Repurposing medication, Advancing delivery, and Deploying Innovative Chemistry to Aid the Lives of patients with Congenital Disorders of Glycosylation

• Applicant: Professor Dr. Uwe Kornak
• Subject Area: Endocrinology, Diabetology, Metabolism ; Human Genetics ; Pediatric and Adolescent Medicine ; Pharmacology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 583957229

Congenital Disorders of Glycosylation (CDG) are a heterogeneous group of ≈ 200 disorders, often with severe neurodevelopmental symptoms. As inborn errors of metabolism, they are usually caused by deficiencies of cellular enzymes or transporters and lead to disease because of shortage or overabundance of specific molecules. Very few CDG are treatable: compounds potentially best suited as treatments are often water soluble or unstable and cannot reach the required intracellular compartments. RADICAL-CDG assembles a pan-European network of key national hubs for CDG diagnosis, research, and care, while simultaneously forming close partnerships with patient organizations. As well as the development of novel therapeutic strategies using cell, organoid, and animal disease models, it will improve the lives of CDG patients via inclusion, and increasing access to credible, up-to-date information on research progress. It will employ three complementary scientific approaches: (i) drug repurposing, (ii) pathophysiology-driven drug development, and (iii) innovative drug delivery methods, alongside iv) a strategic framework for inclusion of patient organizations. Research will focus on the following CDG types: 1. PMM2-CDG: ≈50% of CDG cases. We will explore nanoparticle-based drug delivery systems and therapies targeting oxidative stress, a key pathological feature. 2. Neutropenia in G6PC3- and G6PT-deficiencies (secondary CDG): Currently managed with SGLT2 inhibitors, we propose that SGLT5 inhibitors may offer superior efficacy. 3. NANS-CDG: Caused by defective sialic acid synthesis, we will evaluate synthetic sialic acid analogues and a strategy to reduce toxic intermediate accumulation. 4. Dolichol synthesis defects: We will test approaches to supplement missing dolichols and reduce toxic polyprenal accumulation. 5. GORAB-related gerodermia osteodysplastica: We will repurpose an antibody that is currently used to enhance bone formation in age-related osteoporosis.

• DFG Programme: Research Grants
• International Connection: Belgium, Czech Republic, France, Netherlands, Spain
• Co-Investigator: Privatdozent Dr. Christian Thiel
• Cooperation Partners: Professorin Hana Hansíková, Ph.D.; Dr. Elodie Lebredonchel; Professor Dirk Lefeber, Ph.D.; Professor Gert Matthijs, Ph.D.; Professorin Dr. Belén Pérez; Professorin Dr. Maria Veiga-da-Cunha