Third Party Funds Group - Sub project
Start date : 01.11.2022
End date : 31.10.2025
In FSGS it is often unclear if the basis of podocytopathy is a stress response of podocytes to circulating factors or the result of a second hit due to an underlying genetic predisposition. This leads to a therapeutic “try and error” scenario and based on standard regimens one treatment option is followed by another until a clinical remission can be achieved. Therefore, the development of patient-specific tools including humanized animal models and patient-derived cells is essential to define the best individualized treatment regimen. Personalized treatment options and cell-type specific targeting are of great interest for these patients to avoid systemic side effects of unnecessary drugs. We will approach primary and genetic FSGS with innovative methods including 3D glomerular coculture, zebrafish models, novel imaging techniques and nanoparticle technology in our interdisciplinary network. To identify permeability factors that might play a role in primary FSGS we will use raman spectroscopy and mass spectroscopy on serum, urine and kidney tissue to generate a personalized molecular fingerprint of the disease. We will use our zebrafish model to investigate functional and structural effects of FSGS sera as well as response to immunosuppressants in an individualized high throughput screening. If genetic FSGS is suspected or confirmed we will use fibroblasts generated from FSGS patients’ skin biopsies, reprogram them into stem cells and differentiate them into podocytes that keep the patients’ mutations as a personalized in vitro model to study effects of different immunosuppressive drugs ex vivo. Furthermore, we will evaluate the use of nanoparticle assisted drug delivery to target podocytes specifically in vivo in our zebrafish model. We will define a diagnostic pathway to optimize treatment options of individual patients and to development study protocols for FSGS subtypes more patient-centred than current KDIGO guidelines.