HIPSC-LCH

Advancing the understanding and treatment of Langerhans Cell Histiocytosis (LCH), a neoplasm of the blood, is the motivation underlying this project that aims to develop an effective treatment for this disease while at the same time using human cell culture instead of animal models, thereby replacing the need for animal testing. LCH is characterized by the abnormal accumulation of blood cells, that is caused by mutations in the MAPK signaling pathway. This disease has a broad clinical presentation, affecting various organs, with particularly severe forms in young children. While localized LCH may resolve spontaneously, disseminated forms carry a higher risk of mortality and morbidity. Currently, high-risk LCH is treated with multimodal chemotherapy or MAPK-pathway inhibitors, which, despite their high response rate, have limitations in preventing relapse. The primary goal of this research project is to develop an in vitro system for LCH, focusing on two crucial aspects: the role and efficacy of MAPK-pathway inhibitors in LCH treatment, and the mechanisms driving neurodegeneration associated with the disease. Embracing the 3R principle of Refining, Reducing, and Replacing animal experiments, the project will utilize patient-derived induced pluripotent stem cells (iPSCs). This approach will facilitate the study of the BRAFV600E mutation, commonly found in LCH, and its impact on cells. The research will investigate the effects of different MAPK-pathway inhibitors on mutated cells and explore how they can be used to cure LCH. Through state-of-the-art techniques such as high-throughput drug screening and live cell imaging, the team will analyze the dynamics of MAPK inhibition, cell migration, and cytotoxicity. This comprehensive approach will not only shed light on the disease`s biology but also identify potential drugs that can target mutated cells effectively. Furthermore, by reducing reliance on animal models, this research offers a more ethical and potentially more effective method of studying LCH. The insights gained from this study are expected to drive the development of targeted therapies, paving the way for new clinical trials, and improved treatment strategies for LCH in children.

No additional funding sources recorded.