Defining pathogenetic mechanisms and exploring novel therapeutic approaches in Jamuar Syndrome

Jamuar syndrome is an ultra-rare developmental and epileptic encephalopathy, first identified in 2021, with approximately 40 patients reported worldwide. It is caused by biallelic pathogenic variants in the UGDH gene, which encodes an enzyme involved in glycosaminoglycan biosynthesis and in the organisation of the brain’s extracellular matrix (ECM). As the condition has only recently been described, knowledge of its underlying molecular mechanisms remains limited. Over three consecutive funded phases, our group has developed 2D and 3D neuronal models to study the disease using multi-omics and advanced analytical approaches. Work is currently underway to generate the first mouse model of Jamuar syndrome using CRISPR/Cas9 technology to investigate the disorder in a complex physiological context. Potential pharmacological approaches are also being evaluated within these experimental systems. This integrated activity combines biological investigation with preclinical assessment, aiming to lay the foundation for the development of future therapeutic strategies.