{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:13:08Z","timestamp":1791216788752,"version":"4.1.0"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T00:00:00Z","timestamp":1730332800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Eledon Pharmaceuticals"}],"content-domain":{"domain":["www.plosmedicine.org"],"crossmark-restriction":false},"short-container-title":["PLoS Med"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>The interaction of CD40L and its receptor CD40 on activated T cells and B cells respectively control pro-inflammatory activation in the pathophysiology of autoimmunity and transplant rejection. Previous studies have implicated signaling pathways involving CD40L (interchangeably referred to as CD154), as well as adaptive and innate immune cell activation, in the induction of neuroinflammation in neurodegenerative diseases. This study aimed to assess the safety, tolerability, and impact on pro-inflammatory biomarker profiles of an anti CD40L antibody, tegoprubart, in individuals with amyotrophic lateral sclerosis (ALS).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods and findings<\/jats:title>\n<jats:p>In this multicenter dose-escalating open-label Phase 2A study, 54 participants with a diagnosis of ALS received 6 infusions of tegoprubart administered intravenously every 2 weeks. The study was comprised of 4 dose cohorts: 1 mg\/kg, 2 mg\/kg, 4 mg\/kg, and 8 mg\/kg. The primary endpoint of the study was safety and tolerability. Exploratory endpoints assessed the pharmacokinetics of tegoprubart as well as anti-drug antibody (ADA) responses, changes in disease progression utilizing the Revised ALS Functional Rating Scale (ALSFRS-R), CD154 target engagement, changes in pro-inflammatory biomarkers, and neurofilament light chain (NFL).<\/jats:p>\n<jats:p>Seventy subjects were screened, and 54 subjects were enrolled in the study. Forty-nine of 54 subjects completed the study (90.7%) receiving all 6 infusions of tegoprubart and completing their final follow-up visit. The most common treatment emergent adverse events (TEAEs) overall (&gt;10%) were fatigue (25.9%), falls (22.2%), headaches (20.4%), and muscle spasms (11.1%). Mean tegoprubart plasma concentrations increased proportionally with increasing dose with a half-life of approximately 24 days. ADA titers were low and circulating levels of tegoprubart were as predicted for all cohorts. Tegoprubart demonstrated dose dependent target engagement associated and a reduction in 18 pro-inflammatory biomarkers in circulation.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Tegoprubart appeared to be safe and well tolerated in adults with ALS demonstrating dose-dependent reduction in pro-inflammatory chemokines and cytokines associated with ALS. These results warrant further clinical studies with sufficient power and duration to assess clinical outcomes as a potential treatment for adults with ALS.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Trial registration<\/jats:title>\n<jats:p>Clintrials.gov ID:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04322149\" xlink:type=\"simple\">NCT04322149<\/jats:ext-link>.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pmed.1004469","type":"journal-article","created":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T17:23:05Z","timestamp":1730395385000},"page":"e1004469","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Safety and tolerability of tegoprubart in patients with amyotrophic lateral sclerosis: A Phase 2A clinical trial"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9863-4948","authenticated-orcid":true,"given":"Steven","family":"Perrin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shafeeq","family":"Ladha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Maragakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6135-035X","authenticated-orcid":true,"given":"Michael H.","family":"Rivner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Katz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Genge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Olney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale","family":"Lange","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daragh","family":"Heitzman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Bodkin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Jawdat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1713-545X","authenticated-orcid":true,"given":"Namita A.","family":"Goyal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7745-5722","authenticated-orcid":true,"given":"Jeffrey D.","family":"Bornstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Mak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley H.","family":"Appel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0505-1168","authenticated-orcid":true,"given":"Sabrina","family":"Paganoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,10,31]]},"reference":[{"issue":"923","key":"pmed.1004469.ref001","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1136\/pmj.78.923.513","article-title":"Motor neurone disease.","volume":"78","author":"K. Talbot","year":"2002","journal-title":"Postgrad Med J.Sep"},{"issue":"5\u20136","key":"pmed.1004469.ref002","doi-asserted-by":"crossref","first-page":"310","DOI":"10.3109\/17482960802566824","article-title":"Prognostic factors in ALS: A critical review.","volume":"10","author":"A Chi\u00f2","year":"2009","journal-title":"Amyotroph Lateral Scler"},{"issue":"5","key":"pmed.1004469.ref003","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/S1474-4422(18)30089-9","article-title":"Prognosis for patients with amyotrophic lateral sclerosis: development and validation of a personalised prediction model.","volume":"17","author":"HJ Westeneng","year":"2018","journal-title":"Lancet Neurol"},{"issue":"9","key":"pmed.1004469.ref004","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1056\/NEJM199403033300901","article-title":"A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS\/Riluzole Study Group","volume":"330","author":"G Bensimon","year":"1994","journal-title":"N Engl J Med"},{"issue":"9013","key":"pmed.1004469.ref005","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1016\/S0140-6736(96)91680-3","article-title":"Dose-ranging study of riluzole in amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis\/Riluzole Study Group II","volume":"347","author":"L Lacomblez","year":"1996","journal-title":"Lancet"},{"issue":"Suppl 2","key":"pmed.1004469.ref006","doi-asserted-by":"crossref","first-page":"S22","DOI":"10.1007\/BF03160577","article-title":"The Riluzole Early Access Programme: descriptive analysis of 844 patients in France. ALS\/Riluzole Study Group III","volume":"244","author":"V Meininger","year":"1997","journal-title":"J Neurol"},{"issue":"sup1","key":"pmed.1004469.ref007","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1080\/21678421.2017.1361443","article-title":"Post-hoc analysis of randomised, placebo-controlled, double-blind study (MCI186-19) of edaravone (MCI-186) in amyotrophic lateral sclerosis.","volume":"18","author":"K Takei","year":"2017","journal-title":"Amyotroph Lateral Scler Frontotemporal Degener"},{"issue":"7\u20138","key":"pmed.1004469.ref008","doi-asserted-by":"crossref","first-page":"610","DOI":"10.3109\/21678421.2014.959024","article-title":"Confirmatory double-blind, parallel-group, placebo-controlled study of efficacy and safety of edaravone (MCI-186) in amyotrophic lateral sclerosis patients.","volume":"15","author":"K Abe","year":"2014","journal-title":"Amyotroph Lateral Scler Frontotemporal Degener"},{"key":"pmed.1004469.ref009","first-page":"405","article-title":"Autoimmunity and ALS: a comparison of animal models of immune-mediated motor neuron destruction and human ALS","volume":"56","author":"SH Appel","year":"1991","journal-title":"Adv Neurol"},{"issue":"11","key":"pmed.1004469.ref010","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1001\/archneur.1990.00530110068019","article-title":"IgG reactivity in the spinal cord and motor cortex in amyotrophic lateral sclerosis","volume":"47","author":"JI Engelhardt","year":"1990","journal-title":"Arch Neurol"},{"issue":"1","key":"pmed.1004469.ref011","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/0165-5728(84)90042-0","article-title":"Deposits of IgG and C3 in the spinal cord and motor cortex of ALS patients","volume":"6","author":"H Donnenfeld","year":"1984","journal-title":"J Neuroimmunol"},{"issue":"3","key":"pmed.1004469.ref012","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1002\/ana.410280311","article-title":"Major histocompatibility complex antigen expression in the affected tissues in amyotrophic lateral sclerosis","volume":"28","author":"LA Lampson","year":"1990","journal-title":"Ann Neurol"},{"key":"pmed.1004469.ref013","first-page":"691","article-title":"Immunologic reactions in amyotrophic lateral sclerosis brain and spinal cord tissue","volume":"140","author":"T Kawamata","year":"1992","journal-title":"Am J Pathol"},{"key":"pmed.1004469.ref014","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1001\/archneur.1993.00540010026013","article-title":"Lymphocytic infiltrates in the spinal cord in amyotrophic lateral sclerosis","volume":"50","author":"JI Engelhardt","year":"1993","journal-title":"Arch Neurol"},{"key":"pmed.1004469.ref015","first-page":"289","article-title":"Lymphocytic infiltration in the spinal cord of patients with amyotrophic lateral sclerosis","volume":"8","author":"D Troost","year":"1989","journal-title":"Clin Neuropathol"},{"issue":"2","key":"pmed.1004469.ref016","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1002\/ana.10805","article-title":"Presence of dendritic cells, MCP-1, and activated microglia\/macrophages in amyotrophic lateral sclerosis spinal cord tissue","volume":"55","author":"JS Henkel","year":"2004","journal-title":"Ann Neurol"},{"issue":"3","key":"pmed.1004469.ref017","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.mcn.2005.10.016","article-title":"The chemokine MCP-1 and the dendritic and myeloid cells it attracts are increased in the mSOD1 mouse model of ALS","volume":"31","author":"JS Henkel","year":"2006","journal-title":"Mol Cell Neurosci"},{"key":"pmed.1004469.ref018","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1111\/j.1365-2990.1990.tb01276.x","article-title":"Immunohistochemical characterization of the inflammatory infiltrate in amyotrophic lateral sclerosis.","volume":"16","author":"D Troost","year":"1990","journal-title":"Neuropathol Appl Neurobiol"},{"issue":"4","key":"pmed.1004469.ref019","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1080\/14660820410020286","article-title":"Inflammation in amyotrophic lateral sclerosis spinal cord and brain is mediated by activated macrophages, mast cells and T cells.","volume":"5","author":"MC Graves","year":"2004","journal-title":"Amyotroph Lateral Scler Other Motor Neuron Disord."},{"issue":"49","key":"pmed.1004469.ref020","doi-asserted-by":"crossref","first-page":"20960","DOI":"10.1073\/pnas.0911405106","article-title":"Activation of innate and humoral immunity in the peripheral nervous system of ALS transgenic mice","volume":"106","author":"IM Chiu","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"pmed.1004469.ref021","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/ng.557","article-title":"From transcriptome analysis to therapeutic anti-CD40L treatment in the SOD1 model of amyotrophic lateral sclerosis","volume":"42","author":"JM Lincecum","year":"2010","journal-title":"Nat Genet"},{"issue":"14","key":"pmed.1004469.ref022","doi-asserted-by":"crossref","first-page":"6550","DOI":"10.1073\/pnas.89.14.6550","article-title":"A 39-kDa Protein on Activated Helper T Cells Binds CD40 and Transduces the Signal for Cognate Activation of B Cells","volume":"89","author":"RJ Noelle","year":"1992","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6667","key":"pmed.1004469.ref023","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1038\/35393","article-title":"CD40 Ligand on Activated Platelets Triggers an Inflammatory Reaction of Endothelial Cells","volume":"391","author":"V Henn","year":"1998","journal-title":"Nature"},{"issue":"5","key":"pmed.1004469.ref024","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1073\/pnas.94.5.1931","article-title":"Functional CD40 Ligand Is Expressed on Human Vascular Endothelial Cells, Smooth Muscle Cells, and Macrophages: Implications for CD40-CD40 Ligand Signaling in Atherosclerosis","volume":"94","author":"F Mach","year":"1997","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"pmed.1004469.ref025","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1046\/j.1365-2249.1997.d01-1001.x","article-title":"Induction of Human IgE Synthesis in B Cells by a Basophilic Cell Line, KU812","volume":"108","author":"Y Yanagihara","year":"1997","journal-title":"Clin Exp Immunol"},{"issue":"3","key":"pmed.1004469.ref026","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1002\/eji.1830250335","article-title":"CD40 Ligand Is Functionally Expressed on Human Eosinophils","volume":"25","author":"JF Gauchat","year":"1995","journal-title":"Eur J Immunol"},{"issue":"6","key":"pmed.1004469.ref027","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1093\/intimm\/5.6.657","article-title":"IL-13 Induces Proliferation and Differentiation of Human B Cells Activated by the CD40","volume":"5","author":"BG Cocks","year":"1993","journal-title":"Ligand. Int Immunol"},{"issue":"1","key":"pmed.1004469.ref028","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0197-4580(01)00246-9","article-title":"Identification of CD40 Ligand in Alzheimer\u2019s Disease and in Animal Models of Alzheimer\u2019s Disease and Brain Injury.","volume":"23","author":"NY Calingasan","year":"2002","journal-title":"Neurobiol Aging"},{"issue":"8","key":"pmed.1004469.ref029","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1002\/eji.1830190818","article-title":"Activation of Human B Lymphocytes Through CD40 and Interleukin 4","volume":"19","author":"A Vall\u00e9","year":"1989","journal-title":"Eur J Immunol"},{"issue":"2","key":"pmed.1004469.ref030","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1084\/jem.178.2.669","article-title":"CD40 Expression by Human Monocytes: Regulation by Cytokines and Activation of Monocytes by the Ligand for CD40","volume":"178","author":"MR Alderson","year":"1993","journal-title":"J Exp Med"},{"issue":"4","key":"pmed.1004469.ref031","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1084\/jem.180.4.1263","article-title":"Activation of Human Dendritic Cells Through CD40 Cross-Linking","volume":"180","author":"C Caux","year":"1994","journal-title":"J Exp Med"},{"issue":"2","key":"pmed.1004469.ref032","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1006\/cimm.1999.1583","article-title":"D154 (CD40L) Induces Human Endothelial Cell Chemokine Production and Migration of Leukocyte Subsets.","volume":"198","author":"U Thienel","year":"1999","journal-title":"Cell Immunol"},{"issue":"5","key":"pmed.1004469.ref033","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1111\/j.1523-1755.2005.00663.x","article-title":"Activation of Mesangial Cells by Platelets in Systemic Lupus Erythematosus via a CD154-Dependent Induction of CD40","volume":"68","author":"Y Delmas","year":"2005","journal-title":"Kidney Int"},{"issue":"1","key":"pmed.1004469.ref034","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1002\/art.1780400117","article-title":"Immunohistologic Analysis of Renal CD40 and CD40L Expression in Lupus Nephritis and Other Glomerulonephritides.","volume":"40","author":"MJ Yellin","year":"1997","journal-title":"Arthritis Rheumatol"},{"issue":"6","key":"pmed.1004469.ref035","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/0952-7915(93)90113-7","article-title":"Role of CD40-CD40-Ligand Interaction in Ig-Isotype Switching","volume":"5","author":"R Fuleihan","year":"1993","journal-title":"Curr Opin Immunol"},{"issue":"5","key":"pmed.1004469.ref036","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1084\/jem.178.5.1567","article-title":"In Vivo CD40-Gp39 Interactions Are Essential for Thymus-Dependent Humoral Immunity. II. Prolonged Suppression of the Humoral Immune Response by an Antibody to the Ligand for CD40, Gp39","volume":"178","author":"TM Foy","year":"1993","journal-title":"J Exp Med"},{"issue":"1","key":"pmed.1004469.ref037","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1084\/jem.180.1.157","article-title":"Gp39- CD40 Interactions Are Essential for Germinal Center Formation and the Development of B Cell Memory","volume":"180","author":"TM Foy","year":"1994","journal-title":"J Exp Med"},{"issue":"6","key":"pmed.1004469.ref038","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1073\/pnas.91.6.2110","article-title":"Organization of the Human CD40L Gene: Implications for Molecular Defects in X Chromosome-Linked Hyper-IgM Syndrome and Prenatal Diagnosis","volume":"91","author":"A Villa","year":"1994","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"pmed.1004469.ref039","first-page":"131","article-title":"Follicular Helper T Cells: New Insights Into Mechanisms of Autoimmune Diseases.","volume":"13","author":"X Zhang","year":"2013","journal-title":"Ochsner J Spring."},{"key":"pmed.1004469.ref040","doi-asserted-by":"crossref","first-page":"e19552","DOI":"10.7554\/eLife.19552","article-title":"Germinal Center B Cell Development Has Distinctly Regulated Stages Completed by Disengagement From T Cell Help.","volume":"6","author":"TT Zhang","year":"2017","journal-title":"Elife"},{"issue":"4","key":"pmed.1004469.ref041","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.4049\/jimmunol.1300267","article-title":"Inhibition of CD8+ T Cell-Derived CD40 Signals Is Necessary But Not Sufficient for Foxp3+ Induced Regulatory T Cell Generation In Vivo","volume":"191","author":"D Liu","year":"2013","journal-title":"J Immunol"},{"issue":"51","key":"pmed.1004469.ref042","doi-asserted-by":"crossref","first-page":"20701","DOI":"10.1073\/pnas.1105500108","article-title":"Antigen- Specific Induced Foxp3+ Regulatory T Cells Are Generated Following CD40\/CD154 Blockade","volume":"108","author":"IR Ferrer","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"pmed.1004469.ref043","doi-asserted-by":"crossref","first-page":"183","DOI":"10.4049\/jimmunol.164.1.183","article-title":"Suppressor Effector Function of CD4+CD25+ Immunoregulatory T Cells Is Antigen Nonspecific","volume":"164","author":"AM Thornton","year":"2000","journal-title":"J Immunol"},{"key":"pmed.1004469.ref044","doi-asserted-by":"crossref","first-page":"850998","DOI":"10.3389\/fimmu.2022.850998","article-title":"Role of the CXCL13\/CXCR5 Axis in Autoimmune Diseases.","volume":"13","author":"Z Pan","year":"2022","journal-title":"Front Immunol."},{"key":"pmed.1004469.ref045","first-page":"65","article-title":"A simple sequential rejective multiple test procedure.","volume":"6","author":"S. Holm","year":"1979","journal-title":"Scand J Stat"},{"issue":"4","key":"pmed.1004469.ref046","doi-asserted-by":"crossref","first-page":"496","DOI":"10.3390\/genes15040496","article-title":"Neurofilaments in Sporadic and Familial Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.","volume":"15","author":"P Shahim","year":"2024","journal-title":"Genes (Basel)."},{"key":"pmed.1004469.ref047","doi-asserted-by":"crossref","first-page":"16021","DOI":"10.1073\/pnas.0607423103","article-title":"Wild-type microglia extend survival in PU.1 knockout mice with familial amyotrophic lateral sclerosis","volume":"103","author":"DR Beers","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pmed.1004469.ref048","doi-asserted-by":"crossref","first-page":"15558","DOI":"10.1073\/pnas.0807419105","article-title":"CD4+ T cells support glial neuroprotection, slow disease progression, and modify glial morphology in an animal model of inherited ALS","volume":"105","author":"DR Beers","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7","key":"pmed.1004469.ref049","doi-asserted-by":"crossref","first-page":"2740","DOI":"10.1371\/journal.pone.0002740","article-title":"Adaptive immune neuroprotection in G93A-SOD1 amyotrophic lateral sclerosis mice.","volume":"3","author":"R Banerjee","year":"2008","journal-title":"PLoS ONE"},{"issue":"11","key":"pmed.1004469.ref050","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1038\/s41593-020-00718-z","article-title":"Modifying macrophages at the periphery has the capacity to change microglial reactivity and to extend ALS survival","volume":"23","author":"A Chiot","year":"2020","journal-title":"Nat Neurosci"}],"container-title":["PLOS Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.1004469","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T17:23:24Z","timestamp":1730395404000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.1004469"}},"subtitle":[],"editor":[{"given":"Joshua Z.","family":"Willey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,10,31]]},"references-count":50,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,10,31]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pmed.1004469","relation":{},"ISSN":["1549-1676"],"issn-type":[{"value":"1549-1676","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,31]]}}}