SIMPATHIC
Research programme
The use of diverse iPSC-derived neurons to identify common screening targets
We are using neuronal cultures differentiated from human induced pluripotent stem cells (iPSCs) derived from the 9 neurological, neurometabolic and neuromuscular disorders studied in the SIMPATHIC consortium. We are focusing on common pathways across these diseases by employing image-based assays targeting common dysfunctional pathways (e.g. mitochondrial function) and by identifying common metabolic biomarkers. The development of these assays will be crucial for a drug screening scheme to identify repurposing candidates with the potential to be effective in several disorders. Two screening strategies will be deployed in parallel: a biomarker-based mass spectrometric screening and an image-based high content phenotypic screening. A selection of 2000 drugs will be screened on cellular models of the 9 disease and drugs with efficacy in several cellular models will be subsequently validated in more advanced disease models. Finally, we are establishing 3D brain organoid models on which to validate hit compounds identified in the screening molecular mechanisms.
Collaborating for accelerating drug discovery
SIMPATHIC’s concept of synchronous drug development for multiple rare disorders with shared symptoms and cellular phenotypes aims to accelerate drug discovery for rare diseases. We developed a drug screening scheme to identify repurposing candidates with the potential to be effective in several disorders. For this purpose SIMPATHIC brought together experts in rare diseases and drug screening from Germany (Heidelberg University, Univeristätsklinikum Tübingen & Uniklinik Düsseldorf), The Netherlands (Amsterdam UMC, Radboudumc Nijmegen), Canada (Children’s Hospital of Eastern Ontario, Ottawa), Greece (BIOVISTA & National Center for Scientific Research Demokritos), Portugal (University Lissabon), France (APTEEUS) and Luxembourg (University of Luxembourg).
Interested to collaborate or to use our drug discovery pipeline?
Given the lack of therapies for rare diseases and the length of conventional drug discovery pipelines, we wish to accelerate this path using iPSC neural model and drug repositioning approaches. We are looking to expand our expertise and community and collaborate to other rare disease researchers.
If you are a researcher using iPSC neural cells in 2D or 3D models for rare diseases, we are interested in hearing from you. Perhaps we can help each other in reaching a common goal for the benefit of the patient community! In addition, if you are interested in drug screening on your own neurological disease models or have compiled your own compound library, then explore our drug screening pipeline for neurological, neurometabolic and neuromuscular disorders.
