Nebulized MSC-Exos for Anti-MDA5+ RP-ILD: Safety and Efficacy Trial

Overview

Objective: To assess the safety, tolerability, and efficacy of nebulized MSC-exos-P1 in patients with anti-MDA5 positive dermatomyositis-associated rapidly progressive interstitial lung disease (RP-ILD). Design: Prospective interventional trial with 10 eligible patients aged 18-75, meeting criteria for RP-ILD and anti-MDA5 positivity. Primary endpoint is safety and tolerability, measured by adverse events within 30 days post-treatment. Secondary endpoints are clinical improvements on days 14 and 28, including serological indicators and chest HRCT scores. Exclusions: Pregnant/breastfeeding individuals, severe allergies, active pulmonary infections, pulmonary embolism, extracorporeal support treatments, and other specified conditions. Treatment: Nebulized MSC-exos-P1 daily for 14 days, plus standard care of corticosteroids and immunosuppressants. Monitoring: Regular vital signs, oxygenation index, and pulmonary function tests. Follow-ups at multiple points up to 12 months.

This single-center, prospective interventional trial aims to evaluate the safety profile and potential efficacy of nebulized mesenchymal stem cell-derived exosomes (MSC-exos-P1) in anti-MDA5 positive dermatomyositis patients with rapidly progressive interstitial lung disease. Anti-MDA5 positive RP-ILD represents a critical clinical challenge with mortality rates exceeding 50% despite aggressive immunosuppressive therapy, highlighting the urgent need for novel treatment approaches. The trial will enroll 10 eligible patients who will receive a 14-day course of daily nebulized MSC-exos-P1 while continuing standard immunosuppressive therapy. Safety monitoring will include daily vital signs, laboratory tests, and adverse event documentation during the treatment period. Efficacy assessments will measure changes in oxygenation parameters, pulmonary function, inflammatory biomarkers, and CT imaging findings at days 14 and 28 compared to baseline. The scientific rationale for this intervention is based on preclinical evidence demonstrating the immunomodulatory, anti-inflammatory, and anti-fibrotic properties of MSC-derived exosomes. These nanoparticles have shown the ability to modify alveolar macrophage phenotypes, reduce pro-inflammatory cytokine production, and suppress fibroblast activation - mechanisms that may directly target the pathophysiological processes driving RP-ILD in this patient population. The nebulized delivery system enables direct targeting of affected lung tissue while minimizing systemic exposure.