Credit: Midjourney
Every year, a small number of babies are born, or don’t survive to be born, because of a disease their parents never knew they carried. Both parents are healthy. Both are carriers of a mutated gene they’ve had no reason to suspect. But when two copies of that mutation meet in a developing baby, the consequences can be catastrophic and swift.
Researchers at the University of Southern California believe they may have found a promising new path forward, and the starting point is something most people flush away without a second thought.
When the Kidneys Become the Enemy
Autosomal recessive polycystic kidney disease, or ARPKD, affects roughly 1 in 26,500 live births worldwide. In its most severe form, it is detectable before birth. Fetal ultrasounds, typically around week 20, reveal kidneys that have grown massively enlarged and riddled with fluid-filled cysts. The swollen organs leave no room for the lungs to develop.
“The kidneys get so big that it affects other essential organ development during fetal development, ,” said Eun Ji Chung, the study’s senior author and the Director of the Transformative Center for Nanomedicine Dr. Karl Jacob Jr. and Karl Jacob III Early Career Chair and an associate professor of biomedical engineering, chemical engineering, medicine, surgery, and pharmacy at the Alfred E. Mann Department of Biomedical Engineering at USC Viterbi. “When the severe form of ARPKD occurs, the patient is born, and oftentimes they’re unable to breathe. So, it’s not just a kidney problem.”
About 20% of affected newborns do not survive the first 24 to 48 hours. Many pregnancies are terminated following the ultrasound diagnosis. For children who do survive, the road ahead involves dialysis, strict dietary management, and often both kidney and liver transplants before adulthood. Approximately half of those who make it past the newborn stage will need a transplant by age 15 to 20.
Through all of it, there is not a single FDA-approved treatment specifically for ARPKD.
A Frustrating Medical Blind Spot
Part of the reason this disease has gone largely unaddressed comes down to the brutal arithmetic of rare disease research.
“There’s not enough people to do a clinical trial,” said Chung. Only about 5% of rare diseases have any FDA-approved therapy at all. ARPKD, despite its severity, remains firmly in the other 95%.
For Chung, that statistic has a human face. A few years ago, a cross-country cycling fundraiser brought PKD advocates through USC’s lab. Among those who stopped by were parents who had lost children to ARPKD. “You start to have that kind of personal connection,” she said. It was the kind of encounter that turns an interesting scientific problem into an urgent one.
Letters from Healthy Cells
The USC team’s approach starts with a biological mechanism that has nothing to do with pharmaceuticals or gene editing. Kidney cells naturally shed tiny membrane-enclosed particles called extracellular vesicles, and those particles end up in urine. These microscopic packages carry proteins, genetic material, and molecular signals from the cells that produced them. If the cell is healthy, the cargo reflects that.
Chung describes them simply: “You can just think of them as little packages that they send to neighbors to give them a message. And inside of it is very similar to what that parent has. So, if you have a healthy kidney cell, it’s going to send out packages that have healthy versions of that gene that’s mutated in the disease.”
In ARPKD, mutated genes fail to produce two proteins, fibrocystin and cystin, that are essential to normal kidney development. The team’s insight was that urinary vesicles from healthy donors naturally contain functional versions of those same proteins. The question was whether those vesicles, once collected and purified from healthy donors, could effectively resupply what the disease has taken away.
From a Mouse Model to a Womb
In laboratory tests, the answer was encouraging. Kidney cells deficient in cystin showed significant protein recovery after treatment with urinary vesicles. When the therapy was administered to mice bred to model severe ARPKD, the results were striking.
“This is what will be the very initial proof of concept for our novel treatment,” said Yi Huang, the study’s first author and a PhD researcher in Chung’s lab. “We have shown an increased probability of survival from 27 days to 34 days in mice, a 26% increase in lifespan.” Blood markers of kidney function also improved markedly.
Then the team pushed further. Because the most devastating cases of ARPKD begin before birth, they tested whether these vesicles could be delivered directly into the amniotic sac of pregnant mice. The particles reached the fetal kidneys. Levels of the missing protein rose.
“We took all the organs from the fetus and also the moms, and we did histology to confirm there’s no tissue damage on the tissues,” Huang said.
“There’s this potential to be able to mitigate the disease during fetal development,” said Chung. The immediate next step, she and Huang noted, is to determine whether that early intervention can actually allow affected animals to be born and survive, the crucial question the current study was not yet designed to answer. From there, the path to human trials would require studies in larger animals, including pigs, and eventually primates. “There’s a long way to go,” Huang acknowledged.
Beyond One Disease
The implications extend beyond ARPKD. Urinary extracellular vesicles naturally carry a wide variety of kidney proteins, and the team has already demonstrated a version of this approach for the adult form of polycystic kidney disease. In principle, the same delivery system could apply to other genetic kidney conditions.
“Our nanoparticles, the extracellular vesicles, carry more than just that specific deficient gene,” Huang explained. Conditions such as Alport syndrome, he noted, could eventually be candidates.
If the therapy ultimately works in people, Huang sees it as potentially transformative. “If this works, it’s going to increase the survival rate, even before birth, since that’s a huge rate where lots of kids don’t survive,” he said. “After they survive birth, I think there’s more chance for us to provide additional treatment to those newborns, and that will increase their survival probability.” He also noted that, given the genetic nature of the disease, patients would likely need consistent, ongoing treatment rather than a single intervention.
Scaling up for human use is also increasingly feasible. Unlike therapies derived from complex cell cultures, urine is abundant, non-invasive to collect, and can be processed in large volumes using established filtration technology. Repeated dosing in mice produced no detectable organ damage in any tissue examined.
There is still a long road ahead. Large animal studies, primate trials, safety profiling, and regulatory review all stand between this research and a patient. But for the families who receive that ultrasound diagnosis, the ones who had no idea they were carriers and had no reason to think this was coming, the promise of an intervention that could begin before a baby even takes its first breath is a different kind of horizon entirely.
Published on May 28th, 2026
Last updated on May 28th, 2026