Inhaled siRNA therapy targeting RAGE for pulmonary inflammation: a first-in-human randomized trial.

Inhaled ARO-RAGE siRNA safely reduces lung RAGE levels and pulmonary inflammation in humans, demonstrating effective target engagement in a first-in-human trial.

• Why it matters: Pulmonary RAGE amplifies immune responses in disorders like asthma and COPD, but targeted therapies are limited, creating a need for safe, effective interventions to modulate lung inflammation.
• What they did: Researchers developed ARO-RAGE, an inhaled siRNA targeting RAGE mRNA, tested in preclinical models for silencing efficacy, and then evaluated safety, pharmacokinetics, and pharmacodynamics in a randomized, placebo-controlled phase 1/2a trial involving healthy volunteers and asthma patients.
• The result: The therapy was well tolerated with no adverse effects, showed prolonged decreases in soluble RAGE levels indicating successful lung targeting, and supports further clinical development for pulmonary inflammatory diseases.