Document Type

Article

Publication Date

5-21-2025

Keywords

Duchenne muscular dystrophy, canakinumab, interleukin 1 beta, myostatin, biomarkers

Abstract

Background: Duchenne muscular dystrophy (DMD) is a progressive muscular disease associated with muscle fiber degeneration and increased inflammatory responses including Interleukin-1 beta (IL-1β) and other cytokines. Canakinumab (Ilaris) is an anti-human IL-1β monoclonal antibody that neutralizes IL-1β. Methods: We completed an open-label, single dose pilot study of canakinumab 2 mg/kg subcutaneous injection in steroid naïve boys with DMD older than 2 years of age to determine safety and potential serum response biomarkers of efficacy at 4-weeks post treatment. Proteome profiling was performed using high throughput multiplexing aptamer SomaScan assay based technology targeting 1,500 unique serum proteins. Results: Three subjects completed the study with no adverse events reported and no significant changes in safety labs. Proteomic analysis within 4 weeks of treatment identified significantly decreased inflammation associated factors including plasma serine protease inhibitor, interleukin-6 receptor alpha, Lymphocyte antigen 86, Immunoglobulin D and myostatin. Significantly increased proteins included muscle-associated proteins aldolase A and lactate dehydrogenase B. Conclusions: Canakinumab 2 mg/kg dose is safe for children with DMD and demonstrated potential response biomarkers of efficacy in treating related muscle disease. Canakinumab did not affect the circulating levels of IL-1β but did decrease some key proinflammatory markers and myostatin. Increased muscle specific proteins could be associated with increased physical activities or damage seen in young patients with DMD. Further studies using canakinumab for a longer treatment period may demonstrate increased benefit.

Comments

https://doi-org.proxy.binghamton.edu/10.1177/22143602251319

Publisher Attribution

Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).

Creative Commons License

Creative Commons Attribution-NonCommercial 4.0 International License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License

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