{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:42:33Z","timestamp":1790516553446,"version":"4.1.0"},"reference-count":121,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,5,7]],"date-time":"2020-05-07T00:00:00Z","timestamp":1588809600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST107-2314-B-037-066 & MOST108-2314-B-037-073"],"award-info":[{"award-number":["MOST107-2314-B-037-066 & MOST108-2314-B-037-073"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011645","name":"Kaohsiung Medical University Chung-Ho Memorial Hospital","doi-asserted-by":"publisher","award":["KMUH-108-8R47"],"award-info":[{"award-number":["KMUH-108-8R47"]}],"id":[{"id":"10.13039\/501100011645","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Spinal muscular atrophy (SMA) is a congenital neuromuscular disorder characterized by motor neuron loss, resulting in progressive weakness. SMA is notable in the health care community because it accounts for the most common cause of infant death resulting from a genetic defect. SMA is caused by low levels of the survival motor neuron protein (SMN) resulting from SMN1 gene mutations or deletions. However, patients always harbor various copies of SMN2, an almost identical but functionally deficient copy of the gene. A genotype\u2013phenotype correlation suggests that SMN2 is a potent disease modifier for SMA, which also represents the primary target for potential therapies. Increasing comprehension of SMA pathophysiology, including the characterization of SMN1 and SMN2 genes and SMN protein functions, has led to the development of multiple therapeutic approaches. Until the end of 2016, no cure was available for SMA, and management consisted of supportive measures. Two breakthrough SMN-targeted treatments, either using antisense oligonucleotides (ASOs) or virus-mediated gene therapy, have recently been approved. These two novel therapeutics have a common objective: to increase the production of SMN protein in MNs and thereby improve motor function and survival. However, neither therapy currently provides a complete cure. Treating patients with SMA brings new responsibilities and unique dilemmas. As SMA is such a devastating disease, it is reasonable to assume that a unique therapeutic solution may not be sufficient. Current approaches under clinical investigation differ in administration routes, frequency of dosing, intrathecal versus systemic delivery, and mechanisms of action. Besides, emerging clinical trials evaluating the efficacy of either SMN-dependent or SMN-independent approaches are ongoing. This review aims to address the different knowledge gaps between genotype, phenotypes, and potential therapeutics.<\/jats:p>","DOI":"10.3390\/ijms21093297","type":"journal-article","created":{"date-parts":[[2020,5,7]],"date-time":"2020-05-07T03:10:38Z","timestamp":1588821038000},"page":"3297","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":121,"title":["New and Developing Therapies in Spinal Muscular Atrophy: From Genotype to Phenotype to Treatment and Where Do We Stand?"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7713-3627","authenticated-orcid":false,"given":"Tai-Heng","family":"Chen","sequence":"first","affiliation":[{"name":"Section of Neurobiology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA"},{"name":"Division of Pediatric Emergency, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Ph.D. Program in Translational Medicine, Graduate Institute of Clinical Medicine, Kaohsiung Medical University and Academia Sinica, Taipei 11529, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.pcl.2015.03.010","article-title":"Spinal muscular atrophies","volume":"62","author":"Darras","year":"2015","journal-title":"Pediatr. 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