OBJECTIVES:

Aromatic L-amino acid decarboxylase deficiency (AADCd) is a life-limiting and acutely debilitating rare genetic neurological disorder that causes widespread central nervous system dysfunction and developmental delay. Eladocagene exuparvovec is a gene therapy, approved in Europe, which bilaterally delivers a functional DDC gene directly into the putamen improving patient motor function. Due to the disease rarity and paucity of surrounding data, clinician experts were surveyed on evaluating the importance of motor development in AADC deficiency progression and outcomes.

METHODS:

Twenty-four clinicians completed an online survey (2020) from various geographical regions (US, EU, Asia, ME, SA). Twenty-one clinicians provided feedback regarding disease proxies and motor milestone in relation with age, life expectancy, cognitive symptoms, resource utilization, and quality of life. Clinician specialties included paediatric neurology (81%, N=17) and metabolic disorders (19%, N=4). Most clinicians had direct experience treating AADC deficiency (71%, N=15).

RESULTS:

Clinicians agreed on the following points: 1. Given the lack of mortality data available the most severe form of Cerebral palsy (poor head control) is an appropriate proxy (67%, N=14); 2. Life expectancy is influenced by the achievement of motor milestones (95%, N=20); 3. Patient cognitive functioning and symptoms of OGC, dystonia and other behavioural aspects is adequate to relate with motor milestone improvements (92%, N=19); 4. Significant differences in resource utilization (e.g., frequency of neurology visits, psychological assessments, screening tests, etc.) should exist when comparing between different states of motor milestone (100%, N=21); 5. Patients with greater mobility are more likely to overcome complications, extend life and experience better quality of life.

CONCLUSIONS:

These data provide an understanding of AADCd and the importance of motor function in its progression and differential management. Eladocagene exuparvovec addresses motor function issues and is expected to improve patient outcomes. Finally, these results can be helpful in developing AADCd health economic models.