May 14, 2026 —
Capsida Biotherapeutics has announced that it will close the SYNRGY Phase 1/2 clinical trial of CAP-002, its investigational AAV gene therapy for STXBP1-related developmental and epileptic encephalopathy, or STXBP1-DEE. The decision follows the death of the first patient treated in the trial in September 2025 and a subsequent clinical hold.
STXBP1-DEE is a rare genetic neurological disorder that can cause early-onset epilepsy, developmental delay, and significant neurological impairment in children. CAP-002 was being developed as a gene therapy approach intended to deliver treatment to the brain, with the goal of addressing the underlying genetic basis of the disease.
According to Capsida’s public update, the patient died from cerebral edema, or swelling of the brain. The company has not confirmed the underlying driver of the cerebral edema and stated that additional laboratory research is ongoing to better understand what happened. Capsida emphasized that the analysis is complex and will require more time.
In the update, Capsida also disclosed additional information about CAP-002’s delivery mechanism, stating that the AAV gene therapy engages with ADAM15, a transmembrane protein involved in cellular adhesion and cytokine processing. The company had hoped this interaction would help facilitate entry into the brain.
The case has intensified broader discussion around the safety of AAV gene therapy, particularly for CNS-directed programs, pediatric populations, vector design, dosing, immune responses, and manufacturing-related impurities. While third-party experts have suggested that vector-related impurities or immune activation could be possible contributors, Capsida has not confirmed a definitive cause.
The closure of the SYNRGY trial represents a serious setback for the CAP-002 program and for families seeking new therapeutic options for STXBP1-DEE. At the same time, the update underscores the importance of transparent safety reporting, long-term investigation, and careful risk assessment as the field continues to develop next-generation AAV delivery technologies for neurological diseases.
