Systematic Review: Drug Repositioning for Congenital Disorders of Glycosylation (CDG)

Advances in research have boosted therapy development for congenital disorders ofglycosylation (CDG), a group of rare genetic disorders affecting protein and lipid glycosylation andglycosylphosphatidylinositol anchor biosynthesis. The (re)use of known drugs for novel medicalpurposes, known as drug repositioning, is growing for both common and rare disorders. The latestinnovation concerns the rational search for repositioned molecules which also benefits from artificialintelligence (AI). Compared to traditional methods, drug repositioning accelerates the overall drugdiscovery process while saving costs. This is particularly valuable for rare diseases. AI tools haveproven their worth in diagnosis, in disease classification and characterization, and ultimately intherapy discovery in rare diseases. The availability of biomarkers and reliable disease models iscritical for research and development of new drugs, especially for rare and heterogeneous diseasessuch as CDG. This work reviews the literature related to repositioned drugs for CDG, discovered byserendipity or through a systemic approach. Recent advances in biomarkers and disease models arealso outlined as well as stakeholders' views on AI for therapy discovery in CDG.