AADC Deficiency

Researchers are studying the safety and effectiveness of a gene therapy called AAV2-hAADC delivered directly to specific brain areas in children with aromatic L-amino acid decarboxylase (AADC) deficiency. This condition causes motor problems such as loss of movement and dystonia. The study focuses on safety by monitoring side effects, brain imaging, and lab tests, and also looks at how the therapy affects motor function and symptoms in these children. The treatment involves a single-stage, open-label dose-escalation where AAV2-hAADC is infused into targeted brain regions using MRI guidance. Participants are grouped into cohorts receiving different doses, starting with low doses and increasing based on safety reviews. Doses are delivered bilaterally into the substantia nigra pars compacta and ventral tegmental area. The study includes five cohorts varying by age and dose volume, with careful monitoring between dosing groups. During the study, participants undergo evaluations including motor function assessments, symptom diaries, brain scans like PET and MRI, and lab tests on cerebrospinal fluid. Researchers track adverse events related to surgery and treatment over two years. Additional measures include disability and quality of life assessments. Follow-up continues for two years, and participants may join a long-term study to monitor their safety and clinical status beyond the initial period.

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 treatment's 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 treatment's safety and effectiveness, with the overall participation lasting about one year.