Intranasal exosome therapy in Coffin-Siris syndrome: Clinical evaluation of three children

Coffin-Siris Syndrome (CSS) is a rare neurodevelopmental condition most often caused by pathogenic variants in the ARID1B gene, a key component of the SWI/SNF (SWItch/Sucrose Non-Fermentable) chromatin-remodeling complex. Despite multidisciplinary interventions, functional improvement in CSS remains limited. Exosome-based therapeutics have recently gained attention for their potential neuroregenerative and neuroprotective properties.

This case series included three children with genetically confirmed ARID1B-related CSS who received intranasal exosome therapy in addition to ongoing rehabilitation. Adaptive functioning was evaluated before and after treatment using the Vineland Adaptive Behavior Scales, Third Edition (Vineland-3). Post-treatment assessments were performed 4-6 weeks after completion of the final intranasal exosome treatment cycle. Following the therapies, all patients demonstrated increases in the Adaptive Behavior Composite (ABC) score. The mean score increased from 83.0 pre-treatment to 90.7 post-treatment, corresponding to a mean improvement of 7.7 points (approximately +9%). Improvements were observed primarily in communication, daily living, and socialization domains, while motor-related changes were more modest yet clinically observable. No adverse events were observed during treatment. Given the small sample size, retrospective design, and concurrent rehabilitation therapies, these findings should be interpreted cautiously.

These preliminary observations suggest that intranasal exosome therapy may represent a feasible and well-tolerated adjunctive approach to support adaptive functioning in children with CSS. Further controlled studies are warranted to confirm efficacy and elucidate the underlying mechanisms.