Polycystic kidney disease (PKD) is a hereditary disorder that leads to the formation of numerous fluid-filled cysts in the kidneys, ultimately impairing their function. Researchers at UC Santa Barbara have proposed a new therapy that aims to halt the growth of these cysts by utilizing monoclonal antibodies specifically designed for this purpose. This innovative approach addresses a pressing medical need, as there is currently no cure for PKD, and patients often face the prospect of dialysis in advanced stages of the disease.
The research, led by Thomas Weimbs, a biologist at UCSB, was published in the journal Cell Reports Medicine. Weimbs explained the challenges of PKD, stating, “The cysts just keep growing endlessly. And we want to stop them.” The goal is to introduce a treatment capable of penetrating the cysts and inhibiting their growth.
Current treatment options include small-molecule drugs, but the only available medication that shows some efficacy in slowing disease progression comes with significant side effects and potential toxicity to surrounding kidney tissues. Weimbs highlighted the limitation of the commonly used immunoglobulin G (IgG) antibodies, which are too large to enter the cysts and therefore cannot deliver therapeutic effects where they are most needed.
To overcome this obstacle, the research team focused on a different type of antibody: dimeric immunoglobulin A (dIgA). This antibody has the unique ability to traverse epithelial membranes, allowing it to access the interior of the cysts. The team’s earlier work in 2015 demonstrated that dIgA antibodies could bind to polymeric immunoglobulin receptors on epithelial cells, facilitating their entry into the cysts.
The latest study built upon this foundation, targeting the cell mesenchymal-epithelial transition (cMET) receptor, a key player in cyst progression. The researchers engineered the dIgA antibody by altering the DNA sequence of IgG to create a new backbone that could effectively target the cMET receptor. Following this, they tested the engineered proteins in mouse models and confirmed their ability to penetrate the cysts and remain localized.
Weimbs noted that the results were promising, indicating that the treatment successfully inhibited cMET activity, which in turn reduced cell growth signals within the cysts. Additionally, the therapy appeared to induce apoptosis, or programmed cell death, in cyst epithelial cells without adversely affecting healthy renal tissue.
While the research is still in preclinical stages, the findings could pave the way for novel therapeutic strategies for PKD. The next steps involve identifying potential partners interested in collaborating on PKD research, as well as securing access to the necessary facilities and technologies to further develop these antibodies.
“We can also combine different antibodies against different receptors at the same time,” Weimbs stated, emphasizing the potential for a multi-faceted approach to treatment. This strategy could enhance the effectiveness of therapeutic interventions by targeting multiple growth factors and receptors simultaneously.
As the study progresses, the team is focused on exploring various growth factors active in cyst fluids, which may offer additional avenues for therapeutic development. This research holds the promise of transforming the treatment landscape for polycystic kidney disease, potentially improving outcomes for patients affected by this challenging condition.
The research was conducted by a team that includes Margaret F. Schimmel as lead author, alongside Bryan C. Bourgeois, Alison K. Spindt, Sage A. Patel, Tiffany Chin, Gavin E. Cornick, and Yuqi Lu at UCSB. Further details can be found in the paper: “Development of a cyst-targeted therapy for polycystic kidney disease using an antagonistic dimeric IgA monoclonal antibody against cMET,” published in Cell Reports Medicine in 2025.
