Frameless intraputaminal delivery of gene therapy with eladocagene exuparvovec in patients with aromatic L-amino acid decarboxylase deficiency: safe and efficient results.

PURPOSE: We present two clinical cases of frameless, neuronavigated gene therapy with eladocagene exuparvovec for aromatic L-amino acid decarboxylase (AADC) deficiency in pediatric patients, detailing the targeted bilateral microdose delivery of viral vectors into the putamen and highlighting the feasibility and challenges of this approach in managing a rare neurometabolic disorder.

METHODS

Two patients with a confirmed diagnosis of AADCD underwent frameless stereotactic gene therapy. High-resolution 3 T MRI-guided trajectories were planned for the targeted bilateral putaminal infusion of 0.32 ml of eladocagene exuparvovec (AAV2-hAADC). The agent was delivered via a SmartFlow Neuro Ventricular Cannula in a "Z-pattern," retracting the cannula 2 mm every 9 min to achieve controlled microdosing.

RESULTS

Accurate frameless drug delivery was achieved in a shorter time than frame-based approaches, with no intraoperative or postoperative complications. One patient showed a small post-ischemic cyst on the 1-month follow-up MRI, without any neurological deficits. Over 2 months, both patients demonstrated reduced oculogyric crises, diminished hyperkinesis, and improved head control, with no significant adverse events.

CONCLUSION

Frameless, neuronavigated gene therapy for AADC deficiency proved both feasible and safe, with early clinical improvements observed in motor function and symptom control. This technique offers a promising alternative to frame-based methods and expands treatment options for this rare neurometabolic disorder.