A recent study published in eClinicalMedicine has shed light on the potential of erythromycin in the treatment of myotonic dystrophy type 1 (DM1). DM1 is a debilitating condition caused by a CTG repeat expansion in the DMPK gene, leading to toxic RNA expression and dysregulated splicing. In a preclinical study, it was found that erythromycin could mitigate the toxicity of abnormal RNA and improve splicing and motor function in DM1 model mice.
To translate these promising preclinical findings into practical applications for DM1 patients, a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial was conducted at three centres in Japan. The trial, which took place between Nov 29, 2019, and Jan 20, 2022, enrolled 30 adult patients with DM1 who were randomly assigned to receive either placebo or erythromycin at two different daily doses (500 mg or 800 mg) for 24 weeks.
The primary outcome of the trial was to evaluate the safety and tolerability of erythromycin, while secondary measures included splicing biomarkers, 6-minute walk test results, muscle strength, and serum creatinine kinase (CK) values. The findings revealed that treatment-related gastrointestinal symptoms were more common in the erythromycin group, but all adverse events were mild to moderate and resolved spontaneously. No serious safety concerns were identified.
Furthermore, the study observed a decrease in CK levels from baseline to week 24 in the overall erythromycin group compared to the placebo group. Although this difference was not statistically significant (p = 0.070), there were statistically significant improvements in splicing biomarkers MBNL1 (p = 0.048) and CACNA1S (p = 0.042) in the erythromycin treated groups compared to placebo.
The researchers concluded that erythromycin demonstrated favorable safety and tolerability profiles in patients with DM1. They emphasized the need for a well-powered phase 3 trial to further evaluate its efficacy, building on the preliminary findings from this study.
This study was funded by the Japan Agency for Medical Research and Development and holds promise for the future treatment of DM1, offering hope to individuals affected by this challenging condition.
