On a cold December night more than a decade ago, a snowmobile crash on a rural Iowa road left Chad Rockow with a shattered lower leg — and months of surgeries, setbacks and pain so severe he considered amputation.

Nearly 13 years later, he learned the accident had set something else in motion: a Mayo Clinic discovery of a hidden, inherited disease affecting his entire family.

"At the time, the accident felt like the worst thing that could happen," Chad says. "My career, my life, everything turned upside down. But now I see it as the best thing because it may have saved my life, my sister's life, my brother's life and my dad's."

Watch: Chad's story | Videography by Kevin Sullivan, Mayo Clinic

Journalists: Broadcast-quality video (3:37) is in the downloads at the end of this post. Please courtesy: "Mayo Clinic News Network." Read the script.

The reason for the phone call traces back to Chad's recovery. When his leg failed to heal properly, Chad came to Mayo Clinic for specialized care. During treatment, he enrolled in the Mayo Clinic Biobank, donating a blood sample and joining tens of thousands of volunteers helping researchers unlock the genetic roots of disease.

His leg eventually healed, and Chad returned to life on his Iowa farm, rarely thinking about the blood sample he had left behind.

A life-changing phone call

Nearly 13 years later, his phone rang.

On the line was a Mayo Clinic genetic counselor. Researchers had identified a rare inherited mutation in a gene called SDHD. The mutation is linked to paraganglioma-pheochromocytoma syndrome, a condition that can cause tumors to form, often without symptoms.

Some remain slow-growing for years. Others can become life-threatening if not caught early.

"I remember thinking, 'This can't be me,'" Chad says. "I had zero symptoms."

But as the counselor explained how the mutation is passed down, pieces of his family's history began falling into place.

Years earlier, his father had undergone surgery to remove tumors from his neck. Other relatives had faced similar diagnoses. One had suffered a devastating stroke after a tumor wrapped around a carotid artery.

Chad added his father to the call and gave permission to review decades-old medical records. There it was, buried in surgical notes: paraganglioma tumors.

"That's when the hair stood up on the back of my neck," Chad says. "Everything connected."

Follow-up clinical genetic testing confirmed the mutation across the family. His father tested positive first. Then Chad. Then his brother and sister — none of whom had any symptoms.

Targeted imaging revealed that the mutation had already left its mark on all four of them. Chad had three tumors in his neck, including one wrapped around a carotid artery.

His father's tumors have returned decades after his original surgeries. His sister has two tumors in her neck. His brother faces the most advanced disease, with multiple tumors, including a cancerous tumor near the skull and spine.

Chad and his brother have since undergone surgery at Mayo Clinic, with additional surgery planned for his brother. His father continues treatment there, and all four family members remain under specialized surveillance.

From biospecimens to breakthroughs

When the Mayo Clinic Biobank began enrolling volunteers in 2009, the sequencing technologies that would one day reveal Chad's mutation didn't yet exist.

"We never would have dreamed this was possible at that time to do the kind of research that we can do now," says Dr. Janet Olson, an epidemiologist who helped build the Mayo Clinic Biobank and now serves as its principal investigator.

"It took years to recruit the patients, collect the samples, extract the DNA and build the infrastructure," Dr. Olson says. Now we're getting back those gold nuggets, and Chad's story is a great example of one of those gold nuggets.”

What started as a research resource — linking blood samples, DNA and health data from thousands of volunteers — has become a powerful engine for discovery, supporting more than 500 studies.

Each sample contains layers of information such as DNA, serum, plasma and white blood cells, offering different windows into human health. Over time, when linked with medical records, these samples evolve into a powerful resource, enabling deeper understanding of disease, identifying risk and accelerating discovery.

One of the Biobank's most ambitious efforts focused on the DNA contained within those samples. Mayo Clinic Biobank Project Generation analyzed genetic data from more than 52,000 participants, searching for variants tied to 78 medically actionable conditions, including cancers and cardiovascular diseases where early detection can change outcomes.

The project ultimately identified Chad's mutation and has offered results to nearly 1,000 participants whose findings could directly affect their health.

A gold mine of discovery

Dr. Olson describes the Biobank as a "gold mine" built through years of scientific investment — and patient trust.

"It took years to recruit the patients, collect the samples, extract the DNA and build the infrastructure," Dr. Olson says. "Now we're getting back those gold nuggets, and Chad's story is a great example of one of those gold nuggets.”

Chad's story illustrates the vision behind Precure Research, Mayo Clinic's initiative to identify disease before symptoms appear and intervene earlier, when treatment has the greatest chance to change outcomes.

For Chad, the mutation may always be part of his family's story, but he hopes it will no longer define their future. For the first time in generations, his family can see it coming.

The post A shattered leg, a blood sample and a discovery that may have saved a family (VIDEO) appeared first on Mayo Clinic News Network.

Mayo Clinic scientists are pushing medicine beyond diagnosis, developing treatments for ultrarare genetic diseases while building a model that could accelerate the path to treatment for many more. 

Behind the glass walls of her Mayo Clinic neuroscience laboratory, Margot Cousin, Ph.D., watches tiny clusters of living neurons flicker across her computer screen. Magnified hundreds of times, the cells carry the genetic variant responsible for KCNK9 imprinting syndrome, one of the rarest neurological diseases in the world.

Dr. Cousin directs Mayo Clinic's N-of-1 Therapeutics Program, where scientists develop treatment strategies for diseases so rare they may affect only a single person. Each advance can help shorten the path for the next ultrarare disease, and the one after that.

"For decades, the greatest success we could offer many patients was finally putting a name to their disease," says Dr. Cousin, a clinical and translational scientist in Mayo Clinic's Center for Individualized Medicine. "A diagnosis is an extraordinary achievement, but it's no longer the end of the journey. The future of medicine is turning that diagnosis into a path toward treatment."

Watch: One patient at a time, Mayo Clinic takes on the world's rarest diseases

Videography by Kevin Sullivan, Mayo Clinic

Journalists: Broadcast-quality video (2:28) is in the downloads at the end of this post. Please courtesy: "Mayo Clinic News Network." Read the script.

The neurons glowing on Dr. Cousin’s screen came from a small skin sample donated by Summer Nagele, a 21-year-old from Illinois living with KCNK9 imprinting syndrome. Low muscle tone affects her movement, speech and eating. She has reduced lung function, tires easily, sometimes uses a wheelchair for longer distances, and underwent spinal fusion for severe scoliosis at 13.

Yet Summer has built her life around the very things the disease makes difficult. She sings the national anthem before cheering crowds, performs in musical theater, competes in eight Special Olympics sports — gymnastics is her favorite — and advocates for people with disabilities.

Another part of Summer's story is unfolding somewhere far quieter — under Dr. Cousin's microscope.

Fewer than 100 people worldwide are known to have KCNK9 imprinting syndrome. Many are children.

Dr. Cousin knows them by name.

A path beyond diagnosis 

For ultrarare diseases, the path to treatment is especially difficult. There may be only a handful of patients to study, little clinical evidence to guide trials and almost no commercial incentive to develop a therapy.

Dr. Cousin and her collaborators are using advances in genetics, disease modeling, molecular therapeutics and artificial intelligence to find another way.

Every potential treatment begins with a small sample of cells donated by the people Dr. Cousin and her team hope to help.

In the laboratory, researchers coax skin cells backward into stem cells and forward into the types of neurons affected by the disease. As the neurons begin communicating, the effects of the mutation come into view — a gene that is too active or a protein that doesn't function as it should.

Those living cultures also become a testing ground. Along the lab bench, Dr. Cousin and her team use precision pipettes to introduce potential therapies into tiny wells of neurons, then watch how the cells respond. Some are existing FDA-approved drugs being tested for a new purpose. Others are experimental genetic therapies developed specifically for the disease.

Turning discovery into a treatment strategy 

What began as an effort to understand KCNK9 imprinting syndrome is now evolving into an international push to develop the disorder's first treatment. 

In 2022, Dr. Cousin and her team identified 15 previously unknown genetic changes that cause the disease. Those discoveries provided definitive diagnoses for 21 families and established a stronger scientific foundation for understanding the condition.  

Earlier this year, the team launched a natural history study to follow people with KCNK9 imprinting syndrome over time and better understand how the disease progresses. That information could help researchers identify measures for future clinical trials and determine whether a potential treatment is making a difference. 

In the laboratory, the team is investigating antisense oligonucleotides as one possible treatment strategy. The molecules can be designed to alter how genetic instructions are carried out inside cells. Researchers are still working to better understand the mechanisms driving KCNK9 imprinting syndrome and developing cell models needed to test potential therapies. 

Families are helping drive that momentum. Among them are Melissa and Sean Kelley, whose 12-year-old son, Preston, has one of the most severe forms of KCNK9 imprinting syndrome. He communicates through an eye-gaze device and relies on a wheelchair. The Kelleys founded the KCNK9 Foundation, helping transform a small group of isolated families into a global research community. 

"We share a special bond that no one else really understands," Melissa says. "For all of us with kids who are affected, our hope is to see a therapy in our lifetime." 

That community recently came together in Dallas, where Dr. Cousin joined families, clinicians and researchers from around the world for the third Global KCNK9 Imprinting Syndrome Symposium. For one of the world's rarest disorders, bringing so many families into one room was a milestone in itself. 

Sean says those face-to-face encounters give researchers "a much more nuanced view" of the disease and the many ways it can affect patients.  

Summer and her parents were part of the group that traveled to Dallas. "We trust Dr. Cousin," says her mother, Autumn Nagele. "When Summer was invited to be a part of the research, we knew her participation would be meaningful." Her father, Michael Nagele, puts their relationship with Dr. Cousin more simply: "She's family now." 

Summer's thoughts are on the younger children with KCNK9 imprinting syndrome. 

"I want the younger kids to be able not to go through the stuff that I do," Summer says. 

Scaling hope for ultrarare diseases

The search for a KCNK9 treatment is one part of a much larger effort. Across other ultrarare diseases, Dr. Cousin and her collaborators are applying the same approach, and in some cases, have already carried it from laboratory research to experimental treatment.

In 2025, they helped deliver the first custom experimental genetic treatments for Autosomal Dominant Leukodystrophy (ADLD) to a Mayo Clinic patient. The rare, fatal neurological disease slowly destroys the brain's white matter, disrupting the pathways that allow different regions of the brain to communicate.

Dr. Cousin and her collaborators have since built a comprehensive ADLD program, bringing together an international disease study and a dedicated ADLD Clinical Care Center to better understand the disorder, expand access to expert care and prepare for future treatment trials.

One by one 

For Dr. Cousin, the significance of the work is measured in much more than data points on a screen.

That became especially clear during Summer's skin biopsy.

With Dr. Cousin beside her, Summer began naming all the other children she had met through the KCNK9 community. One by one, she called them out, as if bringing them into the room with her.

"I thought of all the kids that I'm helping," Summer says.

Some breakthroughs are measured in millions of lives. In Dr. Cousin's laboratory, they begin with one.

The Bigger Picture

The work aligns with Mayo Clinic Research's Clinical Impact initiative, which is accelerating the path from scientific discovery to clinical trials and patient care. For ultrarare diseases, that means creating a more direct route from understanding the biology of a disorder to developing and testing potential therapies.

The Beyond the Breakthrough special series goes inside Mayo Clinic research to meet the people advancing medicine and cures for patients.

For more stories like this, visit Beyond the Breakthrough. 

The post One patient at a time, Mayo Clinic takes on the world’s rarest diseases  appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — A liver disease affecting nearly 30% of adults worldwide is not a single illness but five biologically distinct subtypes, Mayo Clinic researchers have found. Each carries different risks for heart disease, liver failure, cancer and the need for liver transplantation.

The study, published in Nature Communications and conducted in collaboration with scientists at Virginia Tech, shows that metabolic dysfunction-associated steatotic liver disease has multiple pathways — some tied to obesity and diabetes, others driven by inherited genetic factors.

Notably, genetic subtypes are associated with a higher risk of progression to advanced liver disease, including in patients without typical metabolic risk factors.

The findings could help identify high-risk patients earlier and guide more precise screening and personalized treatment.

"When clinical and genomic data are analyzed together at this scale, you begin to see patterns of disease progression that would otherwise remain hidden," says Shulan Tian, Ph.D., co-senior author and a bioinformatician at Mayo Clinic. "Once you separate these subtypes, you can start to match treatments to the biology that's actually driving the disease."

Metabolic dysfunction-associated steatotic liver disease, formerly called nonalcoholic fatty liver disease, occurs when fat builds up in the liver. It often develops without symptoms but can progress to inflammation, scarring and irreversible damage. It is a leading cause of cirrhosis, liver cancer and transplantation worldwide.

Decoding liver disease at scale

To uncover these subtypes, researchers integrated genetic sequencing with detailed clinical data from more than 4,600 patients with the disease. The dataset spanned a wide range of measures — from liver enzymes, body mass index and lipid levels to coexisting conditions such as diabetes, depression and sleep apnea.

Using advanced computational modeling, the team identified groups of patients who shared underlying biological signals, defining distinct subtypes of the disease.

"What's emerging here is a way to systematically identify meaningful subgroups within complex disease," says Eric Klee, Ph.D., co-senior author and the Everett J. and Jane M. Hauck Midwest Associate Director of Research and Innovation. "It helps us map complex disease with such precision that we can begin to anticipate its course and intervene before the most serious damage occurs."

The discovery was powered by Mayo Clinic's Research Data Atlas, a platform that connects genetic data with patient records to reveal patterns across large populations — a system Dr. Klee helped build. A key component of the Atlas is the Tapestry Study, which has generated Mayo Clinic's largest collection of exome data from more than 100,000 participants. The dataset captures key genetic information that shapes how diseases develop and progress.

"This is exactly the kind of insight large-scale genomic research was built to deliver," says Konstantinos Lazaridis, M.D., the Carlson and Nelson Endowed Executive Director for the Center for Individualized Medicine who led the Tapestry Study and is a co-author of the research. "When you connect genetic data with detailed clinical information across large populations, you can start to redefine diseases in ways that directly impact patient care."

Liver disease's hidden effects across the body

The study also revealed links beyond the liver. For the first time, researchers found that specific subtypes are associated with conditions such as depression, sleep apnea and migraine, underscoring the disease's broad systemic impact across multiple organ systems.

Next, the team plans to test the approach in broader patient populations and explore how these subtypes respond to different treatments, including therapies such as GLP-1 receptor agonists.

First author Tahmina Sultana Priya, now a Ph.D. student at Virginia Tech, contributed to the research while at Mayo Clinic. For a complete list of authors, disclosures and funding, review the study.

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:  

• Kelley Luckstein, Mayo Clinic Communications, newsbureau@mayo.edu

The post 5 subtypes of common liver disease discovered — including rapidly progressing genetic forms appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — Mayo Clinic researchers have discovered that chemical signals produced by gut bacteria work together to control intestinal movement. One bacterial signal helps set the intestines in motion, while another primes gut cells to respond more strongly, amplifying the effect.

The research expands scientists' understanding of how the gut microbiome communicates with the body, moving beyond the traditional focus on individual bacteria or bacterial molecules.

The findings, published in the Proceedings of the National Academy of Sciences, point to a potential new direction for microbiome-based treatments: restoring combinations of microbial signals rather than targeting a single microbe or molecule. The strategy could have implications for constipation-predominant irritable bowel syndrome, a chronic condition marked by abdominal pain and constipation.

"The gut microbiome is made up of trillions of microbes producing a vast array of chemical messages that interact with cells throughout the digestive tract," says Purna Kashyap, M.B.B.S., a Mayo Clinic gastroenterologist, director of the Mayo Clinic Microbiomics Program and a senior author of the study. "Deciphering how those signals work in combination gives us a much more precise picture of what is disrupted in disease and what would need to be restored to recover normal function."

How bacterial signals work in combination

Researchers focused on two bacterial molecules: hypoxanthine and butyrate. Earlier Mayo Clinic research found lower levels of both in patients with constipation-predominant irritable bowel syndrome. That finding led researchers to a deeper question: How do these molecules affect intestinal movement?

In the new study, the researchers found that hypoxanthine prompts specialized cells lining the intestine to release serotonin, a chemical messenger that helps move food through the digestive tract. Butyrate works differently. It primes the cells to respond more strongly to hypoxanthine, amplifying the effect.

These specialized cells, called enterochromaffin cells, serve as hubs where different microbial signals come together. They help the gut receive and respond to multiple chemical messages at once.

Researchers followed that chain of events from what happens inside a single gut cell to how contents move through the intestines. They used laboratory-grown intestinal cells, miniature gut models called organoids, intestinal tissue and genetically altered bacteria to piece together each part of the process.

Gianrico Farrugia, M.D., president and CEO of Mayo Clinic and a co-author of the study, is a gastroenterologist whose research has focused on the mechanisms that control gastrointestinal function.

"We have an opportunity to move beyond managing the consequences of disease and toward restoring function for patients," Dr. Farrugia says. "That starts with answering the unanswered questions we see in our patients and following the biology until we understand the mechanism. With that depth of understanding, we can uncover new possibilities for treatment and ultimately advance new cures."

What's next 

Researchers next want to determine whether identifying combinations of microbial signals that are altered in individual patients could eventually help guide treatment. Future research will explore whether restoring complementary signals can improve intestinal movement, with the longer-term goal of developing more precisely targeted microbiome-based therapies.

The research was supported by the National Institutes of Health, Mayo Clinic Center for Individualized Medicine, Mayo Clinic Microbiome Program and other organizations. One or more of the investigators is an inventor of technology related to this research. For a complete list of authors, disclosures and funding, review the study.

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About Mayo Clinic  
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.  

Media contact:   

• Sharon Theimer, Mayo Clinic Communications, newsbureau@mayo.edu

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Mayo Clinic researchers are uncovering the earliest shifts in disease biology — long before symptoms appear — revealing how disease takes root and opening new possibilities to change its course. 

By the time a disease is diagnosed, it may have been developing silently for years. Along the way, the body leaves clues: proteins shift, metabolism changes, immune responses evolve, and environmental exposures leave measurable traces. Until recently, many of these early signals were impossible to detect.

Mayo Clinic researchers are now charting that hidden period between health and disease — a new frontier in medicine that could transform how conditions such as Alzheimer's disease, heart failure, pulmonary fibrosis, chronic liver disease and chronic kidney disease are identified and intercepted before symptoms emerge.

The new Mayo Clinic initiative, called Precure Research, brings together biospecimens, advanced biological data, environmental health research, longitudinal clinical data, wearable technologies and artificial intelligence (AI) to better understand how disease begins, predict risk earlier and create new opportunities for prevention.  

"Precure Research marks the beginning of the next era of scientific discovery and its translation into patient care."

Dr. Konstantinos Lazaridis

A glimpse of what's possible 

The initiative is already generating discoveries. Mayo Clinic scientists have identified inherited risks for cancer and cardiovascular disease in nearly 2,000 people — many of whom had no previous indication they were at risk. Other studies have shown that certain precancerous changes can be detected years before cancer develops. AI can help clinicians identify signs of pancreatic cancer years before diagnosis, while subtle biological changes linked to Alzheimer's disease begin decades before memory loss. Mayo Clinic researchers are using AI, genetics and wearable technologies to reveal inherited heart disease before heart failure.

"Precure Research marks the beginning of the next era of scientific discovery and its translation into patient care," says Konstantinos Lazaridis, M.D., the Carlson and Nelson Endowed Executive Director of Mayo Clinic's Center for Individualized Medicine and director of Precure Research. "We are building the analytical and clinical tools needed to investigate questions that medicine has long recognized but has not been able to fully answer in ways that directly benefit patients."

The invisible years before diagnosis 

The initiative combines data from genes, proteins, metabolites, clinical records, wearable devices and environmental exposures to create a comprehensive view of how health changes and disease develops over time.

Underlying Precure Research is a new Mayo Clinic research ecosystem designed to study health and disease at an unprecedented scale. The initiative aims to build Mayo Clinic's largest integrated collection of biospecimens and scientific and health data to accelerate disease prediction and prevention.

Biological samples become data, and data becomes insight into the mechanisms of disease. Those insights drive the discovery of new biomarkers and therapies while informing smarter clinical trials.

AI helps researchers power that transformation, analyzing billions of data points simultaneously to reveal patterns that would otherwise remain invisible.

"Genomics showed us the blueprint, the underlying architecture of human biology," Dr. Lazaridis says. "Now we're watching that structure in motion — shifting, adapting, unfolding over time, shaped by the world around us and inside us, ultimately influencing the unique lives we each live." 

A lifetime of exposures

Disease is shaped by more than genetics alone. Across a lifetime, environmental and lifestyle exposures leave biological changes that accumulate over time. Scientists call this the exposome: the sum of those exposures and their effects on human biology.

These influences range from air, water and diet to pollutants, heavy metals, pesticides, physical activity, sleep, stress, noise and light.

"The air we breathe, the food we eat and the places we live leave a biological imprint," Dr. Lazaridis says. "Understanding those accumulated influences is essential to understanding why disease develops in one person and not another."

Researchers can now measure many of these exposures directly in blood and other biospecimens. Early efforts focus on heavy metals, pesticides and microplastics, linking those findings with geographic data to better understand how the places people live may influence their long-term health.

The exposome also captures protective influences, including nutrients and bioactive compounds that may support resilience and regulate inflammation, aging and metabolism.

A new vision for medicine 

The initial focus of Precure Research includes diseases of the brain, heart, kidneys, liver, and lungs, and their intersection with biological pathways such as inflammation, oxidative stress, aging and metabolic dysfunction.

Its long-term aim is to extend healthspan — the number of years people live in good health, free from chronic disease and disability — by addressing the drivers of chronic disease.

Precure Research is part of Mayo Clinic's Bold. Forward. strategy to Cure, Connect and Transform healthcare — helping define a future where disease is identified earlier, understood more completely and intercepted before it takes hold.

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PHOENIX — Researchers have validated a genetic scoring tool that may help physicians diagnose idiopathic pulmonary fibrosis and identify which patients are at greatest risk for severe outcomes, including death or the need for a lung transplant. The findings come from a new international study of more than 570,000 people co-led by Mayo Clinic and Brigham and Women's Hospital.

Published in the American Journal of Respiratory and Critical Care Medicine, the study is one of the largest real-world evaluations of a polygenic risk score for idiopathic pulmonary fibrosis. The findings bring this genomic approach one step closer to clinical care.

"Polygenic risk scores add a new layer of biological insight into the prediction of pulmonary fibrosis and mortality outcomes, bringing us closer to a future where diagnosis, prognosis and treatment are informed by each patient's unique molecular signatures."

- Dr. Victor Ortega

Researchers analyzed genomic and electronic health record data from four major biobanks in the U.S. and U.K., including the Mayo Clinic Biobank and Mayo Clinic Tapestry. They calculated a polygenic risk score for each participant by combining the effects of more than 60,000 DNA variants associated with idiopathic pulmonary fibrosis. While each genetic variant contributes only a small amount of risk, together they reveal patterns of inherited susceptibility that would otherwise be difficult to detect.

The researchers then tested whether the score could identify patients with the disease and predict clinical outcomes.

People with high polygenic risk scores were nearly three times more likely to have the disease than those with lower scores. The genetic score became even more predictive as researchers applied increasingly specific definitions of the disease, suggesting the score may one day help distinguish idiopathic pulmonary fibrosis from other forms of interstitial lung disease.

Among patients with the disease, those with high genetic risk were 23% more likely to die or require a lung transplant, indicating the score may also help identify patients at greatest risk of poor outcomes.

"Every patient has a unique genetic blueprint that we can use to estimate risk for the development of disease," says Victor Ortega, M.D., Ph.D., a pulmonologist, associate director of Mayo Clinic's Center for Individualized Medicine in Arizona, and a co-senior author of the study. "Polygenic risk scores add a new layer of biological insight into the prediction of pulmonary fibrosis and mortality outcomes, bringing us closer to a future where diagnosis, prognosis and treatment are informed by each patient's unique molecular signatures."

"Showing that this approach works across more than half a million people receiving routine clinical care is an important step toward understanding how it can ultimately benefit patients."

- Dr. Christopher Grilli

Idiopathic pulmonary fibrosis causes irreversible scarring of the lungs that progressively limits a person's ability to breathe. More than 100,000 Americans are living with the disease, and an estimated 30,000 to 40,000 new cases are diagnosed each year, according to the National Institutes of Health.

Because its symptoms often resemble those of other interstitial lung diseases, diagnosis can be delayed until significant, irreversible lung damage has already occurred. Confirming the diagnosis sometimes requires an invasive lung biopsy to collect lung tissue. Researchers hope a noninvasive genetic test using DNA from a blood or saliva sample may help reduce the need for those procedures in selected patients.

"Most polygenic risk scores are developed in carefully selected research populations," says Christopher Grilli, Pharm.D., a researcher at Mayo Clinic's Center for Individualized Medicine and co-first author of the study. "Showing that this approach also works across more than half a million people receiving routine clinical care is an important step toward understanding how it can ultimately benefit patients."

If further validated, researchers envision genomic risk scores complementing imaging and other diagnostic tools to help physicians diagnose the disease with greater confidence.

This research aligns with Mayo Clinic's Precure Research initiative, which seeks to uncover the earliest biological changes associated with disease and translate those discoveries into clinical tools that improve diagnosis, personalize care and ultimately change the course of disease. As part of that effort, the Precure-Lung study, led by Dr. Ortega, is expanding Mayo Clinic's research into interstitial lung diseases, including idiopathic pulmonary fibrosis.

For a complete list of authors, disclosures and funding, review the study. 

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About Mayo Clinic 
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news. 

Media contact:  

• Kelley Luckstein, Mayo Clinic Communications, newsbureau@mayo.edu

The post Researchers chart a genetic path to diagnosing pulmonary fibrosis and predicting outcomes appeared first on Mayo Clinic News Network.

JACKSONVILLE, Fla. — Mayo Clinic researchers have identified a previously unrecognized way the kidneys regulate water balance — an advance that could lead to improved treatments for polycystic kidney disease (PKD) and other disorders. The study, led by Fouad Chebib, M.D., a nephrologist at Mayo Clinic, is published in the Journal of Clinical Investigation.

The findings build on decades of scientific understanding by revealing an additional pathway the kidney uses to control water balance. Until now, the body's ability to concentrate urine — and prevent dehydration — has been thought to depend primarily on the hormone vasopressin. Dr. Chebib's team discovered an alternative mechanism that operates independently of that system.

"The kidney's ability to regulate water is one of the most fundamental processes in the body," Dr. Chebib says. "It's not every day that you uncover a new way it carries out that function."

Polycystic kidney disease is a common inherited condition that causes fluid-filled cysts to grow in the kidneys over time, gradually reducing kidney function and often leading to kidney failure. It affects millions of people worldwide, including an estimated 140,000 people in the U.S. with the most common form, autosomal dominant PKD (ADPKD). Many patients eventually require dialysis or a kidney transplant.

Watch: 1940s-era drug shows new promise for kidney disease

Dr. Chebib's team studies how kidney cysts grow in PKD using lab-grown cell models. As part of that work, they tested compounds expected to worsen the disease process by increasing cellular signals linked to cyst growth. One of those compounds was probenecid, a drug first used in the 1940s to conserve limited supplies of penicillin by reducing its urinary excretion.

"We thought this drug would make the disease process worse," Dr. Chebib says. "Instead, it did the opposite."

Rather than promoting cyst growth, the drug slowed it. After repeating the experiments multiple times, the team realized they had uncovered something important.

Further investigation revealed that probenecid affects how kidney cells handle urate, a molecule commonly associated with gout. Inside the cell, urate acts as a signal — triggering a chain of events that helps move water channels to the cell surface. This allows the kidney to reabsorb water and concentrate urine without relying on vasopressin, the hormone traditionally thought to control this process.

"This represents a distinct pathway from what is described in traditional physiology models," Dr. Chebib says. "It demonstrates that the kidney has an additional mechanism to preserve water."

For patients with PKD, the discovery could address one of the biggest challenges of current treatment. The only approved therapy, tolvaptan, works by blocking vasopressin, which slows cyst growth but causes patients to produce very large amounts of urine — often 6 to 7 liters a day. That side effect can be difficult to live with and leads some patients to stop treatment.

In preclinical studies and a small clinical trial, adding probenecid reduced urine volume and nighttime urination while preserving the treatment's effectiveness.

After taking probenecid, patients' urine volume dropped by about 30% on average, and they went from waking up several times a night to urinate to about once per night. Many also reported improved quality of life.

"The goal is to preserve the therapeutic benefit of tolvaptan while reducing its burden," Dr. Chebib says.

Despite these promising results, researchers are not planning to rely on probenecid as a long-term solution. The drug is decades old, affects multiple systems in the body and is not widely available today. Instead, the team is using what they learned to design more targeted therapies.

"Probenecid helped us uncover the mechanism," Dr. Chebib says. "Our goal is to take this insight and develop therapies designed specifically for this pathway."

For Dr. Chebib, the work is rooted in early inspiration. He was drawn to kidney research after his father developed PKD.

"This has been a long and deeply purposeful journey," he says. "It started with a personal motivation and led to something that could ultimately benefit patients."

For a complete list of authors, disclosures and funding, see the study.

JOURNALISTS: Soundbites with Dr. Chebib are available in the downloads below.

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Sharon Theimer, Mayo Clinic Communications, newsbureau@mayo.edu

The post Researchers identify new kidney pathway with help from 1940s-era drug, may improve polycystic kidney disease treatment (VIDEO) appeared first on Mayo Clinic News Network.

A new era of medicine is emerging at Mayo Clinic — one that finds disease before symptoms appear 

ROCHESTER, Minn. — When Mayo Clinic researchers sequenced the genomes of 484 seemingly healthy adults, they found that about 13% carried a serious, previously unrecognized genomic risk — conditions those patients did not know about and that standard care would likely miss.

Nearly all participants, 98.6%, had at least one genetic finding, and for most, the results called for monitoring. The study, published in Genetics in Medicine, also takes a closer look at what it takes to turn those findings into the proper follow-up care.

Among the 13%, the actionable findings pointed to serious risks, including hereditary breast and ovarian cancer; Lynch syndrome, linked to colorectal cancer; cardiomyopathy; long QT syndrome; and amyloidosis.

"These are people traditional testing based on symptoms or family history would not identify," says Dr. Konstantinos Lazaridis, the Carlson and Nelson Endowed Executive Director of the Center for Individualized Medicine and senior author of the study. "This study helps define the blueprint for integrating genomic insight into care at scale — turning information into decisions that can change the trajectory of disease."

From discovery to care

Identifying the risk, it turns out, is the easiest part. Acting on it is far more complex. Nearly every case required clinical interpretation, documentation and communication. This work fell largely to genetic counselors, who reviewed results, prepared individualized summaries and helped guide next steps for patients and care teams.

"Genetic counselors are often the first people to share this kind of information with patients," says Jessa Bidwell, a certified research genetic counselor and first author of the study. "There can be surprise, anxiety, devastation, and at times relief at finally having an explanation. Our role is to meet people in that moment and help them understand what their health risks might be, based on the genetic finding, and their personal and family history."

Most participants with actionable findings followed through, completing referrals and connecting with primary care specialists. Yet fewer than half had a documented conversation with a primary care professional after receiving results — underscoring how difficult it remains to integrate genomic findings into routine care.

The study positions predictive genomic screening as both a clinical opportunity and a systems challenge. The science exists. Researchers and clinicians are still building the infrastructure to act on it consistently.

At Mayo Clinic, that infrastructure is beginning to take shape through an initiative called Precure. Genomic screening is one part of that initiative, which aims to detect disease earlier by combining genetic data with other biological signals.

"Precure is one example of a moonshot for human health at Mayo Clinic," says Dr. Lazaridis, who leads the initiative. "It reflects Mayo Clinic's commitment to move medicine beyond treatment and toward lasting wellness." - Dr. Lazaridis

Predicting disease before it begins 

Most diseases don't arrive without warning. They begin with small shifts in genes, molecules, proteins and immune signals that develop over time, often years before symptoms appear.

Precure is Mayo Clinic's enterprise-wide effort to detect those early signals and intervene sooner. Powered by advanced computing and artificial intelligence (AI), the initiative currently focuses on five organ systems — the brain, heart, kidneys, liver and lungs — studying conditions such as Alzheimer's disease, heart failure and chronic liver disease to better understand how they emerge and progress.

The work draws on expertise from across Mayo Clinic and is supported by Mayo Clinic Platform, which brings together large-scale patient data and advanced computing to enable scientists to study disease across populations.

"Precure is one example of a moonshot for human health at Mayo Clinic," says Dr. Lazaridis, who leads the initiative. "It reflects Mayo Clinic's commitment to move medicine beyond treatment and toward lasting wellness."

Precure is part of Mayo Clinic's Bold. Forward. strategy to Cure, Connect and Transform healthcare. The genomic screening study is an early demonstration of what that looks like in practice: science that doesn't wait for disease to announce itself, and a system already being built to act on what it finds.

For a complete list of authors, disclosures and funding information, review the study. 

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Julie Ferris-Tillman, Ph.D., Mayo Clinic Communications, newsbureau@mayo.edu

The post Mayo Clinic study finds 1 in 8 adults carries hidden genetic risk — and reveals what it takes to act on it  appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — A Mayo Clinic-developed artificial intelligence (AI) model can help specialists detect pancreatic cancer on routine abdominal CT scans up to three years before clinical diagnosis. It identifies subtle signs of disease before tumors are visible, when curative treatment may still be possible. The findings, published in Gut, mark a milestone in Mayo Clinic's multiyear research effort to enable earlier detection of one of the deadliest cancers.

The study validates this next-generation AI model using data and workflows that mirror clinical practice, including CT scans from multiple institutions, imaging systems and protocols.

Researchers used the AI model to analyze nearly 2,000 CT scans, including scans from patients later diagnosed with pancreatic cancer — all originally interpreted as normal. The system, called the Radiomics-based Early Detection Model (REDMOD), identified 73% of those prediagnostic cancers at a median of about 16 months before diagnosis — nearly double the detection rate of specialists reviewing the same scans without AI assistance.

The advantage was even greater at earlier time points. In scans obtained more than two years before diagnosis, the AI identified nearly three times as many early cancers that would otherwise go undetected.

Pancreatic cancer remains one of the deadliest cancers because it rarely causes detectable signs in its earliest stages. More than 85% of patients receive a diagnosis after the disease has already spread, and five-year survival rates remain below 15%, according to the National Cancer Institute. Projections show it will become the second-leading cause of cancer-related death in the U.S. by 2030.

"The greatest barrier to saving lives from pancreatic cancer has been our inability to see the disease when it is still curable," says Ajit Goenka, M.D., the study's senior author, and a Mayo Clinic radiologist and nuclear medicine specialist. "This AI can now identify the signature of cancer from a normal-appearing pancreas, and it can do so reliably over time and across diverse clinical settings." 

REDMOD measures hundreds of quantitative imaging features that describe tissue texture and structure, capturing faint biological changes as cancer begins to develop. The model is designed to analyze CT scans already obtained for other reasons — particularly in high-risk patients, such as those with new-onset diabetes — and flag elevated risk before any visible mass appears. 

The model runs automatically without time-intensive manual preparation. The team validated the model across CT scans from multiple institutions, imaging systems and protocols, demonstrating consistent performance beyond a single dataset.

The model's predictions also remained stable over time. In patients with multiple scans, the AI produced consistent results months apart, supporting its use for longitudinal monitoring and early detection. 

"This AI can now identify the signature of cancer from a normal-appearing pancreas, and it can do so reliably over time and across diverse clinical settings."  - Dr. Ajit Goenka

Researchers are advancing this work into clinical testing through Artificial Intelligence for Pancreatic Cancer Early Detection, or AI-PACED. This prospective study evaluates how clinicians can integrate AI-guided detection into care for patients at elevated risk. The study combines AI analysis of routine imaging with longitudinal follow-up to assess performance, including early detection, false positives and clinical outcomes. 

This research is part of Mayo Clinic's Precure initiative, which aims to predict and prevent disease by identifying the earliest biological changes in the body before symptoms begin. It also reflects Mayo Clinic's Clinical Impact strategy, accelerating the translation of discovery into patient care. 

The study was supported by the National Institutes of Health, the Hoveida Family Foundation, the Mayo Clinic Comprehensive Cancer Center and the Champions for Hope Pancreas Cancer Research Program of the Funk-Zitiello Foundation. 

For a complete list of authors, disclosures and funding, review the study. 

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About Mayo Clinic  
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.  

About Mayo Clinic Comprehensive Cancer Center  
Designated as a comprehensive cancer center by the National Cancer Institute, Mayo Clinic Comprehensive Cancer Center is defining the cancer center of the future, focused on delivering the world's most exceptional patient-centered cancer care for everyone. At Mayo Clinic Comprehensive Cancer Center, a culture of innovation and collaboration is driving research breakthroughs in cancer detection, prevention and treatment to change lives. 

Media contact:   

• Julie Ferris-Tillman, Ph.D., Mayo Clinic Communications, newsbureau@mayo.edu  

The post Mayo Clinic AI helps specialists detect pancreatic cancer up to 3 years before diagnosis in landmark validation study appeared first on Mayo Clinic News Network.

Momentum is growing in the fight against amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two devastating neurological diseases now understood to be closely connected. At Mayo Clinic, researchers and clinicians are turning scientific breakthroughs into progress for patients and their families.

Watch: Dr. Bjorn Oskarsson explains work of ALS researchers

Journalists: Broadcast-quality soundbites are available for download at the end of this post. Please courtesy: "Mayo Clinic."

ALS, also known as motor neuron disease and Lou Gehrig's disease, affects nerves, leading to progressive weakness and loss of movement. FTD is a group of brain disorders that affect behavior, personality and language. Although these related conditions usually occur separately, they can occur together and pose significant challenges for patients and families.

While effective treatments remain limited, new approaches are emerging. Patients can receive supportive care to improve quality of life and extend survival, and recent advances include therapies for some genetic forms of ALS. These developments are making diagnostic testing increasingly important to identify potentially treatable causes.

Tools to diagnose ALS

Diagnosis of ALS typically includes a physical exam, medical history and electromyography (EMG), a specialized test of muscles and nerves that detects lower motor neuron degeneration. Mayo Clinic physicians are also using newer tools to improve detection.

"We now have an added blood test, neurofilament light, which is good at detecting ALS," says Bjorn Oskarsson, M.D., a neurologist and director of the ALS Clinic at Mayo Clinic in Florida. "The test measures a nerve protein that leaks into the blood and is significantly elevated in patients with this disease. Another test uses advanced imaging to detect a marker of upper motor neuron degeneration, allowing earlier diagnosis in some patients."

With ultra-high-resolution 7-Tesla MRI imaging, physicians and scientists can identify upper motor neuron degeneration in many people with ALS and help distinguish the disease from similar conditions. These tools, combined with genetic testing, help clinicians make more accurate diagnoses.

Research

Artificial intelligence shows promise in helping patients achieve greater independence. As ALS progresses, patients may lose the ability to speak. Voice-cloning technology recreates a person's voice from a previous recording, helping them continue communicating with loved ones through speaking devices.

This progress builds on a pivotal scientific discovery: In 2011, Mayo Clinic researchers helped discover that ALS and FTD can share a common underlying genetic cause, the C9orf72 mutation. This finding showed that the two conditions are part of a disease spectrum and transformed both research and clinical care. Neurogeneticist Rosa Rademakers, Ph.D., who was on the Mayo Clinic faculty from 2005 to 2019, received the 2026 Breakthrough Prize in Life Sciences for this discovery during her research at Mayo Clinic. She continues to collaborate with colleagues as a supplemental consultant in the Department of Neurosciences at Mayo Clinic.

Mayo Clinic researchers are developing new therapies that target the genetic and biological drivers of ALS and FTD. Clinical trials are underway that focus on treating the underlying disease mechanisms rather than symptoms alone.

Advances in genetic sequencing are providing new insights. Technologies that can read long stretches of DNA are allowing scientists to study the C9orf72 mutation in greater detail. Research led by Marka van Blitterswijk, M.D., Ph.D., a neuroscientist at Mayo Clinic in Florida, shows that variations in the length of this genetic repeat are linked to when symptoms begin, how quickly the disease progresses and the buildup of harmful proteins in the brain.

"It is a very exciting time to investigate ALS and FTD," says Dr. Van Blitterswijk. "New advances in genetic sequencing now enable us to look at the DNA and RNA at unprecedented resolution, creating tantalizing opportunities that will undoubtedly uncover novel causes, as well as much-needed biomarkers and therapeutic strategies for these debilitating diseases in the foreseeable future."

Researchers are also using advanced RNA analysis to better understand how genes function in diseased brain tissue. These findings could lead to earlier diagnosis and new treatments.

Additional research led by Wilfried Rossoll, Ph.D., a Mayo Clinic neuroscientist, is focused on proteins involved in disease progression. In ALS and FTD, a protein called TDP-43 forms clumps within brain cells. This pathology can disrupt essential functions, such as the cell's internal transport system, which can lead to cell damage or death. Mayo Clinic researchers have found that another protein, KPNB1, may help break apart these clumps and restore normal cell function.

Researchers are also working to identify additional genetic factors that influence ALS risk and progression. This work may improve understanding of neurodegenerative diseases and support the development of more precise clinical trials and targeted therapies.

A deeper understanding of ALS and FTD may lead to earlier intervention, more personalized care and improved outcomes for patients and families.

 Related:

• Mayo-clinic-researcher-awarded-breakthrough-prize-for-ALS-dementia-gene-discovery
• Florida dad receives first-in-world ALS treatment
• Mayo Clinic awarded federal grant to study experimental ALS drug
• Mayo researchers, collaborators affirm useful blood biomarker for group of brain disorders in new study

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