{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:59:00Z","timestamp":1785437940547,"version":"3.56.0"},"posted":{"date-parts":[[2026,3,9]]},"group-title":"Pharmacology and Toxicology","reference-count":20,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["R01HL167969"],"award-info":[{"award-number":["R01HL167969"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/03sabpy05","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Neurodon Corporation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Progressive cardiomyopathy is the leading cause of death in Duchenne muscular dystrophy (DMD). Dysregulation of calcium handling has been implicated in cardiomyopathy progression in DMD. Here we describe a therapeutic approach to improve calcium homeostasis in a mouse model of DMD using the novel therapeutic NDC-1171, which is a positive allosteric modulator of the sarcoplasmic\/endoplasmic reticulum calcium ATPase (SERCA) pump. We synthesized NDC-1171 and treated 4-week-old D2.\n                  <jats:italic>mdx<\/jats:italic>\n                  mice (n=9) via oral gavage. A group of D2.\n                  <jats:italic>mdx<\/jats:italic>\n                  mice (n=9) and a group of DBA\/2J mice (n=9; background strain) received a vehicle on the same schedule. We used ultrasound to assess left ventricular function, followed by a treadmill exhaustion test and a 4-paw grip strength test to assess skeletal muscle function. NDC-1171 attenuated cardiac functional decline in D2.\n                  <jats:italic>mdx<\/jats:italic>\n                  mice. At 16 weeks of age, left ventricular ejection fraction (LVEF) was significantly preserved in mice treated with NDC-1171 (57.7\u25a1\u00b1\u25a10.5%) compared to mice treated with a vehicle (50.7\u25a1\u00b1\u25a10.9%,\n                  <jats:italic>p<\/jats:italic>\n                  \u25a1&lt;\u25a10.05), though remained lower than background strain controls (62.4\u25a1\u00b1\u25a10.6%). In contrast, functional behavior testing revealed no significant improvement in skeletal muscle function with treatment. These data suggest that treatment with the SERCA pump modulator NDC-1171 helps preserve cardiac function in a murine model of DMD, even as skeletal muscle function was impaired. Future work will be needed to determine if the benefits of this novel SERCA activator translate to large animal and clinical studies, but these initial results are promising and could help guide development of future treatments for pediatric patients with muscular dystrophy.\n                <\/jats:p>","DOI":"10.64898\/2026.03.05.709950","type":"posted-content","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T20:15:23Z","timestamp":1773087323000},"source":"Crossref","is-referenced-by-count":0,"title":["Positive allosteric modulator of SERCA pump NDC-1171 attenuates cardiac functional decline in mouse model of Duchenne muscular dystrophy"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2874-5171","authenticated-orcid":false,"given":"Niharika","family":"Narra","sequence":"first","affiliation":[{"name":"Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa M.","family":"Richards","sequence":"additional","affiliation":[{"name":"Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conner C.","family":"Earl","sequence":"additional","affiliation":[{"name":"Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA"},{"name":"Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail D.","family":"Cox","sequence":"additional","affiliation":[{"name":"Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell","family":"Dahl","sequence":"additional","affiliation":[{"name":"Neurodon Corporation., Crown Point, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy A.","family":"Koss","sequence":"additional","affiliation":[{"name":"Animal Behavior Core, Purdue University, West Lafayette, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8883-7953","authenticated-orcid":false,"given":"Craig J.","family":"Goergen","sequence":"additional","affiliation":[{"name":"Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, 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