Project: CHAnging Rare disorders of LysInE metabolism

Acronym CHARLIE (Reference Number: EJPRD20-084)
Project Topic Rare inborn errors of lysine metabolism such as pyridoxine-dependent epilepsy (PDE) and glutaric aciduria type 1 (GA1) cause debilitating, often progressive neurologic symptoms. Although early detection via better diagnostics and newborn screening enables initiation of a medical diet, this therapy is often not effective resulting varying outcomes and considerable disease burden. Our international CHARLIE project synergizes the expertise of GA1 and PDE patient representatives, basic and clinical scientists, to collaboratively identify biomarkers, new disease mechanism, and importantly develop and test new therapies. One strategy inhibits the upstream enzyme, with the potential to reduce build-up of damaging metabolites thereby preventing brain damage. We will first apply this genetic therapy in PDE and GA1 model systems, such as neuronal stem cells and mouse models. Furthermore, we will investigate gene therapy to rescue the deficient GA1 enzyme and reduction of highly reactive toxic molecules in PDE. To evaluate and compare the efficacy of these different treatment approaches, we will perform behavioral, biochemical, morphological, enzymatic, untargeted metabolomics analyses. With our patient advocacy organizations, we will prioritize the most promising treatment strategy/-ies as well as enhance trial readiness. To inform the families, professionals, and stakeholders, we will organize regular meetings. Together we will pursue knowledge translation from bench to bedside, e.g. clinical trials and drug access, towards improved outcomes for PDE and GA1 patients and families.  
Network EJP RD
Call 2nd EJP RD Joint Transnational Call for Rare Diseases Research Project (JTC 2020)

Project partner

Number Name Role Country
1 Radboudumc Coordinator Netherlands
2 Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) Partner Spain
3 CMMT Partner Canada
4 TUM School of Life Sciences Weihenstephan Partner Germany
5 Centre for Child and Adolescent Medecine Partner Germany
6 Radboudumc Partner Netherlands
7 Luxembourg Centre for Systems Biomedicine Partner Luxembourg
8 Meyer Chilndren’s Hospital Partner Italy
9 Selbsthilfegruppe Glutarazidurie ev. Partner Germany
10 Vereniging Volwassenen, Kinderen en Stofwisselingsziekten Partner Netherlands
11 Familias GA1 Partner Spain