The First Multi-Center, Multi-National Retrospective and Prospective Natural History Study of Canavan Disease

Objectives: Canavan Disease (CD) is a rare, autosomal recessive, leukodystrophy caused by aspartoacylase deficiency, leading to brain accumulation of its substrate N-acetylaspartic acid (NAA) and severe impairment of psychomotor development. CD progression can be most pronounced in the earliest months of life. There is a paucity of longitudinally collected data from CD patients and no approved therapies for CD exist. Advancing the understanding of CD and facilitating the development of therapeutic options requires a comprehensive, precise delineation of CD natural history. Therefore, the objective of this study is to rigorously collect data from CD patients, define endpoints for interventional trials, and identify gaps in disease management across ranges of ages and disease severity.

Methods: This multi-center natural history study will enroll pediatric CD patients for prospective, longitudinal collection of clinical data using standardized instruments and intervals on an observational basis and for retrospective collection of medical record data. As most classic CD patients do not obtain the ability to sit up, infant early development scales were chosen. Gross and fine motor development, cognitive development, quality of life, and general and disease-specific symptoms will be assessed. Beyond milestones, symptom occurrence will be extracted from medical records and assessed prospectively to populate a CD-specific disease scale. Quantitative brain imaging modalities will measure structure, morphology, and NAA.

Results: Demography and enrollment status will be presented.

Conclusions: The CD natural history study is enrolling and expected to continue for 3 years. The natural history database will be available for meaningful research towards treatment of CD patients.