A pseudopeptide growth hormone secretagogue (JMV2894) reduced muscle wasting and improved muscle fiber size in a severe mouse model of Duchenne muscular dystrophy through IGF-1 signaling.
Increased muscle fiber size + decreased wasting genesJMV2894 increased myofiber size while reducing expression of Atrogin and MuRF1 (muscle atrophy genes) in a severe DMD mouse model
What the researchers found
JMV2894, a pseudopeptide growth hormone secretagogue, showed remarkable anti-atrophic effects in a severe mouse model of Duchenne muscular dystrophy (D2-mdx). At the lower dose (640 µg/kg), it significantly increased muscle fiber size and decreased expression of muscle-wasting genes (Atrogin and MuRF1).
The treatment partially improved hind limb muscle function, reduced muscle echo-density (a measure of tissue damage), and decreased expression of matrix-remodeling genes including MMP-9, ADAMTS-5, TGF-β1, and type I collagen. However, the anti-fibrotic effect was only mild histologically despite the gene expression changes.
The mechanism appears to be GH-mediated: JMV2894 increased IGF-1 gene expression and plasma levels, along with IGF-1 receptor and downstream signaling proteins. The treatment was well-tolerated at both doses over 6 weeks, though limited muscle drug exposure suggests improved formulations could enhance results.
Why it matters
Duchenne muscular dystrophy is a devastating genetic disease with no cure, causing progressive muscle wasting and early death. This study provides the first evidence that a growth hormone secretagogue peptide can combat muscle atrophy in a severe DMD mouse model through IGF-1 signaling. The anti-atrophic, anti-inflammatory, and anti-fibrotic properties of JMV2894 suggest growth hormone secretagogues could be a multi-target therapeutic approach for DMD.
The numbers in context
Doses: 640 and 1280 µg/kg SC · 6 weeks treatment · 4-week-old D2-mdx mice · Increased myofiber size · Decreased Atrogin + MuRF1 expression · Increased IGF-1 plasma levels · Decreased MMP-9, ADAMTS-5, TGF-β1, collagen Iα1
How the study worked
Four-week-old D2-mdx mice (a severe DMD model with hyper-fibrotic and atrophic phenotype) received subcutaneous JMV2894 at 640 or 1280 µg/kg for six weeks. Researchers measured hind limb muscle function (plantar flexor torque), muscle volume (ultrasound), echo-density, muscle fiber size (histology), fibrosis, gene expression of matrix-remodeling and atrophy markers, and IGF-1 levels in plasma and tissue.
Who was studied
D2-mdx mice (severe Duchenne muscular dystrophy model), treated from 4 weeks of age for 6 weeks
What this study cannot tell us
This is a preclinical mouse study — results may not translate to human DMD patients. The D2-mdx model, while severe, doesn't fully replicate human disease. The anti-fibrotic effect was mild despite gene expression changes, and limited drug exposure to muscle tissue suggests formulation improvements are needed. The lower dose was surprisingly more effective for some outcomes, which is not fully explained.
How to read the evidence
This is a preclinical animal study in a mouse model of DMD. While the experimental design is thorough and the results are promising, no human data exists for this compound in DMD, and the limited muscle drug exposure suggests optimization is still needed.
When this study was published
Published in 2025, this is cutting-edge research exploring a novel therapeutic approach for DMD. The D2-mdx mouse model used is considered more clinically relevant than the classic mdx model.
The bigger picture
DMD treatment has historically focused on corticosteroids and gene therapy approaches. Growth hormone secretagogues offer a completely different angle — combating muscle atrophy through the GH/IGF-1 axis while also reducing inflammation and fibrosis. If the formulation can be improved for better muscle exposure, GHS peptides could become a supportive therapy alongside emerging gene-based treatments for DMD.
Questions still open
- Could improved drug formulations (such as depot injections or nanoparticle delivery) increase muscle exposure and enhance the anti-fibrotic effects?
- Why was the lower dose more effective for some outcomes — is there an inverted dose-response relationship?
- Would combining JMV2894 with corticosteroids or gene therapy produce additive benefits in DMD?
Common questions
What is Duchenne muscular dystrophy and why is it so hard to treat?
How is a growth hormone secretagogue different from growth hormone itself?
Read the original research
Novel insights into the effects of JMV2894, a growth hormone secretagogue, in Duchenne muscular dystrophy: A preclinical study in the D2-mdx mouse model.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 193, 118767
Citation
Mantuano, Paola; Boccanegra, Brigida; Marinelli, Manuel; Cristiano, Enrica; Lenti, Roberta; Tulimiero, Lisamaura; De Bellis, Michela; Fehrentz, Jean-Alain; Denoyelle, Séverine; Bresciani, Elena; Torsello, Antonio; Mele, Antonietta; Liantonio, Antonella; Cappellari, Ornella; De Luca, Annamaria. (2025). Novel insights into the effects of JMV2894, a growth hormone secretagogue, in Duchenne muscular dystrophy: A preclinical study in the D2-mdx mouse model.. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 193, 118767. https://doi.org/10.1016/j.biopha.2025.118767