17","author":"Kapoor","year":"2018","journal-title":"Lancet Neurol"},{"issue":"3","key":"10.1016\/j.neurot.2025.e00601_bib47","doi-asserted-by":"crossref","DOI":"10.1212\/NXI.0000000000001148","article-title":"Efficacy and safety of masitinib in progressive forms of multiple sclerosis: a randomized, phase 3, clinical trial","volume":"9","author":"Vermersch","year":"2022","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"issue":"9","key":"10.1016\/j.neurot.2025.e00601_bib48","doi-asserted-by":"crossref","first-page":"5093","DOI":"10.1007\/s00415-022-11166-z","article-title":"Siponimod vs placebo in active secondary progressive multiple sclerosis: a post hoc analysis from the phase 3 EXPAND study","volume":"269","author":"Gold","year":"2022","journal-title":"J Neurol"},{"issue":"7","key":"10.1016\/j.neurot.2025.e00601_bib49","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1007\/s40263-021-00805-0","article-title":"Comparative efficacy and safety of ozanimod and dimethyl fumarate for relapsing-remitting multiple sclerosis using matching-adjusted indirect comparison","volume":"35","author":"Cohan","year":"2021","journal-title":"CNS Drugs"},{"issue":"9139","key":"10.1016\/j.neurot.2025.e00601_bib50","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1016\/S0140-6736(98)10039-9","article-title":"Placebo-controlled multicentre randomised trial of interferon beta-1b in treatment of secondary progressive multiple sclerosis. European Study Group on interferon beta-1b in secondary progressive MS","volume":"352","author":"Kappos","year":"1998","journal-title":"Lancet"},{"issue":"5","key":"10.1016\/j.neurot.2025.e00601_bib51","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1212\/WNL.59.5.679","article-title":"Benefit of interferon beta-1a on MSFC progression in secondary progressive MS","volume":"59","author":"Cohen","year":"2002","journal-title":"Neurology"},{"issue":"9350","key":"10.1016\/j.neurot.2025.e00601_bib52","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1016\/S0140-6736(02)12023-X","article-title":"Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial","volume":"360","author":"Hartung","year":"2002","journal-title":"Lancet"},{"issue":"12","key":"10.1016\/j.neurot.2025.e00601_bib53","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1056\/NEJMoa1206328","article-title":"Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis","volume":"367","author":"Fox","year":"2012","journal-title":"N Engl J Med"},{"issue":"14","key":"10.1016\/j.neurot.2025.e00601_bib54","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1056\/NEJMoa1014656","article-title":"Randomized trial of oral teriflunomide for relapsing multiple sclerosis","volume":"365","author":"O\u2019Connor","year":"2011","journal-title":"N Engl J Med"},{"issue":"5","key":"10.1016\/j.neurot.2025.e00601_bib55","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1056\/NEJMoa0902533","article-title":"A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis","volume":"362","author":"Giovannoni","year":"2010","journal-title":"N Engl J Med"},{"key":"10.1016\/j.neurot.2025.e00601_bib56","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.jns.2019.10.1444","article-title":"Reduction of risk of secondary progressive multiple sclerosis within two years of treatment with cladribine tablets: an analysis of the clarity study","volume":"405","author":"Vermersch","year":"2019","journal-title":"J Neurol Sci"},{"issue":"9","key":"10.1016\/j.neurot.2025.e00601_bib57","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1056\/NEJMoa044397","article-title":"A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis","volume":"354","author":"Polman","year":"2006","journal-title":"N Engl J Med"},{"issue":"6","key":"10.1016\/j.neurot.2025.e00601_bib58","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1056\/NEJMoa1917246","article-title":"Ofatumumab versus teriflunomide in multiple sclerosis","volume":"383","author":"Hauser","year":"2020","journal-title":"N Engl J Med"},{"issue":"9936","key":"10.1016\/j.neurot.2025.e00601_bib59","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.1016\/S0140-6736(13)62242-4","article-title":"Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis [MS-STAT]: a randomised, placebo-controlled, phase 2 trial","volume":"383","author":"Chataway","year":"2014","journal-title":"Lancet"},{"key":"10.1016\/j.neurot.2025.e00601_bib60","series-title":"European committee for treatment and research in multiple sclerosis [ECTRIMS]","article-title":"Evaluating the effectiveness of simvastatin in slowing the progression of disability in secondary progressive multiple sclerosis MS-STAT2 trial]: a multicentre, randomised, placebo-controlled, double-blind phase 3 clinical trial","author":"Chataway","year":"2024"},{"issue":"7","key":"10.1016\/j.neurot.2025.e00601_bib61","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s11940-021-00677-1","article-title":"Early aggressive treatment approaches for multiple sclerosis","volume":"23","author":"Simpson","year":"2021","journal-title":"Curr Treat Options Neurol"},{"issue":"5","key":"10.1016\/j.neurot.2025.e00601_bib62","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1001\/jamaneurol.2018.4905","article-title":"Clinical outcomes of escalation vs early intensive disease-modifying therapy in patients with multiple sclerosis","volume":"76","author":"Harding","year":"2019","journal-title":"JAMA Neurol"},{"issue":"10","key":"10.1016\/j.neurot.2025.e00601_bib63","doi-asserted-by":"crossref","first-page":"5382","DOI":"10.1007\/s00415-022-11193-w","article-title":"Early use of high-efficacy disease-modifying therapies makes the difference in people with multiple sclerosis: an expert opinion","volume":"269","author":"Filippi","year":"2022","journal-title":"J Neurol"},{"issue":"4","key":"10.1016\/j.neurot.2025.e00601_bib64","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1007\/s00401-022-02411-w","article-title":"BTK inhibition limits B-cell-T-cell interaction through modulation of B-cell metabolism: implications for multiple sclerosis therapy","volume":"143","author":"Li","year":"2022","journal-title":"Acta Neuropathol"},{"issue":"3","key":"10.1016\/j.neurot.2025.e00601_bib65","first-page":"945","article-title":"Bruton\u2019s Tyrosine Kinase is involved in innate and adaptive immunity","volume":"20","author":"Brunner","year":"2005","journal-title":"Histol Histopathol"},{"issue":"2","key":"10.1016\/j.neurot.2025.e00601_bib66","doi-asserted-by":"crossref","first-page":"123","DOI":"10.3233\/BPL-200100","article-title":"Bruton\u2019s tyrosine kinase inhibition promotes myelin repair","volume":"5","author":"Martin","year":"2020","journal-title":"Brain Plast"},{"issue":"5","key":"10.1016\/j.neurot.2025.e00601_bib67","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/s41582-023-00800-7","article-title":"Bruton tyrosine kinase inhibitors for multiple sclerosis","volume":"19","author":"Kr\u00e4mer","year":"2023","journal-title":"Nat Rev Neurol"},{"key":"10.1016\/j.neurot.2025.e00601_bib68","series-title":"40th congress of the European committee for treatment and research in multiple sclerosis [ECTRIMS] 18-20 september 2024","article-title":"Efficacy and safety of tolebrutinib versus placebo in non-relapsing secondary progressive multiple sclerosis: results from the phase 3 HERCULES trial","author":"Fox","year":"2024"},{"key":"10.1016\/j.neurot.2025.e00601_bib69","series-title":"40th congress of the European committee for treatment and research in multiple sclerosis [ECTRIMS]; 18-20 September 2024","article-title":"Efficacy and safety of tolebrutinib versus teriflunomide in relapsing multiple sclerosis: results from the phase 3 GEMINI 1 and 2 trials","author":"Oh","year":"2024"},{"key":"10.1016\/j.neurot.2025.e00601_bib70","series-title":"A study to evaluate the efficacy and safety of fenebrutinib compared with ocrelizumab in adult participants with primary progressive multiple sclerosis [FENtrepid]","author":"Roche","year":"2024"},{"issue":"17_supplement_1","key":"10.1016\/j.neurot.2025.e00601_bib71","doi-asserted-by":"crossref","first-page":"3669","DOI":"10.1212\/WNL.0000000000205299","article-title":"Impact of fenebrutinib treatment on MRI outcomes and cerebrospinal fluid penetrance in multiple sclerosis: results from the phase II FENopta study [S31.004]","volume":"102","author":"Bar-Or","year":"2024","journal-title":"Neurology"},{"issue":"11","key":"10.1016\/j.neurot.2025.e00601_bib72","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1016\/S1474-4422(24)00328-4","article-title":"Safety and efficacy of evobrutinib in relapsing multiple sclerosis [evolutionRMS1 and evolutionRMS2]: two multicentre, randomised, double-blind, active-controlled, phase 3 trials","volume":"23","author":"Montalban","year":"2024","journal-title":"Lancet Neurol"},{"key":"10.1016\/j.neurot.2025.e00601_bib73","series-title":"Efficacy and safety of remibrutinib compared to teriflunomide in participants with relapsing multiple sclerosis [RMS] [REMODEL-2]","year":"2024"},{"key":"10.1016\/j.neurot.2025.e00601_bib74","series-title":"A phase 2 study of orelabrutinib in patients with relapsing-remitting multiple sclerosis","year":"2023"},{"issue":"9","key":"10.1016\/j.neurot.2025.e00601_bib75","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0007258","article-title":"Masitinib [AB1010], a potent and selective tyrosine kinase inhibitor targeting KIT","volume":"4","author":"Dubreuil","year":"2009","journal-title":"PLoS One"},{"key":"10.1016\/j.neurot.2025.e00601_bib76","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/1471-2377-12-36","article-title":"Masitinib treatment in patients with progressive multiple sclerosis: a randomized pilot study","volume":"12","author":"Vermersch","year":"2012","journal-title":"BMC Neurol"},{"key":"10.1016\/j.neurot.2025.e00601_bib77","series-title":"Masitinib in the treatment of patients with primary progressive or non-active secondary progressive multiple sclerosis [MAXIMS]","author":"Science","year":"2023"},{"issue":"9","key":"10.1016\/j.neurot.2025.e00601_bib78","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1056\/NEJMoa1803583","article-title":"Phase 2 trial of ibudilast in progressive multiple sclerosis","volume":"379","author":"Fox","year":"2018","journal-title":"N Engl J Med"},{"issue":"4","key":"10.1016\/j.neurot.2025.e00601_bib79","doi-asserted-by":"crossref","first-page":"e491","DOI":"10.1212\/WNL.0000000000011314","article-title":"Effects of ibudilast on MRI measures in the phase 2 SPRINT-MS study","volume":"96","author":"Naismith","year":"2021","journal-title":"Neurology"},{"key":"10.1016\/j.neurot.2025.e00601_bib80","series-title":"European committee for treatment and research in multiple sclerosis [ECTRIMS] annual congress; Milan, Italy","article-title":"Treatment of six non-active secondary progressive MS with nasal anti-CD3 monoclonal antibody [foralumab]: safety, biomarker, and disability outcomes","author":"Chitnis","year":"2023"},{"key":"10.1016\/j.neurot.2025.e00601_bib81","series-title":"A study of nasal foralumab in non-active secondary progressive multiple sclerosis patients","year":"2024"},{"issue":"7","key":"10.1016\/j.neurot.2025.e00601_bib82","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1056\/NEJMoa2309439","article-title":"Inhibition of CD40L with frexalimab in multiple sclerosis","volume":"390","author":"Vermersch","year":"2024","journal-title":"N Engl J Med"},{"key":"10.1016\/j.neurot.2025.e00601_bib83","series-title":"Efficacy and safety study of frexalimab [SAR441344] in adults with nonrelapsing secondary progressive multiple sclerosis [FREVIVA]","year":"2024"},{"key":"10.1016\/j.neurot.2025.e00601_bib84","article-title":"Vidofludimus calcium, a next generation DHODH inhibitor for the Treatment of relapsing-remitting multiple sclerosis","volume":"43","author":"Muehler","year":"2020","journal-title":"Multip Scleros Relat Disord"},{"issue":"2","key":"10.1016\/j.neurot.2025.e00601_bib85","doi-asserted-by":"crossref","DOI":"10.1093\/braincomms\/fcad072","article-title":"A potential protective role of the nuclear receptor-related factor 1 [Nurr1] in multiple sclerosis motor cortex: a neuropathological study","volume":"5","author":"Pansieri","year":"2023","journal-title":"Brain Commun"},{"issue":"11","key":"10.1016\/j.neurot.2025.e00601_bib86","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1038\/nrneurol.2013.209","article-title":"NURR1 in Parkinson disease--from pathogenesis to therapeutic potential","volume":"9","author":"Decressac","year":"2013","journal-title":"Nat Rev Neurol"},{"issue":"3","key":"10.1016\/j.neurot.2025.e00601_bib87","doi-asserted-by":"crossref","first-page":"705","DOI":"10.14336\/AD.2019.0718","article-title":"The critical role of Nurr1 as a mediator and therapeutic target in Alzheimer\u2019s disease-related pathogenesis","volume":"11","author":"Jeon","year":"2020","journal-title":"Aging Dis"},{"key":"10.1016\/j.neurot.2025.e00601_bib88","series-title":"Study to evaluate efficacy, Safety, and Tolerability of IMU-838 in Patients With Progressive Multiple Sclerosis [CALLIPER]","author":"Ag","year":"2024"},{"issue":"3","key":"10.1016\/j.neurot.2025.e00601_bib89","doi-asserted-by":"crossref","DOI":"10.1212\/NXI.0000000000200208","article-title":"Safety and dose-response of vidofludimus calcium in relapsing multiple sclerosis: extended results of a placebo-controlled phase 2 trial","volume":"11","author":"Fox","year":"2024","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"issue":"4","key":"10.1016\/j.neurot.2025.e00601_bib90","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/s41408-021-00459-7","article-title":"CAR-T cell therapy: current limitations and potential strategies","volume":"11","author":"Sterner","year":"2021","journal-title":"Blood Cancer J"},{"issue":"8","key":"10.1016\/j.neurot.2025.e00601_bib91","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1056\/NEJMoa2308917","article-title":"CD19 CAR T-cell therapy in autoimmune disease - a case series with follow-up","volume":"390","author":"M\u00fcller","year":"2024","journal-title":"N Engl J Med"},{"issue":"76","key":"10.1016\/j.neurot.2025.e00601_bib92","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.abo0777","article-title":"Antigen-specific depletion of CD4[+] T cells by CAR T cells reveals distinct roles of higher- and lower-affinity TCRs during autoimmunity","volume":"7","author":"Yi","year":"2022","journal-title":"Sci Immunol"},{"issue":"10","key":"10.1016\/j.neurot.2025.e00601_bib93","doi-asserted-by":"crossref","first-page":"6526","DOI":"10.1007\/s00415-024-12642-4","article-title":"Chimeric antigen receptor T-cell therapy for autoimmune diseases of the central nervous system: a systematic literature review","volume":"271","author":"Konitsioti","year":"2024","journal-title":"J Neurol"},{"key":"10.1016\/j.neurot.2025.e00601_bib94","series-title":"Participants With Treatment Refractory Progressive Multiple Sclerosis","article-title":"San Francisco. A study of KYV-101, a CD19 CAR T cell therapy","author":"Bruce","year":"2024"},{"key":"10.1016\/j.neurot.2025.e00601_bib95","article-title":"The peculiar challenge of bringing CAR-T cells into the brain: perspectives in the clinical application to the treatment of pediatric central nervous system tumors","volume":"14","author":"Del","year":"2023","journal-title":"Front Immunol"},{"issue":"3","key":"10.1016\/j.neurot.2025.e00601_bib96","doi-asserted-by":"crossref","DOI":"10.3390\/ijms23031337","article-title":"Genome editing using CRISPR-Cas9 and autoimmune diseases: a comprehensive review","volume":"23","author":"Lee","year":"2022","journal-title":"Int J Mol Sci"},{"issue":"10","key":"10.1016\/j.neurot.2025.e00601_bib97","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1038\/s41593-023-01432-2","article-title":"A genome-wide in vivo CRISPR screen identifies essential regulators of T cell migration to the CNS in a multiple sclerosis model","volume":"26","author":"Kendirli","year":"2023","journal-title":"Nat Neurosci"},{"key":"10.1016\/j.neurot.2025.e00601_bib98","first-page":"198","article-title":"The nuclear receptor Nr4a1 acts as a microglia rheostat and serves as a therapeutic target in autoimmune-driven central nervous system inflammation","author":"Rothe","year":"2017","journal-title":"J Immunol"},{"key":"10.1016\/j.neurot.2025.e00601_bib99","doi-asserted-by":"crossref","DOI":"10.1016\/j.expneurol.2019.112965","article-title":"LINGO-1 deficiency promotes nerve regeneration through reduction of cell apoptosis, inflammation, and glial scar after spinal cord injury in mice","volume":"320","author":"Huang","year":"2019","journal-title":"Exp Neurol"},{"issue":"7","key":"10.1016\/j.neurot.2025.e00601_bib100","doi-asserted-by":"crossref","DOI":"10.3390\/ijms24076373","article-title":"Mechanisms of demyelination and remyelination strategies for multiple sclerosis","volume":"24","author":"Zhao","year":"2023","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.neurot.2025.e00601_bib101","first-page":"1","article-title":"A review on stem cell therapy for multiple sclerosis: special focus on human embryonic stem cells","volume":"11","author":"Shroff","year":"2018","journal-title":"Stem Cells Clon"},{"key":"10.1016\/j.neurot.2025.e00601_bib102","first-page":"53","article-title":"Autologous hematopoietic stem cell transplantation [AHSCT]: an evolving treatment avenue in multiple sclerosis","volume":"15","author":"Mohammadi","year":"2021","journal-title":"Biologics"},{"issue":"9","key":"10.1016\/j.neurot.2025.e00601_bib103","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1212\/WNL.0000000000003660","article-title":"High-dose immunosuppressive therapy and autologous HCT for relapsing-remitting MS","volume":"88","author":"Nash","year":"2017","journal-title":"Neurology"},{"key":"10.1016\/j.neurot.2025.e00601_bib104","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.reth.2022.07.003","article-title":"Mesenchymal stem cell therapy: a review of clinical trials for multiple sclerosis","volume":"21","author":"Alanazi","year":"2022","journal-title":"Regen Ther"},{"issue":"1","key":"10.1016\/j.neurot.2025.e00601_bib105","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1186\/s13063-019-3346-z","article-title":"MEsenchymal StEm cells for Multiple Sclerosis [MESEMS]: a randomized, double blind, cross-over phase I\/II clinical trial with autologous mesenchymal stem cells for the therapy of multiple sclerosis","volume":"20","author":"Uccelli","year":"2019","journal-title":"Trials"},{"issue":"10111","key":"10.1016\/j.neurot.2025.e00601_bib106","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.1016\/S0140-6736(17)32346-2","article-title":"Clemastine fumarate as a remyelinating therapy for multiple sclerosis [ReBUILD]: a randomised, controlled, double-blind, crossover trial","volume":"390","author":"Green","year":"2017","journal-title":"Lancet"},{"issue":"12","key":"10.1016\/j.neurot.2025.e00601_bib107","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1016\/S1474-4422(20)30347-1","article-title":"Safety and efficacy of MD1003 [high-dose biotin] in patients with progressive multiple sclerosis [SPI2]: a randomised, double-blind, placebo-controlled, phase 3 trial","volume":"19","author":"Cree","year":"2020","journal-title":"Lancet Neurol"},{"issue":"3","key":"10.1016\/j.neurot.2025.e00601_bib108","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S1474-4422(16)30377-5","article-title":"Safety and efficacy of opicinumab in acute optic neuritis [RENEW]: a randomised, placebo-controlled, phase 2 trial","volume":"16","author":"Cadavid","year":"2017","journal-title":"Lancet Neurol"},{"issue":"18","key":"10.1016\/j.neurot.2025.e00601_bib109","doi-asserted-by":"crossref","first-page":"e2313","DOI":"10.1212\/WNL.0000000000011863","article-title":"Repurposing domperidone in secondary progressive multiple sclerosis","volume":"96","author":"Koch","year":"2021","journal-title":"Neurology"},{"issue":"7471","key":"10.1016\/j.neurot.2025.e00601_bib110","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/nature12647","article-title":"A regenerative approach to the treatment of multiple sclerosis","volume":"502","author":"Deshmukh","year":"2013","journal-title":"Nature"},{"issue":"1","key":"10.1016\/j.neurot.2025.e00601_bib111","doi-asserted-by":"crossref","first-page":"3420","DOI":"10.1038\/s41467-020-17243-z","article-title":"EEF1A1 deacetylation enables transcriptional activation of remyelination","volume":"11","author":"Duman","year":"2020","journal-title":"Nat Commun"},{"issue":"7555","key":"10.1016\/j.neurot.2025.e00601_bib112","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/nature14335","article-title":"Drug-based modulation of endogenous stem cells promotes functional remyelination in vivo","volume":"522","author":"Najm","year":"2015","journal-title":"Nature"},{"issue":"15_supplement","key":"10.1016\/j.neurot.2025.e00601_bib113","doi-asserted-by":"crossref","first-page":"P3.2","DOI":"10.1212\/WNL.92.15_supplement.P3.2-072","article-title":"Phase 2 AFFINITY trial evaluates opicinumab in a targeted population of patients with relapsing multiple sclerosis: rationale, design and baseline characteristics [P3.2-072]","volume":"92","author":"Zhu","year":"2019","journal-title":"Neurology"},{"issue":"2","key":"10.1016\/j.neurot.2025.e00601_bib114","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1007\/s00415-016-8341-7","article-title":"Lesion remyelinating activity of GSK239512 versus placebo in patients with relapsing-remitting multiple sclerosis: a randomised, single-blind, phase II study","volume":"264","author":"Schwartzbach","year":"2017","journal-title":"J Neurol"},{"issue":"11","key":"10.1016\/j.neurot.2025.e00601_bib115","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/S1474-4422(21)00301-X","article-title":"Safety, tolerability, and activity of mesenchymal stem cells versus placebo in multiple sclerosis [MESEMS]: a phase 2, randomised, double-blind crossover trial","volume":"20","author":"Uccelli","year":"2021","journal-title":"Lancet Neurol"},{"issue":"8","key":"10.1016\/j.neurot.2025.e00601_bib116","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s11910-024-01354-x","article-title":"Artificial intelligence and multiple sclerosis","volume":"24","author":"Amin","year":"2024","journal-title":"Curr Neurol Neurosci Rep"},{"issue":"5","key":"10.1016\/j.neurot.2025.e00601_bib117","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1007\/s00415-019-09518-3","article-title":"Artificial intelligence as an emerging technology in the current care of neurological disorders","volume":"268","author":"Patel","year":"2021","journal-title":"J Neurol"},{"key":"10.1016\/j.neurot.2025.e00601_bib118","doi-asserted-by":"crossref","DOI":"10.3389\/fneur.2020.546744","article-title":"LesionQuant for assessment of MRI in multiple sclerosis-A promising supplement to the visual scan inspection","volume":"11","author":"Brune","year":"2020","journal-title":"Front Neurol"},{"key":"10.1016\/j.neurot.2025.e00601_bib119","series-title":"Famciclovir in multiple sclerosis","year":"2022"},{"key":"10.1016\/j.neurot.2025.e00601_bib120","series-title":"Effects of antiviral therapies on epstein-barr virus replication ClinicalTrials.gov ID NCT05957913","year":"2024"},{"key":"10.1016\/j.neurot.2025.e00601_bib121","series-title":"Phase 1\/2 study to evaluate the safety and efficacy of ATA188 in subjects with progressive multiple sclerosis [EMBOLD]","year":"2024"}],"container-title":["Neurotherapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1878747925000790?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1878747925000790?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T13:00:15Z","timestamp":1755090015000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1878747925000790"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":121,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["S1878747925000790"],"URL":"https:\/\/doi.org\/10.1016\/j.neurot.2025.e00601","relation":{},"ISSN":["1878-7479"],"issn-type":[{"value":"1878-7479","type":"print"}],"subject":[],"published":{"date-parts":[[2025,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Progressive multiple sclerosis: Evaluating current therapies and exploring future treatment strategies","name":"articletitle","label":"Article Title"},{"value":"Neurotherapeutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.neurot.2025.e00601","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Author(s). Published by Elsevier Inc. on behalf of American Society for Experimental NeuroTherapeutics.","name":"copyright","label":"Copyright"}],"article-number":"e00601"}}