{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:52:06Z","timestamp":1791301926792,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Spinal muscular atrophy (SMA) is caused by deletions or mutations in the\n                      <jats:italic>survival motor neuron 1<\/jats:italic>\n                      (\n                      <jats:italic>SMN1<\/jats:italic>\n                      ) gene and subsequent reduction in the expression of survival motor neuron (SMN) protein. The disease is characterized by degeneration of \u03b1 motor neurons and subsequent muscle atrophy. Postnatal disease modifying therapies improve outcomes yet fall short of a cure. We have investigated a prenatal therapeutic strategy using the SMN\u03947 mouse model of SMA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A risdiplam\u2010like compound was administrated by oral gavage to pregnant mice with treatment initiated mid\u2010gestation and halted on day of birth. Reproductive metrics, liver toxicology, and immune function were assessed in the pregnant dams during gestation and post\u2010birth. Progeny were monitored phenotypically, and pathological hallmarks of SMA were investigated including, but not limited to motor neuron, neuromuscular junction, and muscle health.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Maternal\u2010fetal drug transfer was safe for the pregnant dam and substantially increased weight, motor function, and survival of severe SMA mice. It also rescued and maintained myofiber area. Presynaptic components of the neuromuscular junction were marginally improved in SMN\u03947 pups, whereas postsynaptic endplate size was increased following prenatal risdiplam treatment. Motor neuron pathology was not fully rescued by prenatal exposure to SMN protein, likely because of the lack of continued postnatal intervention. By restricting risdiplam treatment to the prenatal period, we have isolated and assessed therapeutic effects attributable solely to embryo exposure of the therapeutic.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Our efforts demonstrate a combination of prenatal and postnatal therapy must be used for optimum therapeutic outcomes in the treatment of patients with SMA. ANN NEUROL 2026;100:584\u2013599<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.78302","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T04:31:29Z","timestamp":1784176289000},"page":"584-599","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Maternal\u2010Fetal Administration of Risdiplam Partially Rescues the\n                    <scp>SMN\u03947<\/scp>\n                    Mouse Model of Spinal Muscular Atrophy"],"prefix":"10.1002","volume":"100","author":[{"given":"Emma R.","family":"Sutton","sequence":"first","affiliation":[{"name":"Regenerative Medicine Program The Ottawa Hospital Research Institute  Ottawa Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariane","family":"Beauvais","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Program The Ottawa Hospital Research Institute  Ottawa Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Yaworski","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Program The Ottawa Hospital Research Institute  Ottawa Canada"},{"name":"Department of Cellular and Molecular Medicine University of Ottawa  Ottawa Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugh J.","family":"McMillan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children's Hospital of Eastern Ontario University of Ottawa  Ottawa Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9239-7310","authenticated-orcid":false,"given":"Rashmi","family":"Kothary","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Program The Ottawa Hospital Research Institute  Ottawa Canada"},{"name":"Department of Cellular and Molecular Medicine University of Ottawa  Ottawa Canada"},{"name":"Department of Medicine University of Ottawa  Ottawa Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90460-3"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2017.46"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2504911"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.192835"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI124120"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24864"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI57291"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.27853"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01867-3"},{"key":"e_1_2_9_11_1","unstructured":"Institute for Quality and Efficiency in Health Care (IQWiG).Newborn screening for 5q\u2010linked spinal muscular atrophy: IQWiG reports \u2013 commission No. S18\u201002. 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