Duchenne Muscular Dystrophy (DMD) is a rare X-linked recessive disease that predominantly affects boys due to mutations in the dystrophin gene, causing progressive muscle degeneration. Existing therapies provide only modest disease slowing and are associated with significant and dose-limiting adverse effects, such as those seen with corticosteroids and givinostat. Consequently, there remains a substantial unmet need for safe and effective small-molecule treatments for DMD patients, independent of mutation type.
RT001/PEPR124 has previously demonstrated significant improvements in muscle function and histopathological outcomes in a 1-month and 3-month D2.mdx mouse model of DMD (Poster no. LB435, MDA 2025). Building on these findings, the effect of RT001 was further evaluated in a panel of pro-inflammatory (IL-6, TNF-a, CD45), pro-fibrotic (Col1A1, Col3A1, TGFb-1) and regeneration / muscle damage (Myostatin, Emb-MyHC, CK) specific biomarkers relevant to muscular dystrophies (DMD, LGMD). RT001 modulated the expression of the relevant genes / proteins and showed promising outcomes on the biomarkers tested.
Given the novel poly-pharmacology of RT001 and its role in modulating fibro-adipogenic progenitor (FAP) cells, its effects were further assessed using a translationally relevant human 3D-engineered skeletal muscle model derived from DMD patient iPSCs, co-cultured with FAPs from healthy donors. In this system, RT001 mitigated acute fatigue, preserved excitation–contraction coupling, and increased resistance to tissue shortening, indicating enhanced mechanical stability. Collectively, these results suggest that RT001 could promote functional maturation and mechanical resilience in muscle tissues of DMD patients.
RT001 is expected to enter clinical development in 2026. The protocol for the planned Phase 2a study will be presented in the poster.