Treatment of IgA nephropathy
IgA nephropathy is a leading cause of chronic kidney disease and kidney failure. In the course of the disease IgA deposits build up in the kidneys, causing inflammation that damages kidney tissues. Pathological activation of the lectin pathway of the complement system by aberrantly glycosylated IgA molecules is a major cause of kidney damage. Activated lectin pathway components have been detected in over half of the IgA nephropathy patients’ kidney. Unfortunately, there is no disease-specific treatment for this severe condition.
Lectin pathway inhibition is a promising therapeutic option to treat IgA nephropathy. MASP-2 is an indispensable enzyme for lectin pathway activation, consequently, inhibition of the enzymatic activity of MASP-2 shuts down the lectin pathway activity. EvolVeritas has developed selective and efficient inhibitors against MASP-2 by directed protein evolution. These inhibitors completely prevented lectin pathway activation in in vitro and in vivo experiments. The selective MASP-2 inhibitors proved to be non-toxic in animals, while they provided long-term protection against lectin pathway mediated complement attack.