{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T19:39:02Z","timestamp":1772221142480,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,7,7]],"date-time":"2021-07-07T00:00:00Z","timestamp":1625616000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Spinal muscular atrophy (SMA) is an inherited lower motor neuron disease. SMA occurs secondary to alterations in the survival motor neuron 1 gene (<jats:italic>SMN1<\/jats:italic>), which is the main driver of SMN protein production. The severity of the disease is determined by the number of copies of the<jats:italic>SMN2<\/jats:italic>gene, which is a homolog to<jats:italic>SMN1<\/jats:italic>but not as efficient in protein production. Three medications have recently been approved for the treatment of SMA. Nusinersen is an intrathecal antisense oligonucleotide that alters<jats:italic>SMN2<\/jats:italic>pre\u2010mRNA, onasemnogene abeparvovec\u2010xioi is an intravenous<jats:italic>SMN1<\/jats:italic>gene replacement therapy, and risdiplam is an oral small molecule splicing modifier of<jats:italic>SMN2<\/jats:italic>. No head\u2010to\u2010head studies have been conducted comparing these medications, so selection of one of these medications for an individual with SMA can be challenging. In this article we outline the efficacy, safety, and other pertinent factors to consider when selecting a therapy for an individual with SMA. The age of the individual and comorbidities, such as liver or kidney disease, help guide treatment choices. All three of these medications are efficacious, and early initiation is critical for obtaining the best outcomes.<\/jats:p>","DOI":"10.1002\/mus.27358","type":"journal-article","created":{"date-parts":[[2021,7,7]],"date-time":"2021-07-07T10:39:13Z","timestamp":1625654353000},"page":"404-412","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Selecting disease\u2010modifying medications in 5q spinal muscular atrophy"],"prefix":"10.1002","volume":"64","author":[{"given":"Michael S.","family":"Cartwright","sequence":"first","affiliation":[{"name":"Department of Neurology Wake Forest School of Medicine Winston\u2010Salem North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suraj","family":"Upadhya","sequence":"additional","affiliation":[{"name":"Department of Neurology Wake Forest School of Medicine Winston\u2010Salem North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,7,7]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90460-3"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2011.134"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi390"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1086\/338627"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.11.6307"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000007742"},{"key":"e_1_2_13_8_1","unstructured":"Spinraza (nusinersen) injection for intrathecal use.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2016\/209531lbl.pdf. Accessed December 8 2020."},{"key":"e_1_2_13_9_1","unstructured":"Zolgensma INN\u2010Onasemnogene abeparvovec.https:\/\/www.avexis.com\/us\/content\/pdf\/prescribing_information.pdf. Accessed December 8 2020."},{"key":"e_1_2_13_10_1","unstructured":"Evrysdi (risdiplam) for oral solution.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2020\/213535s000lbl.pdf. Accessed December 8 2020."},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.18665"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1702752"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000006502"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1706198"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13786"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.8b00741"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.447"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2009.11.014"},{"key":"e_1_2_13_19_1","unstructured":"DubowitzL DubowitzV MercuriE et al. Hammersmith neurological examinations.https:\/\/hammersmith-neuro-exam.com. Accessed December 8 2020."},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-012370877-9.00018-9"},{"key":"e_1_2_13_21_1","unstructured":"Hammersmith Functional Motor Scale Expanded for SMA (HFMSA).http:\/\/columbiasma.org\/docs\/hfmse_2019_manual.pdf. Accessed December 8 2020."},{"key":"e_1_2_13_22_1","unstructured":"MazzoneES MayhewA RamseyD et al. Revised upper limb module for SMA (RULM for SMA).http:\/\/columbiasma.org\/docs\/cme-2010\/rulm-generic-manual-16-dec-2014.pdf. Accessed December 8 2020."},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apmr.2013.01.014"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-017-0831-9"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2019.09.007"},{"key":"e_1_2_13_26_1","unstructured":"Results from the ongoing presymptomatic SMA study of zolgensma.https:\/\/www.zolgensma.com\/clinical-studies\/presymptomatic-study-results. Accessed December 8 2020."},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31408-8"},{"key":"e_1_2_13_28_1","doi-asserted-by":"crossref","first-page":"1828","DOI":"10.1212\/WNL.94.15_supplement.1828","article-title":"Onasemnogene abeparvovec\u2010xioi gene\u2010replacement therapy for spinal muscular atrophy type 1 (SMA1): Phase 3 US Study (STR1VE) Update (1828)","volume":"94","author":"Shell R","year":"2020","journal-title":"Neurology."},{"key":"e_1_2_13_29_1","doi-asserted-by":"crossref","DOI":"10.1212\/WNL.92.15_supplement.S25.003","article-title":"FIREFISH Part 1: 1\u2010year results on motor function in babies with type 1 SMA (S25.003)","volume":"92","author":"Baranello G","year":"2019","journal-title":"Neurology"},{"key":"e_1_2_13_30_1","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1212\/WNL.94.15_supplement.1302","article-title":"FIREFISH Part 2: efficacy and safety of risdiplam (RG7916) in infants with type 1 spinal muscular atrophy (SMA) (1302)","volume":"94","author":"Servais L","year":"2020","journal-title":"Neurology."},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1710504"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-019-00656-w"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000007527"},{"key":"e_1_2_13_34_1","unstructured":"FinkelRS DayJW DarrasBT et al.One\u2010time intrathecal (IT) administration of AVXS\u2010101 IT gene therapy for spinal muscular atrophy: phase 1 study (STRONG). Abstract of the annual meeting of the Muscular Dystrophy Association August2020."},{"key":"e_1_2_13_35_1","doi-asserted-by":"crossref","DOI":"10.1212\/WNL.92.15_supplement.S25.007","article-title":"Update from SUNFISH part 1: safety, tolerability and PK\/PD from the dose\u2010finding study, including exploratory efficacy data in patients with type 2 or 3 spinal muscular atrophy (SMA) treated with risdiplam (RG7916) (S25.007)","volume":"92","author":"Mercuri E","year":"2019","journal-title":"Neurology"},{"key":"e_1_2_13_36_1","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1212\/WNL.94.15_supplement.1260","article-title":"SUNFISH Part 2: efficacy and safety of risdiplam (RG7916) in patients with type 2 or non\u2010ambulant type 3 spinal muscular atrophy (SMA) (1260)","volume":"94","author":"Mercuri E","year":"2020","journal-title":"Neurology."},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.26899"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000008207"}],"container-title":["Muscle &amp; Nerve"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mus.27358","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mus.27358","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mus.27358","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T15:50:01Z","timestamp":1725378601000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mus.27358"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,7]]},"references-count":37,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["10.1002\/mus.27358"],"URL":"https:\/\/doi.org\/10.1002\/mus.27358","archive":["Portico"],"relation":{},"ISSN":["0148-639X","1097-4598"],"issn-type":[{"value":"0148-639X","type":"print"},{"value":"1097-4598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,7]]},"assertion":[{"value":"2021-06-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}