Congenital myopathies are a heterogeneous family of disorders that typically announce themselves in early childhood with floppiness and generalised muscle weakness, most prominently in the muscles closest to the trunk. Severity spans an enormous range: the most affected infants are born with respiratory insufficiency and swallowing difficulties, while milder cases may only become apparent in adolescence or adulthood. Birth prevalence has been estimated at roughly 15 per 100,000 live births, and more than 40 different genes have been implicated, although about one in five patients still lack a confirmed genetic diagnosis. Despite this genetic diversity, the underlying cellular defects converge on a handful of mechanisms, including disturbed calcium handling in muscle fibres, abnormal sarcomeric proteins, and defects in membrane trafficking and cytoskeletal organisation.

It is precisely this convergence that made salbutamol an attractive candidate. As a β2-adrenergic agonist, the drug exerts anabolic effects on skeletal muscle, increasing protein synthesis, reducing protein degradation, and shifting myosin heavy chain expression from slow type I fibres towards fast type IIa fibres. Many congenital myopathies share type 1 fibre predominance and muscle fibre atrophy, so a drug that counteracts these features could plausibly help patients regardless of which faulty gene they carry. Earlier open-label studies in Duchenne muscular dystrophy and facioscapulohumeral muscular dystrophy hinted at short-term gains, but placebo-controlled trials failed to show sustained benefit, and a small pilot in core myopathies was too limited in design to be conclusive.

The new trial, known as COMPIS, was designed to settle the question with far greater rigour. Led by researchers at Queen Silvia’s Children’s Hospital in Gothenburg, with nationwide recruitment through paediatric neuromuscular centres in Stockholm, Lund/Malmö and Uppsala, the study enrolled 18 participants aged 6 to 30 with genetically verified congenital myopathies. Crucially, the cohort included both children who could walk and those who could not, and baseline functional severity ranged from severely impaired to mildly affected. Genetic causes included variants in RYR1, ACTA1, NEB, SELENON, TPM2, TPM3 and MYBPC1, reflecting the true diversity of clinical practice rather than a narrowly selected subgroup.

The crossover design meant every participant served as their own control. After a screening visit, participants were randomised to receive either 24 weeks of daily oral salbutamol added to standard of care, or standard of care alone, followed by a four-week washout and then the alternate treatment. Because participants and treating physicians inevitably knew which treatment was being given, the investigators masked the physiotherapists and occupational therapists who performed all functional assessments, ensuring that outcome measurement remained objective. The primary endpoint was the Motor Function Measure-32, a validated 32-task assessment of gross and fine motor function scored out of 96 points.

The results were unambiguous. During salbutamol treatment, the mean MFM-32 total score rose by 3.72 points, compared with an essentially flat 0.11 points during standard care alone, yielding an adjusted mean difference of 3.61 points in favour of the drug. That margin exceeds previously established thresholds for clinically meaningful change in congenital-onset neuromuscular disorders. Improvements were concentrated in the domains most affected by the disease, namely standing and transfers, and axial and proximal motor function. Dominant hand grip strength also increased significantly, and muscle strength measured by hand-held myometry trended upwards across all tested muscle groups.

Perhaps most striking were the gains in respiratory and ambulatory function. Seated forced vital capacity, a key indicator of breathing capacity, increased by 0.20 litres relative to control, a difference the authors consider particularly important because respiratory insufficiency is a common and morbid manifestation of congenital myopathies even when limb function appears stable. Among the 11 ambulatory participants, six-minute walking distance improved by an estimated 38 metres, and the time needed to rise from lying on the floor fell by 1.6 seconds, corresponding on log-scale analysis to a 9 percent increase in walking distance and a 23 percent reduction in rise time. For families, such gains translate into greater independence and delayed reliance on assistive devices and home adaptations.

Safety and tolerability were reassuring. Only two adverse events occurred during salbutamol treatment, neither clearly related to the drug, and there were no serious adverse events. Six participants experienced mild, expected pharmacological side effects, chiefly transient palpitations and one case of tremor, which resolved within one to two weeks in nearly all cases. No arrhythmias or clinically relevant electrocardiographic abnormalities emerged, blood pressure and heart rate stayed within normal ranges, and no participant discontinued treatment. Notably, every single participant chose to continue taking salbutamol after the study ended. Five participants gained a clinically significant amount of weight during treatment, reporting increased appetite, but statistical adjustment for weight change did not alter the findings.

The authors are careful to acknowledge limitations. The sample of 18 participants, while a triumph of recruitment in such a rare disease, was too small to detect differences in response by genotype, age or sex, and the open-label nature means patient-reported outcomes could be influenced by expectation. Longer-term studies will be needed to determine whether the benefits persist. Nevertheless, the trial stands as the first randomised, controlled, blinded-endpoint study of salbutamol in this population, and its implications reach beyond congenital myopathies. At a time when gene therapies for these disorders have stumbled, one trial was halted after treatment-related deaths, salbutamol offers a low-cost, globally marketed alternative that could be deployed now under multidisciplinary neuromuscular care, with baseline cardiac evaluation and monitoring. The researchers also emphasise a broader lesson: as repurposed medicines enter clinical practice, preserving the affordability and worldwide availability of generic drugs will be essential to ensuring equitable access for the patients who need them.

Subject of Research: A randomised crossover trial of oral salbutamol for motor function and muscle strength in congenital myopathies

Article Title: Effects of oral salbutamol treatment on motor function and muscle strength in congenital myopathies (COMPIS): a single-centre, randomised, open-label, blinded-endpoint, crossover trial in Sweden

Article References: Michael, E., Staaf, P., Gudmundsson, M., Klanac, B., Weichbrodt, J., Edofsson, U., Thuestad, I. J., Sejersen, T., Imberg, H., & Darin, N. (2026). Effects of oral salbutamol treatment on motor function and muscle strength in congenital myopathies (COMPIS): a single-centre, randomised, open-label, blinded-endpoint, crossover trial in Sweden. eClinicalMedicine, Article 104186. https://doi.org/10.1016/j.eclinm.2026.104186

Image Credits: AI Generated

DOI: 10.1016/j.eclinm.2026.104186

Keywords: congenital myopathies, salbutamol, drug repurposing, neuromuscular disorders, randomised crossover trial, muscle strength, motor function, respiratory function, RYR1, pediatric neurology, eClinicalMedicine, rare disease