Key result
Adult centronuclear myopathies show stable but reduced neuromuscular function and altered biomarker levels.
Why the study?
Robust baseline data are essential to understand disease trajectories and enable trial readiness for rare neuromuscular disorders like XLMTM and ADCNM.
Observational (n=26)
Yes
This dataset provides valuable phenotypic, functional, and biomarker characterization of adult XLMTM and ADCNM, emphasizing the importance of baseline data for ultrarare disease trials.
Characterizes stable yet impaired function in adult XLMTM/ADCNM; hypothesis-generating for biomarker-driven trials in these ultrarare myopathies.
Background X-linked myotubular myopathy (XLMTM) and autosomal dominant centronuclear myopathy (ADCNM) are rare neuromuscular disorders characterized by severe weakness and respiratory impairment and have recently been the focus of therapeutic development. Robust baseline data are essential to understand disease trajectories and enable trial readiness. We present baseline clinical, functional, and biomarker findings from the terminated Unite-CNM trial (NCT04033159), a basket study of the antisense oligonucleotide DYN101, designed to modulate DNM2 expression in adolescents and adults with XLMTM or ADCNM. Methods Screening and baseline evaluations included medical history, patient-reported outcomes, quantitative muscle strength and motor function, respiratory testing, muscle ultrasound and histology, and biomarker analyses (DNM2 protein, creatinine, creatine kinase, cystatin C, myostatin, and microRNAs) in plasma and muscle. Results Twenty-six patients were screened (15 DNM2 , 11 MTM1 ); 14 entered the study. Patient-reported measures highlighted swallowing challenges and variable personal goals. Baseline respiratory impairment was variable in DNM2 and female MTM1 patients but consistently reduced in males with MTM1 (FVC% and FEV1% stable over follow-up to 78 weeks). MFM32 scores were similar across genotypes and sexes, while Myogrip strength was reduced versus age norms yet stable longitudinally. Muscle pathology was comparable across groups. Biomarker analyses showed altered DNM2 protein, reduced myostatin, and specific abnormalities in creatinine, creatine kinase, cystatin C, and microRNAs. Conclusion This dataset provides valuable phenotypic, functional, and biomarker characterization of adult XLMTM and ADCNM, emphasizes the importance of baseline data for ultrarare disease trials, and highlights the need for protocol flexibility in response to safety signals and disruptions (e.g. COVID-19).
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Prikhodko et al. (2026) conducted an observational in X-linked myotubular myopathy (XLMTM) and autosomal dominant centronuclear myopathy (ADCNM) (n=26). DNM2 or MTM1 mutations vs. Healthy controls (for biomarkers) was evaluated on Baseline clinical, functional, histopathological, and biomarker characteristics. Adults with XLMTM and ADCNM exhibited stable but reduced respiratory and motor function, moderate to severe centronuclear myopathy pathology, and altered DNM2 and myostatin biomarker levels.
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