Researchers from the United States and Canada developed a new model that could explain the variability in the rate of disease progression and response to treatment in patients with Duchenne muscular dystrophy (DMD). The new model could help define better inclusion criteria in clinical trials, stratify patients for subgroup analysis, and monitor disease progression in individual patients.
For the development of the model, the team led by Utkarsh J. Dang, PhD, from the Department of Health Sciences at Carleton University in Ottawa, Canada, analyzed boys with DMD, 4 to 10 years of age, who were either untreated or treated with steroidal anti-inflammatory drugs (n=209) or treated with vamorolone (n=46).
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The study is published in the Journal of Neuromuscular Diseases.
The researchers used the results of 3 timed function tests to develop their model. These included the supine-to-stand test, the 10-meter walk/run test, and the 4-stair climb test.
They identified 3 classes of differentially progressing early-age motor trajectories.
They reported that a lower speed at baseline in performing the timed function tests, the loss of the ability to finish a timed function test at an earlier age, and lower predicted speeds in performing the timed function tests were associated with faster disease progression.
They also reported that earlier steroid treatment was associated with greater speed on the timed function tests.
The moderate progression class had the biggest difference in performance between patients who received steroid treatment early and those who were not treated.
When they calculated sample sizes using the class that had the largest treatment response, the researchers saw a large reduction in the required sample size compared to when summaries from all participants were used.
Finally, the researchers found that when the mutation in the DMD gene was closer to the beginning of the gene, the disease tended to progress more slowly.
“Our findings show class-related trajectories of motor outcomes and pharmacological response to corticosteroids, and suggest that enrichment strategies and/or subgroup analyses could be considered further in design of therapeutic interventions in DMD,” the authors concluded.
Fang Y, McDonald CM, Clemens PR, et al; CINRG DNHS and Vamorolone 002/003/LTE Investigators. Modeling early heterogeneous rates of progression in boys with Duchenne muscular dystrophy. J Neuromuscul Dis. Published online February 14, 2023. doi:10.3233/JND-221527