329 Radiographic Safety of MRI-Guided AAV2-AADC Infusion in Children With AADC Deficiency

INTRODUCTION: Aromatic amino-decarboxylase (AADC) deficiency is a rare inherited enzymatic disorder inhibiting dopamine and serotonin production, leading to severe developmental delay, hypotonia, debilitating oculogyric crises (OGCs), and lack of nuchal control. Traditional treatments have focused only on symptomatic relief. METHODS: An ongoing clinical trial enrolled 36 patients underwent bilateral midbrain CED of AAV2-hAADC, co-infused with gadoteridol, targeting the substantia nigra and ventral tegmental area. Infusions were monitored in real-time by intraoperative MRI. Serial pre-, intra-, and postoperative MR images were analyzed up to 36 months post-infusion. Qualitative reviews assessed brain parenchyma and surrounding tissues, focusing on midbrain structures, with T1- and T2-weighted MR datasets reviewed by independent interpreters, including a blinded academic neuroradiologist and the staff neuroradiologist from the study sites. RESULTS: Pre-, intra-, and post-operative MR imaging was performed, yielding 122 MRI image sets. No serious adverse events were attributable to the study drug. In 15 patients with =1 year follow-up, three showed small focal areas of increased T2 signal in the bilateral midbrain without significant procedural sequelae . No evidence of parenchymal or neuronal toxicity was found. Patients exhibited complete resolution of OGCs and significant developmental progress, including regained head control, ability to sit and walk, and limited speech. Clinical improvements correlated with increased cerebrospinal fluid dopamine metabolite homovanillic acid and enhanced 18FDOPA-PET signals in the caudate nucleus and putamen. CONCLUSIONS: The study demonstrates the safety and efficacy of midbrain CED-based, MRI-guided administration of AAV2-hAADC in children with AADC deficiency. Real-time imaging with gadoteridol ensured precise target cannulization and volumetric coverage, enhancing therapeutic distribution and safety. These findings support this delivery-imaging system for personalized treatment in neurological conditions, significantly improving clinical outcomes in AADC deficiency.