Polycystic kidney disease (PKD) is a genetic disorder where clusters of fluid-filled sacs called cysts grow inside the kidneys.
These cysts slowly get bigger and multiply, damaging the kidneys and making it harder for them to work properly. In the later stages of PKD, many people need dialysis because their kidneys can no longer function. Right now, there is no cure.
Researchers at UC Santa Barbara, led by Dr. Thomas Weimbs, are trying a new way to stop these cysts from growing.
They’ve designed a special kind of lab-made antibody that can go inside the cysts and block the signals that tell the cyst cells to keep growing. Their early findings, published in the journal Cell Reports Medicine, show promise for future treatments.
Cysts in PKD grow because the cells lining them produce growth signals that feed back onto themselves and nearby cells. It’s like a loop where the cells keep telling each other to grow.
The problem with many current treatments is that they either don’t work well or cause side effects, because the drugs can’t get inside the cysts where the damage is happening.
Standard antibodies used in cancer therapy are too big to enter these closed cysts. But Dr. Weimbs and his team focused on a smaller type of antibody called dimeric immunoglobulin A, or dIgA.
This type naturally exists in our body’s secretions like tears and saliva, and it has the special ability to pass through cell layers. The idea was to use this ability to carry a treatment into the cysts.
To test their idea, the researchers modified a common antibody by changing its structure so it would behave like dIgA. Then they targeted it at a specific receptor on the cyst cells known as cMET, which plays a key role in making the cells grow.
When tested in mice, the antibody successfully entered the kidney cysts and stayed there. It also reduced the activity of the cMET receptor and triggered cell death in the cyst cells—but not in healthy kidney cells.
This targeted approach is important because it could avoid the side effects seen with other treatments that affect the whole kidney or other organs. Delivering the treatment directly into the cysts means better results with fewer risks.
Although the work is still in the early research stage and not ready for human use yet, the findings are encouraging. The team is now looking at ways to test more versions of these antibodies and explore which growth signals and receptors are the best to target.
They also hope to combine different antibodies to see if a multi-approach treatment could work even better.
This research was supported by the National Institutes of Health and the U.S. Department of Defense, and involved several researchers at UCSB including lead author Margaret F. Schimmel and her colleagues.
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The study is published in Cell Reports Medicine.
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