Cathelicidin-related antimicrobial peptide (CRAMP) appears to be an essential muscle degeneration mediator in mouse models and could be a potential therapeutic target for patients with Duchenne muscular dystrophy (DMD) in the future, according to a recent study.
The authors aimed to assess the role of CRAMP in muscle degeneration by exposing mice to cardiotoxin barium chloride (BaCl2) via intramuscular injection in order to induce muscle degeneration and posterior regeneration.
In comparison with the control group, the BaCl2 group had a significant increase in CRAMP levels. Immunostaining showed a significant CRAMP accumulation in degenerating muscle. CRAMP levels returned to normal 8 days after exposure.
The study was published in the Journal of Cachexia, Sarcopenia and Muscle.
Read more about DMD therapies
Cathelicidin is an endogenous antimicrobial peptide involved in killing bacteria, bacterial lipopolysaccharide neutralization, and the activation of innate immune responses. The role of cathelicidins in sterile inflammation and tissue degeneration has been recently studied; however, its association with degenerative muscle diseases such as DMD remains unclear.
The majority of CRAMP was detected in neutrophils and, to a lesser extent, in macrophages. Injections of neutrophil-neutralizing antibodies decreased CRAMP levels in degenerated muscle. Researchers used biotinylated CRAMP to confirm that CRAMP infiltrates myocytes rather than being randomly diffused.
Furthermore, the authors also noted that 10 days after infiltration, CRAMP produced massive tissue necrosis. CRAMP was also administered to microtubules producing a decrease in microtubule integrity and cell proliferation.
The second part of the study involved using CRAMP-lacking mice to assess its true role in muscle degeneration. CRAMP-lacking mice did not appear to have any deficits in normal muscle development. After cardiotoxin administration, muscle with CRAMP showed necrotic fibers with inflammatory cells, while muscle without CRAMP did not exhibit any significant changes.
Although, after 12 days of cardiotoxin administration, both types of muscle had regenerated, CRAMP muscle showed a significant increase in interstitial space between new myofibers and similar higher-grade inflammation. After a month, CRAMP-lacking muscle had higher weight than CRAMP muscle.
“In this study, we provide genetic evidence for the role of CRAMP in promoting the progression of DMD,” the authors concluded.
Choi MC, Jo J, Lee M, Park J, Yao TP, Park Y. Cathelicidin‐related antimicrobial peptide mediates skeletal muscle degeneration caused by injury and Duchenne muscular dystrophy in mice. J Cachexia Sarcopenia. Published online September 4, 2022. doi:10.1002/jcsm.13065