Related Experiment Video
Updated: Aug 8, 2025
Measurements of Motor Function and Other Clinical Outcome Parameters in Ambulant Children with Duchenne Muscular Dystrophy
Published on: January 12, 2019
Longitudinal Assessment of Creatine Kinase, Creatine/Creatinineratio, and Myostatin as Monitoring Biomarkers in
Nienke M van de Velde1, Zaïda Koeks1, Mirko Signorelli1
1From the Departments of Neurology (N.M.V., Z.K., J.V., E.H.N.), Biomedical Data Sciences (M.S.), Human Genetics (N.V., M.O., P.S.), and Clinical Chemistry and Laboratory Medicine (J.A.B.), Leiden University Medical Center, the Netherlands; Duchenne Center Netherlands (N.M.V., J.V., P.S., E.H.N.); European Reference Network for Rare Neuromuscular Diseases [ERN EURO-NMD] (N.M.V., Z.K., N.V., M.O., J.V., P.S., E.H.N.); Mathematical Institute (M.S.), Leiden University, the Netherlands; Analysis Group Inc (G.S., J.S.), Boston, MA; Solid Biosciences Inc (V.R., K.B.), Cambridge, MA; and NIHR Great Ormond Street Hospital Biomedical Research Centre (V.R.), Great Ormond Street Institute of Child Health, University College London, & Great Ormond Street Hospital Trust, United Kingdom.
Background And Objectives:
The slow and variable disease progression of Becker muscular dystrophy (BMD) urges the development of biomarkers to facilitate clinical trials. We explored changes in 3 muscle-enriched biomarkers in serum of patients with BMD over 4-year time and studied associations with disease severity, disease progression, and dystrophin levels in BMD.
Methods:
We quantitatively measured creatine kinase (CK) using the International Federation of Clinical Chemistry reference method, creatine/creatinineratio (Cr/Crn) using liquid chromatography-tandem mass spectrometry, and myostatin with ELISA in serum and assessed functional performance using the North Star Ambulatory Assessment (NSAA), 10-meter run velocity (TMRv), 6-Minute Walking Test (6MWT), and forced vital capacity in a 4-year prospective natural history study. Dystrophin levels were quantified in the tibialis anterior muscle using capillary Western immunoassay. The correlation between biomarkers, age, functional performance, mean annual change, and prediction of concurrent functional performance was analyzed using linear mixed models.
Results:
Thirty-four patients with 106 visits were included. Eight patients were nonambulant at baseline. Cr/Crn and myostatin were highly patient specific (intraclass correlation coefficient for both = 0.960). Cr/Crn was strongly negatively correlated, whereas myostatin was strongly positively correlated with the NSAA, TMRv, and 6MWT (Cr/Crn rho = -0.869 to -0.801 and myostatin rho = 0.792 to 0.842, all p < 0.001). CK showed a negative association with age (p = 0.0002) but was not associated with patients' performance. Cr/Crn and myostatin correlated moderately with the average annual change of the 6MWT (rho = -0.532 and 0.555, p = 0.02). Dystrophin levels did not correlate with the selected biomarkers nor with performance. Cr/Crn, myostatin, and age could explain up to 75% of the variance of concurrent functional performance of the NSAA, TMRv, and 6MWT.
Discussion:
Both Cr/Crn and myostatin could potentially serve as monitoring biomarkers in BMD, as higher Cr/Crn and lower myostatin were associated with lower motor performance and predictive of concurrent functional performance when combined with age. Future studies are needed to more precisely determine the context of use of these biomarkers.
