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Nusinersen, an antisense oligonucleotide, was approved for SMA treatment to compensate the deficit of the encoded protein SMN by modulating the pre\u2013mRNA splicing of <jats:italic>SMN2<\/jats:italic>, the centromeric homologous of <jats:italic>SMN1<\/jats:italic>, thus inducing the production of a greater amount of biologically active protein. Here, we reported a 10-month transcriptomics investigation in 10 adult SMA who received nusinersen to search for early genetic markers for clinical monitoring. By comparing their profiles with age-matched healthy controls (HC), we also analyzed the changes in miRNA\/mRNAs expression and miRNA-target gene interactions possibly associated with SMA. A multidisciplinary approach of HT-NGS followed by bioinformatics\/biostatistics analysis was applied. Within the study interval, those SMA patients who showed some clinical improvements were characterized by having the <jats:italic>SMN2\/SMN1<\/jats:italic> ratio slightly increased over the time, while in the stable ones the ratio decreased, suggesting that the estimation of <jats:italic>SMN2\/SMN1<\/jats:italic> expression may be an early indicator of nusinersen efficacy<jats:bold>.<\/jats:bold> On the other hand, the expression of 38\/147 genes\/genetic regions DE at T0 between SMA and HC like <jats:italic>TRADD<\/jats:italic> and <jats:italic>JUND<\/jats:italic> resulted \u201crestored\u201d at T10. We also confirmed the dysregulation of miR-146a(-5p), miR-324-5p and miR-423-5p in SMA subjects. Of interest, miR-146a-5p targeted <jats:italic>SMN1<\/jats:italic>, in line with experimental evidence showing the key role of astrocyte-produced miR-146a in SMA motor neuron loss. Molecular pathways such as NOTCH, NF-kappa B, and Toll-like receptor signalings seem to be involved in the SMA pathogenesis. <\/jats:p>","DOI":"10.1007\/s12031-024-02251-1","type":"journal-article","created":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T15:42:32Z","timestamp":1727365352000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["An early Transcriptomic Investigation in Adult Patients with Spinal Muscular Atrophy Under Treatment with Nusinersen"],"prefix":"10.1007","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4338-0392","authenticated-orcid":false,"given":"Maria","family":"Liguori","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Bianco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Introna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Consiglio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giammarco","family":"Milella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Abbatangelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eustachio","family":"D\u2019Errico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavio","family":"Licciulli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Grillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella Laura","family":"Simone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,26]]},"reference":[{"key":"2251_CR1","doi-asserted-by":"publisher","unstructured":"Abiusi E, Infante P, Cagnoli C, Lospinoso Severini L, Pane M, Coratti G, Pera MC, D\u2019Amico A, Diano F, Novelli A et al (2021) SMA-miRs (miR-181a-5p, -324-5p, and -451a) are overexpressed in spinal muscular atrophy skeletal muscle and serum samples. eLife 10:e68054. https:\/\/doi.org\/10.7554\/eLife.68054","DOI":"10.7554\/eLife.68054"},{"key":"2251_CR2","doi-asserted-by":"publisher","first-page":"916","DOI":"10.3390\/biology12070916","volume":"12","author":"C Agliardi","year":"2023","unstructured":"Agliardi C, Guerini FR, Bolognesi E et al (2023) VDR gene single nucleotide polymorphisms and autoimmunity: a narrative review. 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