{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T08:22:25Z","timestamp":1793694145545,"version":"4.5.1"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Polylaminin, an improved form of the natural protein laminin, has been shown to promote axonal regeneration and functional recovery in animal models of acute spinal cord injury (SCI), and is safe and potentially beneficial in humans when administered within the first days after traumatic SCI. This study aimed to evaluate the effect of polylaminin in dogs with chronic SCI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a prospective, longitudinal study in six paraplegic dogs with severe chronic thoracolumbar SCI (T3-L3) caused by trauma (<jats:italic>n<\/jats:italic>\u202f=\u202f2) or disc degeneration (<jats:italic>n<\/jats:italic>\u202f=\u202f4). The study assessed whether gait scores, measured during an extended screening period (at least 4 months), would improve during the follow-up (6 months). Polylaminin was delivered intraspinally at a dose of 1 \u03bcg\/kg, in combination with either glial-derived neurotrophic factor (GDNF; Group 1; <jats:italic>n<\/jats:italic>\u202f=\u202f3) or chondroitinase ABC (Group 2; <jats:italic>n<\/jats:italic>\u202f=\u202f3). Safety was assessed through neurological examinations, blood tests and monitoring of medical complications. Gait analysis was carried out using the Texas Spinal Cord Injury Scale (TSCIS) and the Open Field Scale (OFS), while a linear mixed model was used for statistical analysis. During the screening period, dogs received physiotherapy twice per week and had their gait scored periodically. The first six dogs whose scores had remained stable across three evaluations were enrolled. After owners provided informed consent, dogs were randomly allocated to either treatment group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>No neurological deterioration, serious clinical events or notable deviations in blood tests were observed. The TSCIS average baseline score increased from 2.2 to 3.2 (95% CI: 0.77\u20131.2; <jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.001), while the OFS score increased from 1.5 to 3.1 (95% CI: 1.3\u20131.9; <jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Although the present study could not discriminate between the benefits of the two treatments, our findings suggest that polylaminin, in combination with GDNF or chondroitinase ABC, is a safe and potentially effective treatment, which underscores the relevance of further studies to establish a new approach to improving gait function in dogs with chronic SCI.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fvets.2025.1592687","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T06:33:19Z","timestamp":1755066799000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["A laminin-based therapy for dogs with chronic spinal cord injury: promising results of a longitudinal trial"],"prefix":"10.3389","volume":"12","author":[{"given":"Carolina de Miranda","family":"Chize","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego Gonzales","family":"Vivas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karla","family":"Menezes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max Nascimento","family":"Freire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo Ferreira Pinto","family":"Jiddu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lio Vicente","family":"Gra\u00e7a-Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliel","family":"de Souza-Leite","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo Roberto","family":"Louzada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Coelho-Sampaio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,13]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1136\/vr.d475","article-title":"Designing clinical trials in canine spinal cord injury as a model to translate successful laboratory interventions into clinical practice","volume":"168","author":"Jeffery","year":"2011","journal-title":"Vet Rec"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.tvjl.2012.05.027","article-title":"Intervertebral disc disease in dogs - part 1: a new histological grading scheme for classification of intervertebral disc degeneration in dogs","volume":"195","author":"Bergknut","year":"2013","journal-title":"Vet J"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"107429","DOI":"10.1016\/j.jbc.2024.107429","article-title":"Polymerizing laminins in development, health, and disease","volume":"300","author":"Yurchenco","year":"2024","journal-title":"J Biol Chem"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1042\/EBC20180075","article-title":"Structural biology of laminins","volume":"63","author":"Hohenester","year":"2019","journal-title":"Essays Biochem"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1074\/jbc.275.2.817","article-title":"Self-assembly of laminin induced by acidic pH","volume":"275","author":"Freire","year":"2000","journal-title":"J Biol Chem"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"11714","DOI":"10.1074\/jbc.M709301200","article-title":"Artificial laminin polymers assembled in acidic pH mimic basement membrane organization","volume":"283","author":"Barroso","year":"2008","journal-title":"J Biol Chem"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1146\/annurev.neuro.30.051606.094337","article-title":"Peripheral regeneration","volume":"30","author":"Chen","year":"2007","journal-title":"Annu Rev Neurosci"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"4867","DOI":"10.1242\/jcs.00173","article-title":"Structure of laminin substrate modulates cellular signaling for neuritogenesis","volume":"115","author":"Freire","year":"2002","journal-title":"J Cell Sci"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1002\/jnr.23298","article-title":"Polylaminin recognition by retinal cells","volume":"92","author":"Hochman-Mendez","year":"2014","journal-title":"J Neurosci Res"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"4513","DOI":"10.1096\/fj.10-157628","article-title":"Polylaminin, a polymeric form of laminin, promotes regeneration after spinal cord injury","volume":"24","author":"Menezes","year":"2010","journal-title":"FASEB J"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1101\/2024.02.19.24301010","article-title":"Return of voluntary motor contraction after complete spinal cord injury: a pilot human study on polylaminin","author":"Menezes","year":"2024","journal-title":"med Rxiv"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1016\/j.matbio.2018.02.009","article-title":"Fibrotic scarring following lesions to the central nervous system","volume":"68","author":"Dias","year":"2018","journal-title":"Matrix Biol"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.expneurol.2013.12.024","article-title":"Functional regeneration beyond the glial scar","volume":"253","author":"Cregg","year":"2014","journal-title":"Exp Neurol"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1093\/brain\/awy007","article-title":"Therapeutic efficacy of microtube-embedded chondroitinase ABC in a canine clinical model of spinal cord injury","volume":"141","author":"Hu","year":"2018","journal-title":"Brain"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1038\/s41593-019-0424-1","article-title":"Chondroitinase improves anatomical and functional outcomes after primate spinal cord injury","volume":"22","author":"Rosenzweig","year":"2019","journal-title":"Nat Neurosci"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1038\/s41586-018-0467-6","article-title":"Required growth facilitators propel axon regeneration across complete spinal cord injury","volume":"561","author":"Anderson","year":"2018","journal-title":"Nature"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.1126\/science.adi6412","article-title":"Recovery of walking after paralysis by regenerating characterized neurons to their natural target region","volume":"381","author":"Squair","year":"2023","journal-title":"Science"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.jocn.2021.09.042","article-title":"Modeling chronic cervical spinal cord injury in aged rats for cell therapy studies","volume":"94","author":"Mart\u00edn-L\u00f3pez","year":"2021","journal-title":"J Clin Neurosci"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1617","DOI":"10.2460\/javma.241.12.1617","article-title":"Long-term neurologic outcome of hemilaminectomy and disk fenestration for treatment of dogs with thoracolumbar intervertebral disk herniation: 831 cases (2000\u20132007)","volume":"241","author":"Aikawa","year":"2012","journal-title":"J Am Vet Med Assoc"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"762","DOI":"10.2460\/javma.2003.222.762","article-title":"Long-term functional outcome of dogs with severe injuries of the thoracolumbar spinal cord: 87 cases (1996\u20132001)","volume":"222","author":"Olby","year":"2003","journal-title":"J Am Vet Med Assoc"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"596059","DOI":"10.3389\/fvets.2020.596059","article-title":"Prognostic factors in canine acute intervertebral disc disease","volume":"7","author":"Olby","year":"2020","journal-title":"Front Vet Sci"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1016\/j.ijbiomac.2016.06.030","article-title":"Improvement of proteolytic and oxidative stability of chondroitinase ABC I by cosolvents","volume":"91","author":"Nazari-Robati","year":"2016","journal-title":"Int J Biol Macromol"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.prevetmed.2009.02.016","article-title":"Description and repeatability of a newly developed spinal cord injury scale for dogs","volume":"89","author":"Levine","year":"2009","journal-title":"Prev Vet Med"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1111\/jvim.13657","article-title":"A placebo-controlled, prospective, randomized clinical trial of polyethylene glycol and methylprednisolone sodium succinate in dogs with intervertebral disc herniation","volume":"30","author":"Olby","year":"2016","journal-title":"J Vet Intern Med"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1991","DOI":"10.1089\/neu.2019.6804","article-title":"Comparison of gait assessment scales in dogs with spinal cord injury from intervertebral disc herniation","volume":"37","author":"Olby","year":"2020","journal-title":"J Neurotrauma"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"e11505","DOI":"10.15252\/emmm.201911505","article-title":"Therapeutic repair for spinal cord injury: combinatory approaches to address a multifaceted problem","volume":"12","author":"Griffin","year":"2020","journal-title":"EMBO Mol Med"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"335Y341","DOI":"10.1007\/s11302-005-5435-6","article-title":"Alkaline phosphatases. Structure, substrate specificity and functional relatedness to other members of a large superfamily of enzymes","volume":"2","author":"Mill\u00e1n","year":"2020","journal-title":"Purinergic Signal"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1038\/416636a","article-title":"Chondroitinase ABC promotes functional recovery after spinal cord injury","volume":"416","author":"Bradbury","year":"2002","journal-title":"Nature"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.1016\/j.jcyt.2015.05.012","article-title":"Effect of the combination of mesenchymal stromal cells and chondroitinase ABC on chronic spinal cord injury","volume":"17","author":"Lee","year":"2015","journal-title":"Cytotherapy"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"38S","DOI":"10.1177\/21925682231197404","article-title":"Timing of decompressive surgery in patients with acute spinal cord injury: systematic review update","volume":"14","author":"Fehlings","year":"2024","journal-title":"Global Spine J"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"39","DOI":"10.2147\/SCCAA.S324184","article-title":"Treatment of chronic spinal cord injury in dogs using amniotic membrane-derived stem cells: preliminary results","volume":"14","author":"Orlandin","year":"2021","journal-title":"Stem Cells Cloning"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1186\/s13063-023-07454-2","article-title":"Duroplasty for injured cervical spinal cord with uncontrolled swelling: protocol of the DISCUS randomized controlled trial","volume":"24","author":"Saadoun","year":"2023","journal-title":"Trials"}],"container-title":["Frontiers in Veterinary Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2025.1592687\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T06:33:21Z","timestamp":1755066801000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2025.1592687\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,13]]},"references-count":32,"alternative-id":["10.3389\/fvets.2025.1592687"],"URL":"https:\/\/doi.org\/10.3389\/fvets.2025.1592687","relation":{},"ISSN":["2297-1769"],"issn-type":[{"value":"2297-1769","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,13]]},"article-number":"1592687"}}