Canavan Leukodystrophy and Its Biomarker PeriNAA: Integrative Analysis of the Peripheral N-Acetylaspartate Metabolism

Background: Canavan leukodystrophy is a rare, neurodegenerative disorder. Aspartoacylase (ASPA) deficiency prohibits N-acetylaspartate (NAA) breakdown and damages brain white matter. Patients show macrocephaly, severe psychomotor impairment and early lethality. Treatment options are only symptomatic. The physiological role of NAA is poorly understood. Reports point to an important role of NAA metabolism in peripheral tissues, e.g., in cancer cells. The goal of the research project PeriNAA is a detailed characterization of central and peripheral NAA metabolism.

Methods: After informed consenting, patient data on disease course and peripheral manifestations will be evaluated pro- and retrospectively. Clinical data and patients’ tissue samples will be forwarded to PeriNAA cooperation partners in Brunswick and Munich. Metabolism of primary and genetically altered cell lines as well as mouse and patient tissues will be investigated biochemically. The resulting data will be integrated and analyzed using computational modeling.

Results: The junior research network PeriNAA will be funded by the German federal ministry of education and research until August 2024 to investigate the physiological NAA metabolism as well as the pathophysiology of Canavan disease by integrative, system medicine approaches. The goal is to develop a predictive, statistical model of NAA metabolism. Until now, 40 datasets of patients, partially with biosamples, are available.

Conclusion: A better understanding of pathophysiology may allow treatment development for Canavan disease and potentially also for other diseases with an involvement of NAA. Due to rarity of Canavan disease, the project depends on the referral of Canavan patients by colleagues.

Publication History

Article published online:
28 October 2021