{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T11:13:58Z","timestamp":1777029238222,"version":"3.51.4"},"reference-count":139,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T00:00:00Z","timestamp":1618963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Spinal muscular atrophy (SMA) type 1 is a severe infantile autosomal-recessive neuromuscular disorder caused by a survival motor neuron 1 gene (SMN1) mutation and characterized by progressive muscle weakness. Without supportive care, SMA type 1 is rapidly fatal. The antisense oligonucleotide nusinersen has recently improved the natural course of this disease. Here, we investigated, with a functional proteomic approach, cerebrospinal fluid (CSF) protein profiles from SMA type 1 patients who underwent nusinersen administration to clarify the biochemical response to the treatment and to monitor disease progression based on therapy. Six months after starting treatment (12 mg\/5 mL \u00d7 four doses of loading regimen administered at days 0, 14, 28, and 63), we observed a generalized reversion trend of the CSF protein pattern from our patient cohort to that of control donors. Notably, a marked up-regulation of apolipoprotein A1 and apolipoprotein E and a consistent variation in transthyretin proteoform occurrence were detected. Since these multifunctional proteins are critically active in biomolecular processes aberrant in SMA, i.e., synaptogenesis and neurite growth, neuronal survival and plasticity, inflammation, and oxidative stress control, their nusinersen induced modulation may support SMN improved-expression effects. Hence, these lipoproteins and transthyretin could represent valuable biomarkers to assess patient responsiveness and disease progression.<\/jats:p>","DOI":"10.3390\/ijms22094329","type":"journal-article","created":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T12:47:07Z","timestamp":1619009227000},"page":"4329","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Nusinersen Modulates Proteomics Profiles of Cerebrospinal Fluid in Spinal Muscular Atrophy Type 1 Patients"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9219-1227","authenticated-orcid":false,"given":"Laura","family":"Bianchi","sequence":"first","affiliation":[{"name":"Functional Proteomics Laboratory, Department of Life Sciences, University of Siena, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Sframeli","sequence":"additional","affiliation":[{"name":"Nemo Sud Clinical Centre, 98125 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4078-7250","authenticated-orcid":false,"given":"Lorenza","family":"Vantaggiato","sequence":"additional","affiliation":[{"name":"Functional Proteomics Laboratory, Department of Life Sciences, University of Siena, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gian Luca","family":"Vita","sequence":"additional","affiliation":[{"name":"Nemo Sud Clinical Centre, 98125 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annamaria","family":"Ciranni","sequence":"additional","affiliation":[{"name":"Unit of Neurology and Neuromuscular Diseases, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Polito","sequence":"additional","affiliation":[{"name":"Unit of Neurology and Neuromuscular Diseases, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosaria","family":"Oteri","sequence":"additional","affiliation":[{"name":"Unit of Neurology and Neuromuscular Diseases, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eloisa","family":"Gitto","sequence":"additional","affiliation":[{"name":"Neonatal and Paediatric Intensive Care Unit, Department of Human Pathology in Adult and Developmental Age, University of Messina, 98125 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabrizio","family":"Di Giuseppe","sequence":"additional","affiliation":[{"name":"Dentistry and Biotechnology, and Proteomics Unit, Centre of Advanced Studies and Technoloy, Department Medical, Oral &amp; Biotechnological Sciences, \u201cG. d\u2019Annunzio\u201d, University of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Angelucci","sequence":"additional","affiliation":[{"name":"Dentistry and Biotechnology, and Proteomics Unit, Centre of Advanced Studies and Technoloy, Department Medical, Oral &amp; Biotechnological Sciences, \u201cG. d\u2019Annunzio\u201d, University of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Versaci","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, AOU Policlinico \u201cG. Martino\u201d, 98125 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7994-3391","authenticated-orcid":false,"given":"Sonia","family":"Messina","sequence":"additional","affiliation":[{"name":"Unit of Neurology and Neuromuscular Diseases, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Vita","sequence":"additional","affiliation":[{"name":"Nemo Sud Clinical Centre, 98125 Messina, Italy"},{"name":"Unit of Neurology and Neuromuscular Diseases, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8951-2106","authenticated-orcid":false,"given":"Luca","family":"Bini","sequence":"additional","affiliation":[{"name":"Functional Proteomics Laboratory, Department of Life Sciences, University of Siena, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0440-0354","authenticated-orcid":false,"given":"M\u2019hammed","family":"Aguennouz","sequence":"additional","affiliation":[{"name":"Unit of Neurology and Neuromuscular Diseases, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1038\/sj.ejhg.5201288","article-title":"New Insights on the Evolution of the SMN1 and SMN2 Region: Simulation and Meta-Analysis for Allele and Haplotype Frequency Calculations","volume":"12","author":"Ogino","year":"2004","journal-title":"Eur. 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