Congenital myopathies (CMYOs) have no curative treatment, and management is supportive standard of care (SoC). We evaluated whether 24 weeks of oral salbutamol added to SoC improves motor function and muscle strength versus SoC alone in children and adolescents with CMYO.

In this randomised, open-label, blinded-endpoint, crossover trial conducted in Sweden, eligible participants (aged 6.5–16.0 years) with genetically confirmed CMYO were stratified by ambulatory status and randomised (1:1) to oral salbutamol plus SoC or SoC only for 24 weeks, followed by crossover after a 4 week washout period. The primary outcome was change in Motor Function Measure-32 (MFM-32) total score during each treatment period. Efficacy analyses were performed in the intention-to-treat population, comprising all randomised participants. The trial was registered at ClinicalTrials.gov (NCT05099107).

Between October 25, 2021, and December 31, 2023, 18 participants (11 males and 7 females) met the eligibility criteria and were randomly assigned to study groups. The mean age at diagnosis was 2.1 years (range 0–6.5), and the mean age at the screening visit was 10.4 years (range 6.5–16.0). All but one participant had undergone muscle biopsy and all had a verified genetic diagnosis prior to study entry. The underlying genetic aetiologies were RYR1 (n = 7), ACTA1 (n = 4), NEB (n = 3), and SELENON, MYBPC1, TPM2, and TPM3 (each n = 1). Salbutamol improved MFM-32 total score versus SoC only (adjusted mean difference 3.61 points, 95% CI 1.74–5.48; P = 0.0009). No serious or unexpected serious adverse events occurred. Two adverse events occurred during salbutamol treatment (mammary gland swelling and dry eyes) and none during SoC only. Expected side effects included palpitations (n = 5) and tremor (n = 1).

The between-treatment difference in MFM-32 exceeded previously reported thresholds for meaningful change in congenital-onset neuromuscular disorders. These findings support oral salbutamol as a potential symptomatic treatment option for children and adolescents with CMYOs. Larger multicentre studies with longer follow-up are needed to confirm these findings and evaluate the durability of treatment effects.