{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:54:08Z","timestamp":1790394848376,"version":"4.1.0"},"reference-count":36,"publisher":"American Society for Clinical Investigation","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,3,9]]},"abstract":"<jats:p>\n                    Spinal muscular atrophy (SMA) is a leading genetic cause of infantile death and is caused by the loss of survival motor neuron-1 (\n                    <jats:italic>SMN1<\/jats:italic>\n                    ). Importantly, a nearly identical gene is present called\n                    <jats:italic>SMN2<\/jats:italic>\n                    ; however, the majority of\n                    <jats:italic>SMN2<\/jats:italic>\n                    -derived transcripts are alternatively spliced and encode a truncated, dysfunctional protein. Recently, several compounds designed to increase SMN protein have entered clinical trials, including antisense oligonucleotides (ASOs), traditional small molecules, and gene therapy. Expanding beyond SMN-centric therapeutics is important, as it is likely that the breadth of the patient spectrum and the inherent complexity of the disease will be difficult to address with a single therapeutic strategy. Several SMN-independent pathways that could impinge upon the SMA phenotype have been examined with varied success. To identify disease-modifying pathways that could serve as stand-alone therapeutic targets or could be used in combination with an SMN-inducing compound, we investigated adeno-associated virus\u2013mediated (AAV-mediated) gene therapy using plastin-3 (\n                    <jats:italic>PLS3<\/jats:italic>\n                    ). Here, we report that AAV9-\n                    <jats:italic>PLS3<\/jats:italic>\n                    extends survival in an intermediate model of SMA mice as well as in a pharmacologically induced model of SMA using a splice-switching ASO that increases SMN production.\n                    <jats:italic>PLS3<\/jats:italic>\n                    coadministration improves the phenotype beyond the ASO, demonstrating the potential utility of combinatorial therapeutics in SMA that target SMN-independent and SMN-dependent pathways.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.89970","type":"journal-article","created":{"date-parts":[[2017,3,8]],"date-time":"2017-03-08T11:01:03Z","timestamp":1488970863000},"source":"Crossref","is-referenced-by-count":62,"title":["Plastin-3 extends survival and reduces severity in mouse models of spinal muscular atrophy"],"prefix":"10.1172","volume":"2","author":[{"given":"Kevin A.","family":"Kaifer","sequence":"first","affiliation":[{"name":"Molecular Pathogeneses and Therapeutics Program,"},{"name":"Bond Life Sciences Center,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2068-4094","authenticated-orcid":true,"given":"Eric","family":"Villal\u00f3n","sequence":"additional","affiliation":[{"name":"Bond Life Sciences Center,"},{"name":"Department of Veterinary Pathobiology, College of Veterinary Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erkan Y.","family":"Osman","sequence":"additional","affiliation":[{"name":"Bond Life Sciences Center,"},{"name":"Department of Veterinary Pathobiology, College of Veterinary Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline J.","family":"Glascock","sequence":"additional","affiliation":[{"name":"Molecular Pathogeneses and Therapeutics Program,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura 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