{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:58:23Z","timestamp":1785437903800,"version":"3.56.0"},"reference-count":67,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Apulian Regional Council","award":["D.U.P. no. 246\/2019"],"award-info":[{"award-number":["D.U.P. no. 246\/2019"]}]},{"award":["D.U.P. no. 246\/2019"],"award-info":[{"award-number":["D.U.P. no. 246\/2019"]}],"id":[{"id":"https:\/\/ror.org\/05gd75v11","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background: Spinal Muscular Atrophy (SMA) is a neurodegenerative disease caused by reduced survival motor neuron (SMN) protein levels due to SMN1 gene mutations. The natural history of SMA has dramatically changed since innovative therapies were approved; among them, Risdiplam (an oral molecule) increases the peripheral levels of SMN by modifying the pre-mRNA slicing of the paralogous SMN2 that also codes for the protein. Methods: We performed longitudinal RNA sequencing on peripheral blood samples from 16 adult SMA patients (types II and III) before and after 12 months of Risdiplam treatment to assess transcriptomic changes. Results: During Risdiplam treatment, increased SMN2 transcript levels were observed, which was coherent with the clinical condition of the investigated SMA cohort. Upregulated mitochondria genes or pseudogenes (i.e., MT-ATP8 and MTND1P11) and downregulated autophagy-related pathways were also found. Baseline differences in gene expression between SMA type II and type III involved neurodegenerative (i.e., MS4A3, C4BPA, and NEILS3) and immune-related (B2M) genes. Conclusions: These findings support Risdiplam\u2019s systemic impact in adult SMA subjects and reveal molecular distinctions between SMA phenotypes (types II and III), which may be of some relevance for future clinical and therapeutic strategies.<\/jats:p>","DOI":"10.3390\/brainsci16060643","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T08:22:56Z","timestamp":1781684576000},"page":"643","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Longitudinal Transcriptomic Analysis Reveals Systemic Effects of Risdiplam in Adults with Spinal Muscular Atrophy"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4338-0392","authenticated-orcid":false,"given":"Maria","family":"Liguori","sequence":"first","affiliation":[{"name":"National Research Council, Department of Biomedicine, Institute of Biomedical Technologies, Bari Unit, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Consiglio","sequence":"additional","affiliation":[{"name":"National Research Council, Department of Biomedicine, Institute of Biomedical Technologies, Bari Unit, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3762-5800","authenticated-orcid":false,"given":"Eustachio","family":"D\u2019Errico","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Translational Biomedicine and Neuroscience, University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9546-6231","authenticated-orcid":false,"given":"Ylenia","family":"Antonacci","sequence":"additional","affiliation":[{"name":"National Research Council, Department of Biomedicine, Institute of Biomedical Technologies, Bari Unit, 70125 Bari, Italy"},{"name":"National Research Council, Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Coffa","sequence":"additional","affiliation":[{"name":"National Research Council, Department of Biomedicine, Institute of Biomedical Technologies, Bari Unit, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3141-6442","authenticated-orcid":false,"given":"Alessandro","family":"Introna","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Translational Biomedicine and Neuroscience, University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7429-3091","authenticated-orcid":false,"given":"Isabella Laura","family":"Simone","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/S1474-4422(12)70061-3","article-title":"Childhood Spinal Muscular Atrophy: Controversies and Challenges","volume":"11","author":"Mercuri","year":"2012","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0092-8674(95)90460-3","article-title":"Identification and Characterization of a Spinal Muscular Atrophy-Determining Gene","volume":"80","author":"Lefebvre","year":"1995","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"6307","DOI":"10.1073\/pnas.96.11.6307","article-title":"A Single Nucleotide in the SMN Gene Regulates Splicing and Is Responsible for Spinal Muscular Atrophy","volume":"96","author":"Lorson","year":"1999","journal-title":"Proc. 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