Project Details
Projekt
A pre-clinical target validation and therapy studies pipeline for treating human Alport spectrum disease
Applicants
Professor Dr. Hans-Joachim Anders; Dr. Jan Böckhaus
Subject Area
Nephrology
Term
since 2026
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 583565980
Alport syndrome (AS) is a hereditary disorder caused by mutations in the COL4A3, COL4A4, or COL4A5 genes, important components of the glomerular basement membrane. The improper formation of the GBM network impairs kidney function and frequently leads to kidney failure during young adulthood. In absence of a cure, combining standard of care with selected small molecules 4-phenylbutyrate (4-PBA; improves mutant COLIV folding), finerenone (mitigates fibrosis/inflammation), and an A1M-based peptide (heme-binding antioxidant)- could synergistically mitigate CKD effects and preserve kidney function. Previous preliminary single-center data will be validated through multicenter pRCTs, a novel experimental tool to reliably predict the outcome of human trials, leveraging two established Col4a3 mouse models. In addition, our AI-driven and augmented target identification pipeline, validated via AS biopsy samples, patient-derived kidney cultures, glomerulus-on-a-chip, and biosamples, will uncover novel therapeutic targets for in vivo testing. Altogether, we will establish a preclinical drug identification and validation pipeline to select the most promising targets for selected clinical trials, as for this orphan disease only few trials can be conducted.
DFG Programme
Research Grants
International Connection
Cyprus, Italy, Netherlands, Sweden
