Creatine/creatinineratio (Cr/Crn) and myostatin may be viable biomarkers for monitoring functional outcomes among patients with Becker muscular dystrophy (BMD), according to study findings published in Neurology.
Patients with BMD have dystrophin with an abnormal molecular weight which leads to progressive muscle weakness. It has been difficult to conduct a clinical trial for BMD in part due to its rarity (1 in 18,000 live male births) but also due to its functional variability and slow disease progression. The researchers asserted that identifying objective biomarkers may enrich the clinical trial process by enabling more precise patient selection, thereby allowing trials to proceed with smaller sample sizes.
To evaluate for potential biomarkers, adults (N=34) with BMD were recruited from the Dutch Dystrophinopathy Database. Changes in biomarkers were assessed in blood samples collected between 2014 and 2019 and correlated with the change in functional status and disease progression.
The patients were mean age, 42.2 (standard deviation [SD], 13.0) years, they had a body mass index (BMI) of 25.3 (SD, 4.3) kg/m2, 76.5% were ambulatory, and the most common genetic mutation was a deletion at 45-47 (29.4%).
At baseline, the patients had a median North Star Ambulatory Assessment (NSAA) score of 28.0 (range, 5.0-34.0) points, ten-meter run/walk (TMRv) of 1.0 (range, 0.0-4.2) m/s, 6 minute walk test (6MWT) of 329.5 (range, 0-650.0) m, forced vital capacity percent predicted (FVC) of 91.0% (range, 19.0%-118.0%), and dystrophin percentage of 38.9% (range, 18.6%-86.4%).
Interclass correlation coefficients of both Cr/Crn and myostatin were high, indicating they were patient-specific and heterogenous across the cohort whereas creatine kinase (CK) was found to be correlated with age.
Among ambulatory patients, Cr/Crn was negatively correlated with NSAA (ρ, -0.84), TMRv (ρ, -0.87), 6MWT (ρ, -0.53), and FVC (ρ, -0.45) and myostatin was positively correlated with NSAA (ρ, 0.84), TMRv (ρ, 0.79), 6MWT (ρ, 0.56), and FVC (ρ, 0.58). For nonambulatory patients, Cr/Crn (ρ, 0.83) and myostatin (ρ, 0.85) were also correlated with NSAA.
The yearly change in 6MWT was associated with both Cr/Crn (ρ, 0.83; P <.001) and myostatin (ρ, 0.83; P <.001). No other correlations were observed between yearly change in functional status with biomarkers.
Using these biomarkers and prognostic characteristics, concurrent performance, according to NSAA, TMRv, and 6MWT was explained best by age, Cr/Crn, and myosin, explaining 75% of the total variance.
The findings of this study may be limited, as the timing of blood draws varied from patient to patient.
“[C]reatine/creatinineratio and myostatin may be used as monitoring biomarkers in BMD … they improved prediction of concurrent functional performance when combined with age,” the researchers stated. They added, “Future studies are needed to more precisely determine the context of use of these biomarkers.”
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
van de Velde NM, Koeks Z, Signorelli M, et al. Longitudinal assessment of creatine kinase, creatine/creatinineratio and myostatin as monitoring biomarkers in Becker muscular dystrophy. Neurology. Published online December 5, 2022. doi:10.1212/WNL.0000000000201609