AADC Deficiency

Researchers are evaluating the safety and effectiveness of AAV2-hAADC gene therapy delivered directly into specific brain regions in children with aromatic L-amino acid decarboxylase AADC deficiency. This condition causes severe motor function loss and dystonic movements. The study is designed as a Phase 1, open-label, dose-escalation trial to determine the appropriate dose for future studies and to assess safety and clinical outcomes. Participants will receive AAV2-hAADC through an MRI-guided infusion into the substantia nigra pars compacta and ventral tegmental area of the midbrain. The study involves multiple cohorts receiving increasing doses, starting with a low dose in Cohort 1 and higher doses in subsequent cohorts. Infusions are delivered bilaterally at specific brain sites, with dosing intervals and volumes adjusted based on age and safety monitoring. The treatment phase includes follow-up assessments up to two years post-surgery. Throughout the study, participants will be closely monitored for adverse events related to surgery and gene therapy, with brain imaging and laboratory tests to evaluate safety. Clinical responses will be assessed using measures of motor function, symptom diaries, and various developmental and quality of life scales. Follow-up includes cerebrospinal fluid neurotransmitter analysis and PET imaging to assess biological activity. Participants may join a long-term follow-up study to monitor ongoing safety and clinical status.

The trial focuses on patients with Aromatic L-amino acid decarboxylase AADC deficiency, a rare genetic disorder affecting the production of important neurotransmitters dopamine and serotonin. Researchers are evaluating the safety and effectiveness of VGN-R09b, a gene therapy delivered directly into the brain, to improve symptoms related to this condition. This early phase clinical study aims to provide preliminary evidence for this treatments impact on patients with AADC deficiency. Participants will receive VGN-R09b through injections into the bilateral putamen area of the brain using stereotactic surgery. The study includes a dose-escalation phase followed by a dose-expansion phase to assess different dose levels. This open-label, single-center trial monitors patients after receiving the gene therapy to understand its effects and tolerability. During the study, participants will be closely monitored for adverse events and their motor development milestones, such as head control, sitting independently, standing or stepping with support, and walking with minimal assistance, over a period of 52 weeks. Researchers will conduct various assessments and follow-ups to track the treatments safety and effectiveness, with the overall participation lasting about one year.