Detailed analysis of cell culture and zebrafish models to identify new therapeutic options for the hereditary disease hypophosphatasia.

• Applicant: Dr. Daniel Liedtke
• Subject Area: Developmental Biology ; General Genetics and Functional Genome Biology ; Cell Biology
• Term: since 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 397519724

This application is a follow-up application of the previous DFG-funded project and is intended to complete the analysis of the previously established cell culture and zebrafish models. Our main intention is to analyze previously insufficiently understood molecular consequences in hypophosphatasia patients and to tackle currently untreatable symptoms. In the case of hypophosphatasia, there are primarily osseous effects described within the clinical spectrum, such as mineralization disorders of the bones, which have been extensively analyzed scientifically and can be treated with enzyme replacement therapy. However, some aspects of the osseous effects are only partially understood or can hardly be treated, such as craniosynostosis and tooth/jaw pathologies. Similar to these, extraosseous symptoms, as well as neurological and sensory problems, have so far only been analyzed rudimentarily and can currently hardly be treated in patients. Moreover, these special HPP symptoms could not be fully elucidated and reproduced in any of the previously established animal models. We are convinced that our newly developed zebrafish models can make a central scientific contribution to the clarification of these aspects and provide previously missing pre-clinical/in vivo insights. The clarification of open molecular-biological questions in connection with a new hypophosphatasia model in zebrafish are intended to provide a better understanding of the disease itself, but should above all help to develop new therapy options for patients.

• DFG Programme: Research Grants