This study aimed to research the role of creatine/creatinine ratio, myostatin, and creatine kinase in predicting the severity and progression of BMD. 

In Becker muscular dystrophy (BMD), the muscles become weaker because of reduced dystrophin levels with abnormal molecular weight. Since BMD is unusually rare, recruiting patients has been a challenge.

Moreover, slow disease progression and high functional variability make it challenging to capture possible drug efficacy during a clinical trial. Therefore, objective biomarkers are needed for trial design and conduct.

The replacement of muscle tissue with fat is a prominent sign of pathology in a muscle-wasting condition such as BMD, which makes markers related to muscle structure or integrity of particular interest. 

In muscular dystrophies, creatine kinase (CK) is commonly used as a diagnostic biomarker. However, its serum levels may not be optimal for monitoring the disease because they change as a result of both membrane pathology and muscle mass remaining, as well as other factors such as seasonal variation and physical activity.

Methodology

The researchers quantified creatine kinase (CK) using the IFCC reference method, creatine/creatinine ratio (Cr/Crn) using liquid chromatography-tandemometry (LCMS/MS), and myostatin with ELISA in serum. In addition, as part of a prospective natural history study lasting four years, functional performance was assessed using North Star Ambulatory Assessment (NSAA), ten-meter run velocity (TMRv), six-minute walking test (6MWT), and Forced Vital Capacity (FVC). 

Capillary Western immunoassay was used to quantify dystrophin levels in the anterior tibialis muscle, and linear mixed models were used to analyze correlations between biomarkers, age, functional performance, mean annual change, and prediction of concurrent operational performance. 

Results of The Study 

A total of 34 patients with 106 visits were included in the study. Eight patients were not ambulatory at baseline, and Cr/Crn and myostatin were highly patient-specific (intraclass correlation coefficient for both =0.960). 

A strong negative correlation was found between Cr/Crn and NSAA, TMRv, and 6MWT, while myostatin was strongly positively correlated with these variables. CK showed a negative association with age but was not associated with patients’ performance.

Myostatin and Cr/Crn levels correlated moderately with the 6MWT average annual change. Dystrophin levels were not correlated with the selected biomarkers or with performance. In the NSAA, TMRv, and 6MWT, up to 75% of the variance can be explained by Cr/Crn, myostatin, and age. 

Cr/Crn levels and myostatin levels could be used to monitor BMD since higher Cr/Crn levels and lower myostatin levels were linked with lower motor performance and predicted concurrent functional performance when combined with age. However, it will be necessary to conduct further studies to determine how these biomarkers are used in specific contexts.

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