MyomiR networks in spinal muscular atrophy

Barbo, Maruša (author), Koritnik, Blaž (author), Leonardis, Lea (author), Dolžan, Vita (author), Ravnik-Glavač, Metka (author)

Disease-modifying therapies have significantly influenced the clinical course of spinal muscular atrophy (SMA), yet objective biomarkers for monitoring disease progression and treatment remain limited. We profiled four muscle-specific miRNAs (myomiRs), ten bioinformatically predicted mRNA targets, two functionally associated lncRNAs, and SMN transcripts in whole blood from 50 adults with SMA types II-IV. Using RT-qPCR, we assessed associations between baseline RNA expression and demographic and clinical parameters, including SMA type, ambulatory status, motor and respiratory function, and explored longitudinal changes during nusinersen (24 months) and risdiplam (6/12 months) treatment. At baseline, miR-206 was higher in type III than in type II and in ambulatory compared to non-ambulatory patients, while it correlated positively with motor and respiratory function and with SMN mRNA variants (total, FL, and ∆7). SMN transcript levels were higher in patients with more SMN2 copies and in ambulatory patients and showed positive correlations with motor and respiratory function. miR-133a-3p and miR-133b correlated negatively with upper limb and respiratory function, and sex-related differences were observed for miR-133a-3p, FGFR1, ANXA2, and LINCMD1. During nusinersen treatment, we observed a decrease in miR-206, LINCMD1, and lnc-GJA1-2, alongside modest reductions in SMN-∆7 and total SMN. In contrast, risdiplam induced a peripheral splicing shift: SMN-FL and the FL/∆7 ratio increased, while SMN-∆7 decreased; miR-133a-3p also decreased at 6 months. By integrating muscle-derived RNAs, particularly miR-206, with blood SMN2 splicing changes, we propose a composite, blood-based biomarker approach for assessing SMA status and treatment-associated molecular changes and highlight myomiR-lncRNA-mRNA networks that suggest disease-relevant mechanisms.

• Language: English
• Keywords: SMN2 splicing, biomarkers, spinal muscular atrophy, IncRNA, miR-206, myomiR
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2026
• Number of pages: 19 str.
• Numbering: Vol. 63, iss. 1, art. 601
• PID: 20.500.12556/RUL-182564
• UDC: 616.8:577.2
• ISSN on article: 0893-7648
• DOI: 10.1007/s12035-026-05862-4
• COBISS.SI-ID: 277840387
• Publication date in RUL: 19.05.2026

Record is a part of a journal

• Title: Molecular neurobiology
• Shortened title: Mol. neurobiol.
• Publisher: Springer Nature
• ISSN: 0893-7648
• COBISS.SI-ID: 25975552

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Title: associations with clinical severity and treatment response
• Keywords: izrezovanje SMN2, biološki označevalci, spinalna mišična atrofija, miomiR

Projects

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: P1-0170
• Name: Molekulski mehanizmi uravnavanja celičnih procesov v povezavi z nekaterimi boleznimi pri človeku

• Funder: ARIS - Slovenian Research and Innovation Agency
• Funding programme: Young researchers