Patient selection considerations for AADC deficiency gene therapy

Area of Science:

• Neurology
• Genetics
• Rare Diseases

Background:

• Aromatic ʟ-amino acid decarboxylase (AADC) deficiency is a rare, severe neurological disorder.
• Caused by pathogenic variants in the DDC gene, leading to neurotransmitter deficiency.
• Characterized by motor, autonomic, and cognitive developmental impairments, with variable clinical presentation and increased mortality.

Purpose of the Study:

• To present considerations for patient selection for AADC deficiency gene therapy.
• To guide clinicians in identifying appropriate candidates for a new disease-modifying treatment.

Main Methods:

• Review of current clinical understanding and treatment landscape for AADC deficiency.
• Development of evidence-based criteria for gene therapy candidacy.

Main Results:

• Identified key clinical criteria for gene therapy selection.
• Emphasized the need for confirmed diagnosis, significant functional impairment, and informed consent.

Conclusions:

• Gene therapy offers a new treatment avenue for AADC deficiency.
• Careful patient selection is crucial for optimizing therapeutic outcomes.
• Criteria include genetic confirmation, motor/cognitive deficits, persistent symptoms, and informed consent.