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Multicenter Study
. 2025 Jul;12(7):1368-1377.
doi: 10.1002/acn3.70070. Epub 2025 May 14.

Myostatin Levels in SMA Following Disease-Modifying Treatments: A Multi-Center Study

Fiorella Piemonte  1 , Sara Petrillo  1 , Anna Capasso  2   3 , Giorgia Coratti  2   3 , Adele D'Amico  1 , Michela Catteruccia  1 , Maria Carmela Pera  2   3   4 , Concetta Palermo  2   3 , Marika Pane  2   3 , Emanuela Abiusi  5 , Gianpaolo Cicala  2 , Marianna Villa  2 , Chiara Bravetti  2   3 , Chiara Arpaia  2   3 , Agnese Novelli  5 , Salvatore Falqui  5 , Stefania Fiori  5 , Giulia Napoli  6 , Silvia Baroni  6   7 , Francesco Danilo Tiziano  5   8 , Enrico Bertini  1 , Giacomo Comi  9   10 , Stefania Corti  9   10 , Eugenio Mercuri  2   3
Affiliations
Multicenter Study

Myostatin Levels in SMA Following Disease-Modifying Treatments: A Multi-Center Study

Fiorella Piemonte et al. Ann Clin Transl Neurol. 2025 Jul.

Abstract

Objective: This study investigated myostatin levels in SMA patients receiving disease-modifying therapies (DMTs) to understand their relationship with treatment duration and functional status.

Methods: Our study includes both cross-sectional and longitudinal analyses of myostatin levels in treated SMA patients. The longitudinal cohort included 46 treatment-naive patients assessed at baseline and 12 months post-treatment. Myostatin levels were measured using ELISA. Age-matched controls (n = 89) were included for comparison. The cross-sectional study included 128 patients with variable durations of treatment (from 0.4 to 7.2 years). In both cohorts, myostatin levels were correlated with SMA type, functional status, and clinical outcomes.

Results: Baseline myostatin levels were significantly lower than controls (p < 0.001), except during the neonatal period in presymptomatic patients. After 12 months of treatment, there were no significant changes compared to baseline levels (p = 0.1652). The only substantial changes were observed in presymptomatic neonates, who showed a reduction of myostatin despite treatment intervention. There was a significant correlation between myostatin levels, functional status, and SMA type both in the cross-sectional and longitudinal groups.

Interpretation: This study demonstrates lower myostatin levels in SMA patients compared to controls. The association between myostatin levels, functional status, and SMA type suggests its possible role as a disease severity biomarker. The utility of myostatin as a biomarker for DMT response remains controversial; while we observed no significant increase in myostatin levels following treatment, we also did not observe the progressive reduction previously reported in untreated patients.

Keywords: biomarkers; disease‐modifying therapies; myostatin; neuromuscular disorders; spinal muscular atrophy; treatment response.

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Conflict of interest statement

Giorgia Coratti reports are part of advisory boards from Biogen S.R.L., Roche, and Novartis outside the submitted work. Maria Carmela Pera is part of advisory boards for Roche outside the submitted work. Marika Pane is part of advisory boards for Biogen S.R.L. outside the submitted work. Enrico Bertini is part of advisory boards for Biogen S.R.L., Roche, PTC, UCB, and Pfizer outside the submitted work. Giacomo Comi is part of advisory boards from Biogen S.R.L., Roche, Scholar Rock, Sarepta, and Novartis outside the submitted work. Stefania Corti is part of advisory boards from Biogen S.R.L., Roche, Scholar Rock, and Novartis outside the submitted work. Eugenio Mercuri is part of advisory boards for Biogen S.R.L., Roche, and Novartis, Scholar Rock, Epirium, and Cytokinetics outside the submitted work. The other authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Myostatin levels by SMA type. (Panel A) baseline myostatin levels, (Panel B) 12‐month myostatin levels, (Panel C) changes in myostatin levels at 12 months, (Panel D), individual myostatin trajectories, (Panel E) changes in HFMSE scores, (Panel F) changes in CHOP INTEND scores.
FIGURE 2
FIGURE 2
Myostatin levels in relation to functional status.
FIGURE 3
FIGURE 3
Myostatin levels in relation to SMA type and functional status. (Panel A) overall, (Panel B) SMA I, (Panel C) SMA II, (Panel D) SMA III.
FIGURE 4
FIGURE 4
Myostatin levels in relation to SMA type, functional status and duration of treatment. (Panel A) presymptomatic patients, (Panel B) SMA I individuals, (Panel C) SMA II individuals, (Panel D) SMA III individuals.
See this image and copyright information in PMC

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