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Immunol."],"abstract":"<jats:p><jats:italic>Tn<\/jats:italic>P is a family of patented synthetic peptides which is in a preclinical development stage with valuable potential therapeutic indication for multiple sclerosis (MS), an autoimmune demyelinating disease of the central nervous system (CNS). The use of a preclinical animal model, such as experimental autoimmune encephalomyelitis (EAE) has deepened our knowledge of the immunomodulatory functions of <jats:italic>Tn<\/jats:italic>P as a drug. We have shown that <jats:italic>Tn<\/jats:italic>P possesses a disease suppressive function in EAE, ameliorating disease severity by 40% and suppressing the accumulation of T helper (Th)1- and Th17-producing lymphocytes (by 55% and 60%, respectively) in CNS along with activated microglia\/macrophages populations (by 33% and 50%, respectively), and also conferred a protective effect anticipating the remyelination process to day 66 compared to day 83 of untreated cuprizone-mice. Here we expanded our knowledge about its effects compared with current first-line disease-modifying therapies (DMT). We demonstrated that prophylactic treatment with <jats:italic>Tn<\/jats:italic>P generated similar protection to betaseron (30%) or was more effective than glatiramer (44% versus 6%) or fingolimod (50% versus 19%) against the development of clinical symptoms. Although <jats:italic>Tn<\/jats:italic>P controlled the leukocyte infiltration (87% versus 82%) into demyelinated areas of the spinal cord in the same way as betaseron and fingolimod, it was more effective (72% to 78% decrease) in the long-term control of neuronal degeneration compared to them. Also, when compared to glatiramer, <jats:italic>Tn<\/jats:italic>P was more efficient in reversing leukocytes infiltration into the spinal cord (55% versus 24%), as well as induced a higher percentage of regulatory cells in spleen (2.9-fold versus 2.3-fold increase over vehicle-treated EAE mice) an in the spinal cord (8-fold versus 6-fold increase over vehicle-treated EAE mice). This specialized <jats:italic>Tn<\/jats:italic>P profile for inducing immune tolerance and neuronal regeneration has significant therapeutic potential for the treatment of MS and other autoimmune diseases.<\/jats:p>","DOI":"10.3389\/fimmu.2022.857692","type":"journal-article","created":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T06:28:24Z","timestamp":1648535304000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["TnP Peptide Suppresses Experimental Autoimmune Encephalomyelitis (EAE) in a Preclinical Mouse Model"],"prefix":"10.3389","volume":"13","author":[{"given":"Carla","family":"Lima","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adolfo Luis Almeida","family":"Maleski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jefferson Thiago Gon\u00e7alves","family":"Bernardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitor Cataldi","family":"Zelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evilin Naname","family":"Komegae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Lopes-Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2021.02.019","article-title":"PepTherDia: Database and Structural Composition Analysis of Approved Peptide Therapeutics and Diagnostics","volume":"26","author":"D\u2019Aloisio","year":"2021","journal-title":"Drug Discov Today"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-020-00135-8","article-title":"Trends in Peptide Drug Discovery","volume":"20","author":"Muttenthaler","year":"2021","journal-title":"Nat Rev Drug Discov"},{"key":"B3","article-title":"PI0602885-3a2: Pept\u00eddeos C\u00edclicos Anti-Inflamat\u00f3rios E Anti-Al\u00e9rgicos","author":"Lopes-Ferreira","year":"2019"},{"key":"B4","doi-asserted-by":"publisher","first-page":"e0171796","DOI":"10.1371\/journal.pone.0171796","article-title":"Multiple Functional Therapeutic Effects of TnP, a Small Stable Synthetic Peptide Derived From Fish Venom in a Mouse Model of Multiple Sclerosis","volume":"12","author":"Komegae","year":"2017","journal-title":"PloS One"},{"key":"B5","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.toxrep.2020.12.004","article-title":"Early Preclinical Screening Using Zebrafish (Danio Rerio) Reveals the Safety of the Candidate Anti-Inflammatory Therapeutic Agent TnP","volume":"8","author":"Batista-Filho","year":"2021","journal-title":"Toxicol Rep"},{"key":"B6","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1186\/s12883-021-02347-w","article-title":"Clinical Characteristics of Middle-Aged and Older Patients With MS Treated With Interferon Beta-1b: Post-Hoc Analysis of a 2-Year, Prospective, International, Observational Study","volume":"21","author":"Patti","year":"2021","journal-title":"BMC Neurol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000275230.20635.72","article-title":"Experimental Models of Neuroprotection Relevant to Multiple Sclerosis","volume":"68","author":"Yong","year":"2007","journal-title":"Neurology"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.45.7.1268","article-title":"Copolymer 1 Reduces Relapse Rate and Improves Disability in Relapsing-Remitting Multiple Sclerosis: Results of a Phase III Multicenter, Double-Blind Placebo-Controlled Trial. 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