Funded by the European Rare Diseases Research Alliance (ERDERA), HypoGluTx aims to treat rare neurodevelopmental disorders by targeting shared glutamatergic synapse dysfunction rather than studying each disease separately. The project, that has just celebrated its kick-off meeting, is entitled “Repurposing glutamatergic synapse therapies across rare neurodevelopmental disorders” (HypoGluTx) and has secured more than 1 million € in funding.
Coordinated by Xavier Altafaj, researcher at the IDIBAPS and the Institute of Neurosciences of the University of Barcelona, the new multinational project was selected within ERDERA’s first Joint Transnational Call 2025 and chosen from a highly competitive pool of 161 initial proposals, being among just 18 projects funded in ERDERA’s first call.
Targeting a common biological mechanism across rare disorders
Rare neurodevelopmental disorders are often caused by mutations in different genes, yet many converge on common mechanisms affecting synaptic formation and communication. HypoGluTx focuses on genetic disorders caused by mutations in GRIN2B, SHANK3, STXBP1 and CACNG2 genes, primarily disturbing glutamatergic synapse function, ultimately leading to neurodevelopmental disorders associated with a clinical spectrum including epilepsy, autism spectrum disorder traits (ASD) and intellectual disability. By studying these disorders side-by-side, HypoGluTx aims to identify shared molecular and cellular alterations that can be targeted therapeutically across multiple diagnoses.
Accelerating Treatment Development Through Drug Repurposing
A key objective of HypoGluTx is to test whether existing drugs and nutraceuticals with established safety profiles can be repurposed to restore synaptic function. Drug repurposing can shorten development timelines and reduce costs, compared with creating entirely new therapies from scratch.
To achieve this, the consortium will combine complementary experimental platforms, including patient-derived neuronal cultures, genetically engineered mouse models, preclinical-clinical biomarkers molecular profiling and high-throughput drug screening. Overall, this project will delineate how individual gene mutations affect glutamatergic excitatory neurotransmission and to assess whether personalized treatments can rescue neuronal dysfunction, across disease groups.
A collaborative Europe-wide effort with patient involvement at the core
HypoGluTx brings together a Europe-wide team of academic partners alongside patient organizations, ensuring that the research remains both scientifically rigorous and aligned with real patient needs. Beyond the coordination of the UB, the consortium includes 4 additional academic teams from the Universitat de Vic-Universitat Central de Catalunya (UVIC-UCC) through the Institut de Recerca i Innovació en Ciències de la Vida i de la Salut a la Catalunya Central (IRIS CC), the Centre for Innovative Biomedicine and Biotechnology/Center for Neuroscience and Cell Biology of the University of Coimbra (Portugal), VU University Amsterdam and Amsterdam UMC (The Netherlands), and the National Research Institute for Agriculture, Food and Environment (INRAE, France). Noteworthy, representative European Patient Association Organizations are key actors of the proposal, including GRIN Europe, European STXBP1 Consortium, STTXBP1 Poland and Associação Phelan-McDermid Portugal. All of them were present in this first meeting in Barcelona, held on May 28/29 at the University of Barcelona (UB) Medical Faculty, located in the heart of the Hospital Clínic in Barcelona.
By integrating expertise across disciplines and countries, the project aims to generate actionable preclinical evidence and support the development of a shared therapeutic platform that could benefit multiple rare neurodevelopmental disorders.
“Until now, research into rare neurodevelopmental disorders has mostly addressed these conditions individually, rather than the common biological roots that connect them. HypoGluTx embraces a holistic vision: rethinking these conditions through the shared lens of glutamatergic synapse dysfunction. By uniting patient associations with world-class, multidisciplinary academic teams, this initiative aims to reveal pathophysiological mechanisms that transcend individual diagnoses and to open new therapeutic horizons through drug repurposing" says Prof. Altafaj, coordinator of the consortium.
