{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:58:24Z","timestamp":1790866704334,"version":"4.1.0"},"reference-count":133,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institutes of Health, National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["T32GM144636"],"award-info":[{"award-number":["T32GM144636"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R21AR075193"],"award-info":[{"award-number":["R21AR075193"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association Research","doi-asserted-by":"publisher","award":["22-1061420"],"award-info":[{"award-number":["22-1061420"]}],"id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association Predoctoral Fellowship","doi-asserted-by":"publisher","award":["25PRE1373209"],"award-info":[{"award-number":["25PRE1373209"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Mutations in the LMNA gene encoding A-type lamins cause multiple muscular dystrophies (LMNA-MD). Lamins are intermediate filaments with three conserved domains: an N-terminal head, a coiled-coil rod, and a C-terminal domain possessing an Ig-like fold. Missense mutations in all three domains can cause LMNA-MD by mechanisms that are not well understood. Currently, there are limited treatments for LMNA-MD beyond symptom management. In this study, our goal was to identify candidate treatments through an in vivo drug repurposing screen using Drosophila models of LMNA-MD that recapitulate aspects of the disease phenotype. Expression of LamC R264Q (Drosophila orthologue of human LMNA R249Q) in fly muscles causes muscle defects and premature death. We fed 1520, mostly FDA\/EMA-approved, drugs to larvae and screened for rescue of lethality. This screen resulted in 68 positive hit drugs that partially restored viability. Molecular fingerprinting clustered a subset of these compounds into six structurally related groups, including L-type voltage-gated calcium channel inhibitors. We tested these inhibitors using multiple fly models expressing different mutant lamins and discovered that only flies expressing amino acid substitutions in the rod domain benefited, supporting a need for personalized treatments. Collectively, our findings support L-type voltage-gated calcium channel blockers as candidate treatments that warrant testing in pre-clinical models.<\/jats:p>","DOI":"10.3390\/ijms27188367","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:23:56Z","timestamp":1790864636000},"page":"8367","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An Unbiased Drug Screen in a Drosophila Model of LMNA-Muscular Dystrophy Identifies Calcium Channel Blockers as Potential Treatments"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1990-4600","authenticated-orcid":false,"given":"Nathaniel P.","family":"Mohar","sequence":"first","affiliation":[{"name":"Interdisciplinary Graduate Program in Genetics, University of Iowa, Iowa City, IA 52242, USA"},{"name":"Department of Biochemistry and Molecular Biology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5396-1090","authenticated-orcid":false,"given":"Brenna A.","family":"Powers","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Benjamin E.","family":"Hinz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Alex R.","family":"Bock","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7736-6696","authenticated-orcid":false,"given":"Hailey","family":"McCoy-Munger","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA"},{"name":"Department of Biomedical Engineering, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"software","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Zachary","family":"Darr","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2498-5437","authenticated-orcid":false,"given":"Maxwell W.","family":"Shumaker","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1779-8417","authenticated-orcid":false,"given":"Alexander T.","family":"Wemmie","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Amya","family":"Saxena","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Lori L.","family":"Wallrath","sequence":"additional","affiliation":[{"name":"Interdisciplinary Graduate Program in Genetics, University of Iowa, Iowa City, IA 52242, USA"},{"name":"Department of Biochemistry and Molecular Biology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, 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