{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T09:50:15Z","timestamp":1791366615713,"version":"4.3.1"},"reference-count":26,"publisher":"Georg Thieme Verlag KG","issue":"08","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":12,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arq Neuropsiquiatr"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Despite four decades of translational research, no pharmacological agent has been approved for acute traumatic spinal cord injury (SCI) based on class-I evidence. The current narrative review critically examines the seven agents evaluated in phase-II to -III clinical trials\u2014methylprednisolone (MPSS), GM-1 monosialotetrahexosylganglioside, minocycline, riluzole, anti-Nogo-A antibody NG101, VX-210, and granulocyte colony-stimulating factor (G-CSF)\u2014with emphasis on quantitative effect estimates, confidence intervals, and mechanisms of translational failure. Polylaminin, under phase-I evaluation approved by the Brazilian Health Regulatory Agency (Ag\u00eancia Nacional de Vigil\u00e2ncia Sanit\u00e1ria, ANVISA, in Portuguese), is discussed in the context of disproportionate public communication relative to the stage of evidence; available human data are limited to a small, uncontrolled, unreviewed pilot study insufficient for efficacy inferences. High-dose MPSS conferred no motor recovery benefit in a meta-analysis of 1,863 participants and was significantly associated with gastrointestinal hemorrhage (odds ratio [OR]\u2009=\u20092.07; 95%CI: 1.02\u20134.20) and respiratory infections (OR\u2009=\u20091.73; 95%CI: 1.12\u20132.68). Furthermore, GM-1 ganglioside, G-CSF, and VX-210 failed to meet the prespecified primary endpoints. Minocycline produced inconclusive results in an underpowered phase-II study. Riluzole (Riluzole in Spinal Cord Injury Study [RISCIS]), which was prematurely terminated at 55% of enrollment due to the coronavirus disease 2019 (COVID-19) pandemic, showed a significant motor benefit in patients classified as grade C according to the American Spinal Injury Association (ASIA) Impairment Scale (AIS) (+8.0 points; 95%CI: 1.5\u201314.4; 2-tailed p\u2009=\u20090.034). The Nogo Inhibition in Spinal Cord Injury (NISCI) trial (2025), the most methodologically rigorous SCI trial to date, demonstrated no primary endpoint benefit but identified functional signals in motor-incomplete injuries. In total, six structural domains of translational failure are identified and methodological solutions proposed.<\/jats:p>","DOI":"10.1055\/s-0046-1827054","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T23:19:04Z","timestamp":1786663144000},"page":"001-009","source":"Crossref","is-referenced-by-count":1,"title":["Lost in translation: why pharmacological trials keep failing in acute spinal cord injury"],"prefix":"10.1055","volume":"84","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7694-7223","authenticated-orcid":false,"given":"Abelardo Q. C.","family":"Araujo","sequence":"additional","affiliation":[{"name":"Universidade Federal do Rio de Janeiro, Instituto de Neurologia Deolindo Couto, Rio de Janeiro RJ, Brazil."},{"name":"Universidade Federal do Rio de Janeiro, Faculdade de Medicina, Rio de Janeiro RJ, Brazil."},{"name":"Universidade Federal Fluminense, Programa de P\u00f3s-Gradua\u00e7\u00e3o em Neurologia e Neuroci\u00eancias, Rio de Janeiro RJ, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"ref1","volume-title":"International Perspectives on Spinal Cord Injury","author":"World Health Organization (WHO)","year":"2013"},{"issue":"02","key":"ref2","doi-asserted-by":"publisher","first-page":"247","DOI":"10.3171\/jns.1982.57.2.0247","article-title":"Effects of intravenous methylprednisolone on spinal cord lipid peroxidation and Na+ + K+)-ATPase activity. Dose-response analysis during 1st hour after contusion injury in the cat","volume":"57","author":"E D Hall","year":"1982","journal-title":"J Neurosurg"},{"issue":"01","key":"ref3","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1001\/jama.1984.03340250025015","article-title":"Efficacy of methylprednisolone in acute spinal cord injury","volume":"251","author":"M B Bracken","year":"1984","journal-title":"JAMA"},{"issue":"20","key":"ref4","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1056\/NEJM199005173222001","article-title":"A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study","volume":"322","author":"M B Bracken","year":"1990","journal-title":"N Engl J Med"},{"issue":"20","key":"ref5","doi-asserted-by":"publisher","first-page":"1597","DOI":"10.1001\/jama.1997.03540440031029","article-title":"Administration of methylprednisolone for 24 or 48\u2009hours in the treatment of acute spinal cord injury","volume":"277","author":"M B Bracken","year":"1997","journal-title":"JAMA"},{"issue":"09","key":"ref6","doi-asserted-by":"publisher","first-page":"e841","DOI":"10.1212\/WNL.0000000000007998","article-title":"High-dose methylprednisolone for acute traumatic spinal cord injury: A meta-analysis","volume":"93","author":"Z Y Liu","year":"2019","journal-title":"Neurology"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3171\/spi.2000.93.1.0001","article-title":"Methylprednisolone for acute spinal cord injury: an inappropriate standard of care","volume":"93","author":"R J Hurlbert","year":"2000","journal-title":"J Neurosurg"},{"issue":"26","key":"ref8","doi-asserted-by":"publisher","first-page":"1829","DOI":"10.1056\/NEJM199106273242601","article-title":"Recovery of motor function after spinal-cord injury\u2013a randomized, placebo-controlled trial with GM-1 ganglioside","volume":"324","author":"F H Geisler","year":"1991","journal-title":"N Engl J Med"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"S87","DOI":"10.1097\/00007632-200112151-00015","article-title":"The Sygen multicenter acute spinal cord injury study","volume":"26","author":"F H Geisler","year":"2001","journal-title":"Spine"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1224","DOI":"10.1093\/brain\/aws072","article-title":"Results of a phase II placebo-controlled randomized trial of minocycline in acute spinal cord injury","volume":"135","author":"S Casha","year":"2012","journal-title":"Brain"},{"issue":"06","key":"ref11","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1089\/neu.2012.2622","article-title":"Delayed post-injury administration of riluzole is neuroprotective in a preclinical rodent model of cervical spinal cord injury","volume":"30","author":"Y C Wu","year":"2013","journal-title":"J Neurotrauma"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1889","DOI":"10.1089\/neu.2022.0499","article-title":"Riluzole in Spinal Cord Injury Study (RISCIS) \u2013 Pharmacokinetic (PK) Sub-Study: An Analysis of Pharmacokinetics, Pharmacodynamics, and Impact on Axonal Degradation of Riluzole in Patients With Traumatic Cervical Spinal Cord Injury Enrolled in the RISCIS Phase III Randomized Controlled Trial","volume":"40","author":"D SL Chow","year":"2023","journal-title":"J Neurotrauma"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1878","DOI":"10.1089\/neu.2023.0163","article-title":"Safety and Efficacy of Riluzole in Acute Spinal Cord Injury Study (RISCIS): A Multi-Center, Randomized, Placebo-Controlled, Double-Blinded Trial","volume":"40","author":"M G Fehlings","year":"2023","journal-title":"J Neurotrauma"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"105863","DOI":"10.1016\/j.ebiom.2025.105863","article-title":"The sodium-glutamate antagonist riluzole improves outcome after acute spinal cord injury: results from the RISCIS randomised controlled trial analyzed using a global statistical analytic technique","volume":"118","author":"M G Fehlings","year":"2025","journal-title":"EBioMedicine"},{"issue":"01","key":"ref15","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1089\/neur.2023.0114","article-title":"Safety and efficacy of riluzole in traumatic spinal cord injury: a systematic review with meta-analyses","volume":"5","author":"L J Weisbrod","year":"2024","journal-title":"Neurotrauma Rep"},{"issue":"07","key":"ref16","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1038\/nm1436","article-title":"Nogo-A-specific antibody treatment enhances sprouting and functional recovery after cervical lesion in adult primates","volume":"12","author":"P Freund","year":"2006","journal-title":"Nat Med"},{"issue":"01","key":"ref17","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/S1474-4422(24)00447-2","article-title":"Safety and efficacy of intrathecal antibodies to Nogo-A in patients with acute cervical spinal cord injury: a randomized, double-blind, multicentre, placebo-controlled, phase 2b trial","volume":"24","author":"N Weidner","year":"2025","journal-title":"Lancet Neurol"},{"issue":"21","key":"ref18","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1089\/neu.2013.2909","article-title":"Analysis of recruitment and outcomes in the phase I\/IIa Cethrin clinical trial for acute spinal cord injury","volume":"30","author":"L McKerracher","year":"2013","journal-title":"J Neurotrauma"},{"issue":"12","key":"ref19","doi-asserted-by":"publisher","first-page":"2580","DOI":"10.1007\/s00586-012-2213-3","article-title":"Neuroprotective therapy using granulocyte colony-stimulating factor for acute spinal cord injury: a phase I\/IIa clinical trial","volume":"21","author":"H Takahashi","year":"2012","journal-title":"Eur Spine J"},{"issue":"03","key":"ref20","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1097\/BRS.0000000000000121","article-title":"Multicenter prospective nonrandomized controlled clinical trial to prove neurotherapeutic effects of G-CSF for acute spinal cord injury","volume":"39","author":"T Inada","year":"2014","journal-title":"Spine"},{"issue":"03","key":"ref21","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1093\/brain\/awab466","article-title":"Randomized trial of granulocyte colony-stimulating factor for spinal cord injury","volume":"144","author":"M Koda","year":"2021","journal-title":"Brain"},{"issue":"11","key":"ref22","doi-asserted-by":"publisher","first-page":"4513","DOI":"10.1096\/fj.10-159780","article-title":"Polylaminin, a polymeric form of laminin, promotes regeneration after spinal cord injury","volume":"24","author":"K Menezes","year":"2010","journal-title":"FASEB J"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1592687","DOI":"10.3389\/fvets.2025.1592687","article-title":"A laminin-based therapy for dogs with chronic spinal cord injury: promising results of a longitudinal trial","volume":"12","author":"C M Chize","year":"2025","journal-title":"Front Vet Sci"},{"issue":"01","key":"ref25","doi-asserted-by":"publisher","first-page":"e40","DOI":"10.1212\/WNL.0000000000007718","article-title":"Outcome heterogeneity and bias in acute experimental spinal cord injury: A meta-analysis","volume":"93","author":"R Watzlawick","year":"2019","journal-title":"Neurology"},{"issue":"01","key":"ref26","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/S1474-4422(24)00482-4","article-title":"Progress and future directions in spinal cord injury trials","volume":"24","author":"K M Pedro","year":"2025","journal-title":"Lancet Neurol"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1394","DOI":"10.1093\/brain\/awu038","article-title":"Altering spinal cord excitability enables voluntary movements after chronic complete paralysis in humans","volume":"137","author":"C A Angeli","year":"2014","journal-title":"Brain"}],"container-title":["Arquivos de Neuro-Psiquiatria"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0046-1827054.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:56:48Z","timestamp":1791363408000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0046-1827054"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":26,"journal-issue":{"issue":"08","published-online":{"date-parts":[[2026,5,12]]},"published-print":{"date-parts":[[2026,8]]}},"alternative-id":["s00461827054"],"URL":"https:\/\/doi.org\/10.1055\/s-0046-1827054","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0004-282X","1678-4227"],"issn-type":[{"value":"0004-282X","type":"print"},{"value":"1678-4227","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]}}}