West LA Times

UCLA researchers have made a significant discovery in the field of kidney disease, pinpointing type 5 collagen as a key determinant in kidney fibrosis. This finding has the potential to predict the progression of chronic kidney disease. The study, published in Science Translational Medicine, suggests that type 5 collagen could act as a biomarker for chronic kidney disease progression, paving the way for a precision medicine approach to treat high-risk patients.

The study reveals that the anti-cancer drug, Cilengitide, may reduce kidney scarring and slow disease progression in preclinical models. "Fibrosis, or scarring, is one of the strongest predictors of kidney failure," stated Dr. Arjun Deb, the study's senior author. "Our findings indicate that differences in type 5 collagen expression help explain this variation and that testing for expression of this gene or protein could identify people at greater risk."

Chronic kidney disease affects a substantial portion of the adult population in the United States and worldwide. Excessive fibrosis can impair kidney function, often resulting in dialysis or organ transplantation as there are no therapies that directly target or reverse fibrosis. The research, funded by various organizations including the National Institutes of Health, marks a step forward in understanding the genetic factors behind fibrosis severity.

Dr. Deb and his team used data from the UK Biobank to find a correlation between Col5a1 expression and chronic kidney disease risk. "This gave us a clue that, in humans, Col5a1 expression could potentially be used as a biomarker," Deb said. Experiments in mouse models further confirmed that lower Col5a1 levels resulted in more severe fibrosis.

The research team explored blocking the αvβ3 integrin pathway, which was found to activate excessive fibrosis. They used Cilengitide, a drug developed as an anti-cancer therapy, which showed promise in reducing kidney fibrosis in animals with low type 5 collagen. Dr. Deb noted the potential of repurposing Cilengitide, already deemed safe by the FDA, for treating kidney fibrosis.

Going forward, the team aims to develop a blood test to measure Col5a1 levels in human patients, assisting in identifying individuals at high risk for more rapid disease progression. "We can use a simple blood test to measure type 5 collagen levels and identify individuals who could potentially benefit from this drug," Deb commented.

The novel approach to treating fibrosis with Cilengitide has not been tested in humans and has not been approved by the Food and Drug Administration for this use. A patent application for this therapeutic approach has been filed by the UCLA Technology Development Group on behalf of the Regents of the University of California.

The study included contributions from several other UCLA authors, highlighting the collaborative effort in advancing potential treatments for kidney and possibly liver and vascular fibrosis.