Genotypic and phenotypic insights to advance pharmacological strategies in TBC1D8B steroid-resistant nephrotic syndrome

This project has been funded thanks to the Joint Call Fondazione Cariplo and Fondazione Telethon 2025.

Steroid-resistant nephrotic syndrome (SRNS) is a life-threatening kidney disease that affects both children and adults and is a leading cause of kidney failure worldwide. Unlike other types of kidney disease, SRNS does not respond to common steroid treatments, making it particularly difficult to treat. People with SRNS have high levels of protein in their urine (proteinuria) and scarring of the kidney tissue (focal and segmental glomerulosclerosis, or FSGS). Recent discoveries have shown that genetic mutations in the TBC1D8B gene cause SRNS. However, the exact role of this gene and how its mutations contribute to SRNS remains poorly understood, limiting effective treatments and support for patients. This project aims to fill this gap by investigating how specific genetic mutations are linked to SRNS symptoms and uncovering treatments tailored to individual cases. Using advanced technology, we have identified pathways and interactions within cells that are affected by these genetic mutations. we has also found that different mutations have different effects, which may contribute to the difficulty in identifying new therapeutic options. However, more work is needed to understand how these genetic changes drive the disease. Through advances in genetic research, scientists have discovered more than 50 genes associated with SRNS, providing new insights into its causes. By studying these genetic mutations and their effects on kidney cells, this project will create better models to develop new, targeted treatment strategies, offering hope to those affected by this challenging condition.