Thrombotic microangiopathy (TMA) is a rare but devastating disease where small blood vessels in the kidney become blocked, ultimately leading to acute kidney failure.

For decades, outcomes were bleak, until research undertaken in Newcastle and partly funded by the NCKRF transformed the field with the discovery that over-activation of the complement system, a part of the immune defence, drives many cases of TMA. This led to the successful introduction of eculizumab, a drug that blocks complement activation. For patients, who respond, this is life-changing, a disease that was previously fatal, can now be managed. Unfortunately, not all patients respond. 

Despite the progress we have made, we still don’t know how complement damages the kidney. Which cells are driving disease? What are the critical downstream events? Are there better treatment options that could be used for all patients with TMA.

To answer these questions, we will bring together Newcastle’s unique experimental model with a cutting-edge technology: spatial transcriptomics. This approach creates a molecular “map” of the kidney, showing which genes are active in which cells and where damage is occurring. Unlike older methods, it allows us to study disease in context capturing the precise chain of events as TMA lesions develop.

This project has the potential to redefine our understanding of TMA. By uncovering the cellular and molecular pathways that drive damage, we will identify new targets for therapy,  not only for complement-mediated disease but potentially all forms of TDA where no treatiment currently exists.