{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T17:08:45Z","timestamp":1784740125846,"version":"3.55.0"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"15","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2024,10,8]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>\n              Calmodulinopathies are rare inherited arrhythmia syndromes caused by dominant heterozygous variants in\n              <jats:italic toggle=\"yes\">CALM1<\/jats:italic>\n              ,\n              <jats:italic toggle=\"yes\">CALM2<\/jats:italic>\n              , or\n              <jats:italic toggle=\"yes\">CALM3<\/jats:italic>\n              , which each encode the identical CaM (calmodulin) protein. We hypothesized that antisense oligonucleotide (ASO)\u2013mediated depletion of an affected calmodulin gene would ameliorate disease manifestations, whereas the other 2 calmodulin genes would preserve CaM level and function.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>\n              We tested this hypothesis using human induced pluripotent stem cell\u2013derived cardiomyocyte and mouse models of\n              <jats:italic toggle=\"yes\">CALM1<\/jats:italic>\n              pathogenic variants.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              Human\n              <jats:italic toggle=\"yes\">CALM1<\/jats:italic>\n              <jats:sup>\n                <jats:italic toggle=\"yes\">F142L\/+<\/jats:italic>\n              <\/jats:sup>\n              induced pluripotent stem cell\u2013derived cardiomyocytes exhibited prolonged action potentials, modeling congenital long QT syndrome. CALM1 knockout or CALM1-depleting ASOs did not alter CaM protein level and normalized repolarization duration of\n              <jats:italic toggle=\"yes\">CALM1<\/jats:italic>\n              <jats:sup>\n                <jats:italic toggle=\"yes\">F142L\/+<\/jats:italic>\n              <\/jats:sup>\n              induced pluripotent stem cell\u2013derived cardiomyocytes. Similarly, an ASO targeting murine\n              <jats:italic toggle=\"yes\">Calm1<\/jats:italic>\n              depleted\n              <jats:italic toggle=\"yes\">Calm1<\/jats:italic>\n              transcript without affecting CaM protein level. This ASO alleviated drug-induced bidirectional ventricular tachycardia in\n              <jats:italic toggle=\"yes\">Calm1<\/jats:italic>\n              <jats:sup>\n                <jats:italic toggle=\"yes\">N98S\/+<\/jats:italic>\n              <\/jats:sup>\n              mice without a deleterious effect on cardiac electrical or contractile function.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>These results provide proof of concept that ASOs targeting individual calmodulin genes are potentially effective and safe therapies for calmodulinopathies.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.123.068111","type":"journal-article","created":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T09:00:33Z","timestamp":1724058033000},"page":"1199-1210","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":22,"title":["Antisense Oligonucleotide Therapy for Calmodulinopathy"],"prefix":"10.1161","volume":"150","author":[{"given":"Raul H.","family":"Bortolin","sequence":"first","affiliation":[{"name":"Department of Cardiology (R.H.B., F.N., C.P., M.A.T., M.P., M.E.S., P.W., J.C., F.L., C.L., P.B., E.M.K., D.Y., N.P., T.S., Q.M., D.J.A., V.J.B., W.T.P.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farina","family":"Nawar","sequence":"additional","affiliation":[{"name":"Department of Cardiology (R.H.B., F.N., C.P., M.A.T., M.P., M.E.S., P.W., J.C., F.L., C.L., P.B., E.M.K., D.Y., N.P., T.S., Q.M., D.J.A., V.J.B., 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