Hiroshima – October 3, 2026 -- Ractigen Therapeutics presented first-in-human data showing its systemically delivered small activating RNA (saRNA), RAG-18, produced 3.5- to 5.3-fold increases in sarcolemmal utrophin expression in boys with Duchenne muscular dystrophy (DMD), marking the first clinical proof-of-mechanism for RNA activation (RNAa) in a monogenic disease. The data were disclosed in a Late-Breaking Oral Presentation at the 31st Annual Congress of the World Muscle Society (WMS 2026) in Hiroshima, Japan.
Paired biopsies confirm target engagement without serious safety signals
In Cohort 1 (15 mg monthly IV, n=3), paired contralateral muscle biopsies at Day 113 showed a 3.5- to 5.3-fold upregulation of sarcolemmal utrophin in mature myofibers and a 4.1- to 4.7-fold increase in regenerating myofibers, confirmed via quantitative immunofluorescence with laminin co-staining. The trial recorded zero dose-limiting toxicities, zero serious adverse events, and no Grade 3 or higher treatment-emergent adverse events through Day 169. All adverse events were mild, transient, and resolved without intervention; no dose interruptions or discontinuations occurred.
Tissue remodeling and reduced inflammation accompany target engagement
Morphometric analysis at Day 113 showed mean myofiber cross-sectional area increased 5% to 15%, with fiber diameter gains of 5.34 to 27.50 μm, absent drug-induced myonecrosis or inflammation. Muscle fat fraction dropped 3% to 10%. Quantitative MRI revealed thigh muscle T2 relaxation time reductions of up to 11.6% by Day 169, indicating resolution of active muscle edema.
Functional trajectories vary but trend positive across pulmonary measures
All three participants showed positive spirometric trends over 24 weeks: forced vital capacity (FVC%) rose by 2.8% to 41.0%, and forced expiratory volume (FEV1%) increased 2.8% to 34.0%. Ambulatory results were mixed — one early-ambulatory 6.8-year-old gained 36.5 meters on the six-minute walk distance (6MWD) test, while a 12.7-year-old late-ambulatory participant held steady (−1.0 m) with improved 4-stair climb time. A third participant, age 7.3, declined by 62.5 meters. NSAA scores fell uniformly by 3 points across all participants. Left ventricular ejection fraction stayed above 55% in all three boys throughout follow-up.
Three distinct mutation types responded in the same direction
Professor Yi Dai of Peking Union Medical College Hospital, the trial's Principal Investigator, noted the three treated boys carried three different DMD mutation types yet showed consistent upregulation, tissue repair, and stable-to-improved functional measures — evidence supporting a mutation-independent therapeutic approach.
RAG-18 advances to higher dose as Cohort 2 completes enrollment
RAG-18, built on Ractigen's RNAa platform and delivered via the company's Lipid-Conjugated Oligonucleotide (LiCOTM) technology, is administered as a monthly intravenous infusion targeting the UTRN gene without viral vectors or permanent DNA editing. The compound holds Orphan Drug Designation and Rare Pediatric Disease Designation from the FDA. Cohort 2, testing a 30 mg monthly dose, is now fully enrolled, with safety follow-up proceeding as planned under trial NCT07282652.