20.500.12556/DiRROS-29398 MyomiR networks in spinal muscular atrophy associations with clinical severity and treatment response 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. SMN2 splicing biomarkers spinal muscular atrophy IncRNA miR-206 myomiR izrezovanje SMN2 biološki označevalci spinalna mišična atrofija miomiR true false true Angleški jezik Slovenski jezik Neznano 2026-05-15 11:01:41 2026-05-15 11:01:42 2026-05-16 03:49:12 0000-00-00 00:00:00 2026 0 0 str. 1-19 no. 1, [Article no,] 601 Vol. 63 Apr. 2026 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.8:577.2 0893-7648 10.1007/s12035-026-05862-4 277840387 RAZ_Barbo_Marusa_2026.pdf RAZ_Barbo_Marusa_2026.pdf 1 E2A9216C4FB45FB1E17DDF4EE6B76C85 ab516891b929efb8cf34ca50dd2321be789f8b51e62a07d7b43b6ed191ab0229 cdc4859b-503c-11f1-8a5a-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=44060 https://link.springer.com/article/10.1007/s12035-026-05862-4 1 b3383244-503c-11f1-8a5a-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=44059 Univerzitetni klinični center Ljubljana 0 0 0