On November 13, 2024, the FDA approved Kebilidi, a groundbreaking gene therapy for treating aromatic L-amino acid decarboxylase (AADC) deficiency, which was previously considered untreatable.

AADC deficiency is a rare genetic disorder that typically manifests in infants, severely impacting their physical, mental, and behavioral functions.

Christina Pacak, a molecular biologist, notes that the surgical delivery method enhances safety by allowing for lower dosages and minimizing systemic exposure, although it requires advanced surgical facilities.

The delivery of Kebilidi involves a minimally invasive surgical procedure where neurosurgeons inject the therapy directly into the putamen, a brain region essential for regulating movement, using a 3D positioning system.

Guangping Gao emphasizes that the central nervous system is an ideal target for gene therapies, allowing for long-term expression from a single dose due to the non-dividing nature of neurons.

The FDA's approval was bolstered by a global clinical trial that demonstrated the therapy's safety and efficacy, with ongoing studies to monitor its long-term effects.

The blood-brain barrier presents challenges for gene therapy delivery, necessitating direct injections or the use of specific AAV serotypes that can effectively bypass this barrier.

Kebilidi works by delivering the human dopa decarboxylase (DDC) gene, crucial for the production of neurotransmitters like dopamine and serotonin that facilitate neuronal communication.

The therapy's approval in the U.S. follows the earlier approvals of eladocagene exuparvovec, marketed as Upstaza, in the UK and EU in 2022, based on positive clinical trial outcomes involving 26 patients.

Long-term follow-up from clinical trials demonstrated significant improvements in patient mobility, with some individuals regaining the ability to walk within three years after receiving the therapy.

The success of Kebilidi could pave the way for the development of additional gene therapies aimed at treating other neurological conditions.

Kebilidi is the first adeno-associated virus (AAV) gene therapy designed for direct delivery into the brain, specifically targeting children and adults with AADC deficiency.