{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T20:35:41Z","timestamp":1768336541805,"version":"3.49.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"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. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder that requires novel therapeutic approaches beyond dystrophin restoration. Myostatin, a negative regulator of muscle growth, has emerged as a promising target to enhance muscle mass and function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We evaluated the efficacy of an orally administered\n                      <jats:italic>Lactobacillus casei<\/jats:italic>\n                      strain expressing a modified human myostatin protein (BLS-M22), in 32-week-old\n                      <jats:italic>mdx<\/jats:italic>\n                      mice. Animals received BLS-M22 or control (\n                      <jats:italic>L. casei<\/jats:italic>\n                      -pgsA) for 8\u202fweeks (control group\u202f=\u202f8, treated group\u202f=\u202f7) and 12\u202fweeks (control group\u202f=\u202f8, treated group\u202f=\u202f9).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>BLS-M22 elicited a robust systemic anti-myostatin antibody response and significantly reduced serum creatine kinase levels, indicating attenuated muscle damage. Treated mice showed improved endurance in rotarod performance. However, no significant differences were observed in body weight, muscle fiber cross-sectional area, or fibrosis, reflecting the limited regenerative capacity at an advanced disease stage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study demonstrates that myostatin inhibition with orally administered\n                      <jats:italic>L. casei<\/jats:italic>\n                      expressing a modified human myostatin protein confers functional benefits even in advanced DMD, while highlighting its therapeutic limitations without concomitant dystrophin restoration. As a cost-effective, non-invasive, and immunologically distinct platform, this system holds translational potential not only for DMD but also for broader applications in sarcopenia and metabolic disorders.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2025.1693484","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T13:55:17Z","timestamp":1768312517000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Myostatin inhibition with orally administered Lactobacillus casei expressing a modified human myostatin protein: functional benefits and translational potential in advanced Duchenne muscular dystrophy"],"prefix":"10.3389","volume":"16","author":[{"given":"Jiwon","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ju-A","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yena","family":"Oh","sequence":"additional","affiliation":[{"name":"MOA Life Plus Co. Ltd.","place":["Yongin-si, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kwang","family":"Kim","sequence":"additional","affiliation":[{"name":"MOA Life Plus Co. Ltd.","place":["Yongin-si, Republic of Korea"]},{"name":"Future & Tech Corp.","place":["Daejeon, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeehun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,13]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1007\/BF00275183","article-title":"Duchenne muscular dystrophy: pathogenetic aspects and genetic prevention","volume":"66","author":"Moser","year":"1984","journal-title":"Hum Genet"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1186\/s13023-021-01862-w","article-title":"The clinical course of Duchenne muscular dystrophy in the corticosteroid treatment era: a systematic literature review","volume":"16","author":"Szabo","year":"2021","journal-title":"Orphanet J Rare Dis"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1177\/0009922810378738","article-title":"Review of Duchenne muscular dystrophy (DMD) for the pediatricians in the community","volume":"49","author":"Verma","year":"2010","journal-title":"Clin Pediatr Phila"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1212\/WNL.0000000000002891","article-title":"DMD genotypes and loss of ambulation in the CINRG Duchenne natural history study","volume":"87","author":"Bello","year":"2016","journal-title":"Neurology"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/S1474-4422(18)30025-5","article-title":"Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management","volume":"17","author":"Birnkrant","year":"2018","journal-title":"Lancet Neurol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/S1474-4422(18)30024-3","article-title":"Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management","volume":"17","author":"Birnkrant","year":"2018","journal-title":"Lancet Neurol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1186\/s13023-025-03906-x","article-title":"Epidemiology, disease burden and costs of Duchenne muscular dystrophy in Germany: an observational, retrospective health claims data analysis","volume":"20","author":"Diesing","year":"2025","journal-title":"Orphanet J Rare Dis"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/387083a0","article-title":"Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member","volume":"387","author":"Mcpherron","year":"1997","journal-title":"Nature"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"12457","DOI":"10.1073\/pnas.94.23.12457","article-title":"Double muscling in cattle due to mutations in the myostatin gene","volume":"94","author":"Mcpherron","year":"1997","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1002\/ana.10385","article-title":"Loss of myostatin attenuates severity of muscular dystrophy in mdx mice","volume":"52","author":"Wagner","year":"2002","journal-title":"Ann Neurol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1016\/s0006-291x(02)02953-4","article-title":"Inhibition of myostatin in adult mice increases skeletal muscle mass and strength","volume":"300","author":"Whittemore","year":"2003","journal-title":"Biochem Biophys Res Commun"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1486","DOI":"10.1126\/science.1069525","article-title":"Induction of cachexia in mice by systemically administered myostatin","volume":"296","author":"Zimmers","year":"2002","journal-title":"Science"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"948","DOI":"10.1016\/S2213-8587(15)00298-3","article-title":"Myostatin antibody (LY2495655) in older weak fallers: a proof-of-concept, randomised, phase 2 trial","volume":"3","author":"Becker","year":"2015","journal-title":"Lancet Diabetes Endocrinol"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1093\/gerona\/glad033","article-title":"Challenges and future prospects of targeting myostatin\/activin a Signaling to treat diseases of muscle loss and metabolic dysfunction","volume":"78","author":"Lee","year":"2023","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1002\/ana.21338","article-title":"A phase I\/IItrial of MYO-029 in adult subjects with muscular dystrophy","volume":"63","author":"Wagner","year":"2008","journal-title":"Ann Neurol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1535","DOI":"10.1007\/s11010-024-05120-y","article-title":"Therapeutic applications and challenges in myostatin inhibition for enhanced skeletal muscle mass and functions","volume":"480","author":"Wetzlich","year":"2025","journal-title":"Mol Cell Biochem"},{"key":"ref17","first-page":"62","article-title":"A phase 2 randomized study investigating the efficacy and safety of myostatin antibody LY2495655 versus placebo in patients undergoing elective total hip arthroplasty","volume":"5","author":"Woodhouse","year":"2016","journal-title":"J Frailty Aging"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"9059","DOI":"10.3390\/ijms23169059","article-title":"A new method of myostatin inhibition in mice via Oral Administration of Lactobacillus casei expressing modified myostatin protein, BLS-M22","volume":"23","author":"Sung","year":"2022","journal-title":"Int J Mol Sci"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"4079","DOI":"10.1128\/JVI.80.8.4079-4087.2006","article-title":"Mucosal immunization with surface-displayed severe acute respiratory syndrome coronavirus spike protein on Lactobacillus casei induces neutralizing antibodies in mice","volume":"80","author":"Lee","year":"2006","journal-title":"J Virol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1038\/76494","article-title":"Surface-displayed viral antigens on Salmonella carrier vaccine","volume":"18","author":"Lee","year":"2000","journal-title":"Nat Biotechnol"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1182\/blood-2003-01-0110","article-title":"Immunogenicity and protective efficacy of orally administered recombinant Lactococcus lactis expressing surface-bound HIV env","volume":"102","author":"Xin","year":"2003","journal-title":"Blood"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1002\/mus.28073","article-title":"Longitudinal data of serum creatine kinase levels and motor, pulmonary, and cardiac functions in 337 patients with Duchenne muscular dystrophy","volume":"69","author":"Awano","year":"2024","journal-title":"Muscle Nerve"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/0022-510X(91)90068-I","article-title":"Serum creatine-kinase (CK) and pyruvate-kinase (PK) activities in Duchenne (DMD) as compared with Becker (BMD) muscular dystrophy","volume":"102","author":"Zatz","year":"1991","journal-title":"J Neurol Sci"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"e51303","DOI":"10.3791\/51303-v","article-title":"Assessing functional performance in the mdx mouse model","volume":"85","author":"Aartsma-Rus","year":"2014","journal-title":"J Vis Exp"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1002\/mus.21211","article-title":"Preclinical drug trials in the mdx mouse: assessment of reliable and sensitive outcome measures","volume":"39","author":"Spurney","year":"2009","journal-title":"Muscle Nerve"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1172\/JCI7866","article-title":"Aminoglycoside antibiotics restore dystrophin function to skeletal muscles of mdx mice","volume":"104","author":"Barton-Davis","year":"1999","journal-title":"J Clin Invest"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1083\/jcb.200108071","article-title":"Muscle-specific expression of insulin-like growth factor I counters muscle decline in mdx mice","volume":"157","author":"Barton","year":"2002","journal-title":"J Cell Biol"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.1038\/nm1202-1355","article-title":"Sizing up muscular dystrophy","volume":"8","author":"Zammit","year":"2002","journal-title":"Nat Med"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"876078","DOI":"10.3389\/fphys.2022.876078","article-title":"Myostatin and its regulation: a comprehensive review of myostatin inhibiting strategies","volume":"13","author":"Baig","year":"2022","journal-title":"Front Physiol"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"74","DOI":"10.3390\/biomedicines6030074","article-title":"Targeting TGF\u03b2 Signaling to address fibrosis using antisense oligonucleotides","volume":"6","author":"March","year":"2018","journal-title":"Biomedicine"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1859","DOI":"10.1038\/s41467-017-01486-4","article-title":"Downregulation of myostatin pathway in neuromuscular diseases may explain challenges of anti-myostatin therapeutic approaches","volume":"8","author":"Mariot","year":"2017","journal-title":"Nat Commun"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/j.nmd.2004.10.018","article-title":"The function of myostatin and strategies of myostatin blockade-new hope for therapies aimed at promoting growth of skeletal muscle","volume":"15","author":"Patel","year":"2005","journal-title":"Neuromuscul Disord"},{"key":"ref33","first-page":"230","article-title":"Molecular mechanisms involving IGF-1 and myostatin to induce muscle hypertrophy as a therapeutic strategy for Duchenne muscular dystrophy","volume":"24","author":"Patel","year":"2005","journal-title":"Acta Myol"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1016\/j.nmd.2020.05.002","article-title":"Randomized phase 2 trial and open-label extension of domagrozumab in Duchenne muscular dystrophy","volume":"30","author":"Wagner","year":"2020","journal-title":"Neuromuscul Disord"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/1471-2377-3-7","article-title":"Deflazacort for the treatment of Duchenne dystrophy: a systematic review","volume":"3","author":"Campbell","year":"2003","journal-title":"BMC Neurol"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1016\/j.nurt.2008.08.013","article-title":"Approaching a new age in Duchenne muscular dystrophy treatment","volume":"5","author":"Wagner","year":"2008","journal-title":"Neurotherapeutics"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1007\/s40120-023-00570-w","article-title":"The clinical development of Taldefgrobep alfa: an anti-myostatin adnectin for the treatment of Duchenne muscular dystrophy","volume":"13","author":"Muntoni","year":"2024","journal-title":"Neurol Ther"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"3091","DOI":"10.1093\/hmg\/ddz125","article-title":"Functional muscle recovery following dystrophin and myostatin exon splice modulation in aged mdx mice","volume":"28","author":"Lu-Nguyen","year":"2019","journal-title":"Hum Mol Genet"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.omtn.2016.11.009","article-title":"Systemic antisense therapeutics for dystrophin and myostatin exon splice modulation improve muscle pathology of adult mdx mice","volume":"6","author":"Lu-Nguyen","year":"2017","journal-title":"Mol Ther Nucleic Acids"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"1341","DOI":"10.1038\/mt.2015.88","article-title":"Combination antisense treatment for destructive exon skipping of myostatin and open reading frame rescue of dystrophin in neonatal mdx mice","volume":"23","author":"Lu-Nguyen","year":"2015","journal-title":"Mol Ther"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"273","DOI":"10.3390\/ijms251910273","article-title":"Taldefgrobep alfa and the phase 3 RESILIENT trial in spinal muscular atrophy","volume":"25","author":"Servais","year":"2024","journal-title":"Int J Mol Sci"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"1988","DOI":"10.1111\/jgs.14927","article-title":"Treatment of sarcopenia with bimagrumab: results from a phase II, randomized, controlled, proof-of-concept study","volume":"65","author":"Rooks","year":"2017","journal-title":"J Am Geriatr Soc"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"2160","DOI":"10.1038\/s41598-021-81669-8","article-title":"Novel myostatin-specific antibody enhances muscle strength in muscle disease models","volume":"11","author":"Muramatsu","year":"2021","journal-title":"Sci Rep"},{"key":"ref44","doi-asserted-by":"publisher","DOI":"10.17632\/k8cwxkfb92.1","article-title":"Dataset for old mdx mice with BLS-M22","author":"Lee","year":"2025","journal-title":"Mendeley Data, V1"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1007\/s00415-016-8379-6","article-title":"Reduced serum myostatin concentrations associated with genetic muscle disease progression","volume":"264","author":"Burch","year":"2021","journal-title":"J Neurol"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2025.1693484\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T13:55:20Z","timestamp":1768312520000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2025.1693484\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,13]]},"references-count":45,"alternative-id":["10.3389\/fneur.2025.1693484"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2025.1693484","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,13]]},"article-number":"1693484"}}