Time Release Ion Matrix Regenerates Dystrophic Skeletal Muscle

Time Release Ion Matrix Regenerates Dystrophic Skeletal Muscle | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Time Release Ion Matrix Regenerates Dystrophic Skeletal Muscle Aaron Morton, Jacob Kendra, Alexandra Naman, Rebekah Blatt, Richard Brow, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5968078/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract A time-release ion matrix (TRIM) restores damaged tissue following injury through local ion release to stimulate regenerative gene expression. Here we report the use of CoO-TRIM, an FDA-designated Rare Pediatric Disease Drug, to restore muscle function and structure in the context of debilitating muscle disease. We demonstrate in an established animal model of Duchenne Muscular Dystrophy (DMD), the D2.mdx mouse, that tibialis anterior (TA) muscles receiving a single injection of CoO-TRIM exhibit greater active force, myofiber size and regeneration through 70 days post-treatment compared to D2.mdx receiving vehicle alone. TRIM promoted upregulation of pro-angiogenic growth factor (vascular endothelial growth factor) and increased muscle microvasculature. These findings indicate that CoO-TRIM stimulates growth factors to promote the restoration of muscle structure and function of severely dystrophic mice in vivo without toxicity. We conclude that CoO-TRIM is a first-in-class therapeutic compound to combat soft tissue disease by restoring tissue integrity. Moreover, this novel treatment strategy could benefit both early and late-stage DMD patients. Biological sciences/Biotechnology Biological sciences/Biotechnology/Biomaterials Biological sciences/Biotechnology/Biomaterials/Drug delivery Angiogenesis Bioactive Glass CoO-TRIM Muscular Dystrophy Regenerative Medicine Skeletal Muscle Time Release Ion Matrix VEGF Full Text Additional Declarations Competing interest reported. The work described in this article is covered by patent application no. WO2023034523A1. A.B.M., S.S.S., and R.K.B. are co-inventors of CoO-TRIM. A.B.M. is a co-founder and shareholder of Bioramics, LLC, shareholder of the licensing company DystropHix, LLC. CoO-TRIM has received designation as an Orphan Disease Drug and Rare Pediatric Disease Drug from the FDA. Supplementary Files SupplementaryFiguresTRIMSciRep.pdf Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5968078","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":422752195,"identity":"9c051645-a993-4559-a627-2c4e219e9957","order_by":0,"name":"Aaron Morton","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAr0lEQVRIiWNgGAWjYBADOSjNTKT6AwwMxjwka0nsIVoL/7TDxz5/qLiTvp/9dJoEQ4V1YgMhLRK305JnHDjzLLeHJ3ebBMOZdMJaGG7nGDMcbDuc28MA1MLYdpiwFnmolnQe/rdALf+I0GIA1ZLAIwGypYEILYZAvzCcOXPYsOfG280WCcfSjQlqkbudfJihouKwPHt/7sYbH2qsZQlqQQUJpCkfBaNgFIyCUYALAAAnpEBZmM711gAAAABJRU5ErkJggg==","orcid":"","institution":"Texas A\u0026M University","correspondingAuthor":true,"prefix":"","firstName":"Aaron","middleName":"","lastName":"Morton","suffix":""},{"id":422752196,"identity":"e2004800-d9b1-49bc-96fc-8a94839dc82f","order_by":1,"name":"Jacob Kendra","email":"","orcid":"","institution":"Texas A\u0026M University","correspondingAuthor":false,"prefix":"","firstName":"Jacob","middleName":"","lastName":"Kendra","suffix":""},{"id":422752197,"identity":"07ec6b88-c9ab-4abd-bf73-343fc03fe19c","order_by":2,"name":"Alexandra Naman","email":"","orcid":"","institution":"Texas A\u0026M University","correspondingAuthor":false,"prefix":"","firstName":"Alexandra","middleName":"","lastName":"Naman","suffix":""},{"id":422752198,"identity":"4e41127e-411d-41ba-89d9-9226c90f38cf","order_by":3,"name":"Rebekah Blatt","email":"","orcid":"","institution":"Missouri University of Science \u0026 Technology","correspondingAuthor":false,"prefix":"","firstName":"Rebekah","middleName":"","lastName":"Blatt","suffix":""},{"id":422752199,"identity":"2be5532e-94c3-4f9a-8957-eba40a0ba3b6","order_by":4,"name":"Richard Brow","email":"","orcid":"","institution":"Missouri University of Science \u0026 Technology","correspondingAuthor":false,"prefix":"","firstName":"Richard","middleName":"","lastName":"Brow","suffix":""},{"id":422752200,"identity":"cf0e5a59-4549-4b95-8d6e-4b3a031a2188","order_by":5,"name":"Steven Segal","email":"","orcid":"","institution":"University of Missouri","correspondingAuthor":false,"prefix":"","firstName":"Steven","middleName":"","lastName":"Segal","suffix":""},{"id":422752202,"identity":"c46a9c82-1bf7-4b13-a0c3-8f460aa9c71d","order_by":6,"name":"Yava Jones-Hall","email":"","orcid":"","institution":"Texas A\u0026M University","correspondingAuthor":false,"prefix":"","firstName":"Yava","middleName":"","lastName":"Jones-Hall","suffix":""},{"id":422752203,"identity":"6bb28918-b777-43e4-a5a4-78ef1143575d","order_by":7,"name":"Carla Zingariello","email":"","orcid":"","institution":"University of Florida","correspondingAuthor":false,"prefix":"","firstName":"Carla","middleName":"","lastName":"Zingariello","suffix":""}],"badges":[],"createdAt":"2025-02-05 18:38:21","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":true,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-5968078/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5968078/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":81348613,"identity":"361983b5-7756-41e3-b4c3-25148b04ca7e","added_by":"auto","created_at":"2025-04-25 05:39:25","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":7814204,"visible":true,"origin":"","legend":"","description":"","filename":"2.6.25TRIMDystMuscleSciRepmerged.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5968078/v1_covered_21384386-19c4-4eda-8f8c-ab355053c7e7.pdf"},{"id":78881492,"identity":"630d5e2b-c6be-4aa6-a8cd-54ce8b783fc4","added_by":"auto","created_at":"2025-03-20 08:39:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":2113346,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFiguresTRIMSciRep.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5968078/v1/9d4441b2dc80f0c427a791c1.pdf"}],"financialInterests":"Competing interest reported. The work described in this article is covered by patent application no. WO2023034523A1. A.B.M., S.S.S., and R.K.B. are co-inventors of CoO-TRIM. A.B.M. is a co-founder and shareholder of Bioramics, LLC, shareholder of the licensing company DystropHix, LLC. CoO-TRIM has received designation as an Orphan Disease Drug and Rare Pediatric Disease Drug from the FDA.","formattedTitle":"Time Release Ion Matrix Regenerates Dystrophic Skeletal Muscle","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Angiogenesis, Bioactive Glass, CoO-TRIM, Muscular Dystrophy, Regenerative Medicine, Skeletal Muscle, Time Release Ion Matrix, VEGF","lastPublishedDoi":"10.21203/rs.3.rs-5968078/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5968078/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"A time-release ion matrix (TRIM) restores damaged tissue following injury through local ion release to stimulate regenerative gene expression. Here we report the use of CoO-TRIM, an FDA-designated Rare Pediatric Disease Drug, to restore muscle function and structure in the context of debilitating muscle disease. We demonstrate in an established animal model of Duchenne Muscular Dystrophy (DMD), the D2.mdx mouse, that tibialis anterior (TA) muscles receiving a single injection of CoO-TRIM exhibit greater active force, myofiber size and regeneration through 70 days post-treatment compared to D2.mdx receiving vehicle alone. TRIM promoted upregulation of pro-angiogenic growth factor (vascular endothelial growth factor) and increased muscle microvasculature. These findings indicate that CoO-TRIM stimulates growth factors to promote the restoration of muscle structure and function of severely dystrophic mice in vivo without toxicity. We conclude that CoO-TRIM is a first-in-class therapeutic compound to combat soft tissue disease by restoring tissue integrity. Moreover, this novel treatment strategy could benefit both early and late-stage DMD patients.","manuscriptTitle":"Time Release Ion Matrix Regenerates Dystrophic Skeletal Muscle","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-20 08:39:28","doi":"10.21203/rs.3.rs-5968078/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5f5695cb-a094-45fd-9ff2-e3ebcac1fdbc","owner":[],"postedDate":"March 20th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":45060904,"name":"Biological sciences/Biotechnology"},{"id":45060905,"name":"Biological sciences/Biotechnology/Biomaterials"},{"id":45060906,"name":"Biological sciences/Biotechnology/Biomaterials/Drug delivery"}],"tags":[],"updatedAt":"2025-04-25T05:23:08+00:00","versionOfRecord":[],"versionCreatedAt":"2025-03-20 08:39:28","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5968078","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5968078","identity":"rs-5968078","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}