New antibody breakthrough offers hope to slow polycystic kidney disease progression

PKD cysts grow uncontrollably due to self-stimulating growth signals secreted into their fluid-filled interiors. Traditional immunoglobulin G (IgG) antibodies, successful in cancer therapies, can’t cross the cyst lining to halt this process.

However, the researchers redesigned an antibody to mimic dimeric immunoglobulin A (dIgA), naturally able to traverse epithelial barriers via polymeric immunoglobulin receptors. This allowed the antibody to enter cysts and target the cMET receptor, a key driver of cyst expansion.

The team first confirmed in-vitro that the engineered antibody retained its ability to bind cMET. Testing in mouse PKD models showed the antibody successfully penetrated cysts where it reduced cMET activity, dampening the growth signals. Notably, it triggered a striking increase in apoptosis (cell death) specifically in cyst-lining cells, without harming healthy kidney tissue.

While promising, this work remains preclinical. Challenges lie ahead, including collaboration to generate additional antibody variants and identification of other growth factor receptors to block. The researchers hope to explore combination antibody therapies and refine targets for maximizing disease slowing or reversal.

This breakthrough could open a new chapter in PKD treatment-offering a “magic bullet” to stop cyst growth at its source, delaying kidney failure and improving quality of life. Though clinical application is years away, these findings bring fresh hope to thousands battling this relentless disease.

REFERENCE: Margaret F. Schimmel, Bryan C. Bourgeois, Alison K. Spindt, Sage A. Patel, Tiffany Chin, Gavin E. Cornick, Yuqi Liu, Thomas Weimbs. Development of a cyst-targeted therapy for polycystic kidney disease using an antagonistic dimeric IgA monoclonal antibody against cMET. Cell Reports Medicine, 2025; 6 (9): 102335 DOI: 10.1016/j.xcrm.2025.102335