JACKSONVILLE, Fla. — Mayo Clinic's pioneering exploration of stem cell-based therapies for bone loss is headed to space. Abba Zubair, M.D., Ph.D., is medical director of Transfusion Medicine and Stem Cell Therapy at Mayo Clinic in Florida.

He is leading research exploring how bone-forming stem cells behave in microgravity in hopes of developing novel treatments for diseases that cause bone loss, including osteoporosis. 

Dr. Zubair's research is one of several science experiments selected by NASA as part of the 33rd SpaceX Commercial Resupply Mission to the International Space Station.

The SpaceX Dragon spacecraft on a Falcon 9 rocket is targeted for 2:45 a.m. EDT, Sunday, Aug. 24, from Cape Canaveral Space Force Station in Florida.

In addition to the science experiments, the Dragon spacecraft will deliver 5,000 pounds of supplies, including food and equipment to the crew at the orbital laboratory.

"For this project, our goal is to really understand how gravity affects bone formation and bone loss, particularly in relation to mesenchymal stem cells and other bone-forming cells," says Dr. Zubair.

"This is going to be significant because it will help us better understand the mechanisms of bone loss during vital times such as in menopausal women or people who are bedridden for extended amounts of time." 

Dr. Zubair believes the research also will provide hope for hundreds of millions of people worldwide affected by osteoporosis, the disease that weakens bones and increases the risk of fractures.

Dr. Zubair's research also is aimed at improving the health of astronauts. Astronauts lose measurable bone density while living in space.

Dr. Zubair's team has identified a protein in the body called IL-6 that can send signals to stem cells to promote bone formation or bone loss. Dr. Zubair's research will investigate whether a new compound can block IL-6 signals and reduce bone loss while in space. 

"If this compound we are testing is able to block the impact of microgravity to slow or stop bone loss, then we can find a treatment for the bone loss in space, and that might also give us a clue into how we may treat people on Earth," says Dr. Zubair.

For more than 20 years, Dr. Zubair has led the Stem Cell Laboratory on Mayo Clinic's Florida campus, developing safe, clinical-grade cell therapy products. His broader research focus aims to harness stem cells to treat degenerative diseases and engineer immune cells to enhance therapeutic outcomes and meet regulatory standards. 

Dr. Zubair's research could potentially advance treatments for brain injury, lung disease, stroke and neurological recovery, cancer, blood stem cell therapies, and epilepsy.

His newest research on bone loss will be his fourth space project selected by NASA at the space station. In recognition of his work, Dr. Zubair received an Exceptional Scientific Achievement Medal from NASA.

From an early age in Nigeria, Dr. Zubair was captivated by space, spending countless hours gazing at the night sky and dreaming of becoming an astronaut. His work as a physician-scientist conducting research in space to improve humanity allows him the best of both worlds.

"I love it. It will be my fourth time attending a launch at the space center. I always get a thrill and wish I was on that rocket heading out," says Dr. Zubair. "It is an unbelievable experience."

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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 contacts:

• Tia Ford, Mayo Clinic Communications, newsbureau@mayo.edu
• Marty Velasco Hames, Mayo Clinic Communications, newsbureau@mayo.edu

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For years, cancer researchers have been trying to halt a type of molecule that's involved in several cancers. The molecules — enzymes known as trypsins — split proteins that help tumors grow and spread.

Mayo Clinic cancer biologist Evette Radisky, Ph.D., previously found that one trypsin, called mesotrypsin, plays a role in breast, prostate, pancreatic and lung cancer. Like other enzymes, the molecule has an active site that kicks off reactions with other molecules. Researchers have tried to block the active site but haven’t found a molecule with a specific enough lock-and-key fit to jam the active region.

Recently, however, Dr. Radisky's lab at Mayo Clinic in Florida discovered a new way to block mesotrypsin. They found a "hidden pocket" in the molecule.

"The hidden pocket is separate from the active site, but we found that blocking it has a similar effect of locking the enzyme in an inactive state," says Dr. Radisky, principal investigator of the study that appeared in Science Advances. The team now is taking steps to discover drugs that fit the hidden pocket.

A mystery in the data

"It was a serendipitous finding," says the study’s lead author, Mathew Coban, of the pocket's discovery. As a research technologist in the Radisky lab and a master's degree student at Mayo Clinic Graduate School of Biomedical Sciences, Coban had aimed to understand the structure of mesotrypsin through X-ray crystallography.

The complex technique, which records scattered X-rays as shadows, can describe the overall folds of amino acids in the enzyme and suggest complementary molecules that fit like a puzzle. While reviewing the X-ray crystallography results, Coban noticed a segment of the enzyme that looked out of place. The research team thought it might be an error in the data and set the results aside.

But Coban continued to wonder about the strange area. He had the idea to begin looking for alternate nooks in the mesotrypsin enzyme that could potentially contribute to a stable, non-active enzyme.

What Coban found was a site that was hidden. The team dubbed it a "cryptic pocket." The pocket, adjacent to the active site, opened at moments when mesotrypsin stabilized itself. The next step was clear. "If the pocket is there some of the time, maybe a drug would be able to bind at that site and trap the enzyme in its inactive state," he says.

Finding a drug that binds

The team worked with a colleague, Thomas Caulfield, Ph.D., a former Mayo researcher and drug discovery expert, to conduct a computational screen of potential drug compounds that might fit in the cryptic pocket. They found a single molecule that could bind in the cryptic pocket and inhibit the activity of mesotrypsin.

Importantly, the researchers note, the molecule blocks mesotrypsin selectively, without affecting other trypsins. This could mean less toxicity or fewer side effects for a patient. The finding also means that other cryptic pockets may exist in other trypsin molecules related to cancer, presenting new potential drug targets.  

The team is continuing to look for drug molecules that fit mesotrypsin even better. "Based on the structural information of mesotrypsin that we have now, we've been able to do more computational prediction to identify additional, more potent compounds that we’re now testing in the laboratory," says Dr. Radisky.

"This has been an important step in the understanding of this key enzyme. Our next steps will be to start testing how well our candidate drug molecules fit the cryptic pocket and block cancer invasion and metastasis in models of disease," she says.

The study was funded by grants from the National Institutes of Health, Mayo Clinic Medical Scientist Training Program and Department of Energy Office of Science User Facility.  The authors declare that they have no competing interests.

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While doctors are often focused on monitoring the health and vital signs of others, a new study had some tuning in to their own health and vital statistics as well. The results suggest that doing so may offer doctors real benefits to their own well-being, in a scalable way. 

Physicians who wore a smartwatch and had access to their personal health data — including information on their heart rate, sleep, breathing patterns and physical activity — reported greater resilience and 54% saw a reduction in the overall odds of burnout compared to those who did not receive a study smartwatch, according to new research published in JAMA Network Open. Mayo Clinic investigators conducted the study in collaboration with the University of Colorado School of Medicine.

"Advancing care starts with caring for those who deliver it. We're shaping a future where the well-being of our workforce is integral to the care we deliver."   - Colin West, M.D., Ph.D., Medical Director of Employee Well-Being at Mayo Clinic

Physician well-being is essential not only to personal health, but also to the quality of care patients receive. It's tied to job performance, patient safety, access to care and workforce sustainability.  

That’s why Mayo Clinic and others are prioritizing strategies to strengthen and sustain the well-being of healthcare professionals. 

How the smartwatch trial was designed and conducted 

The 12-month trial was conducted at Mayo Clinic and the University of Colorado School of Medicine. It included 184 physicians across specialties such as primary care, surgery, neurology and oncology. Researchers randomly assigned about half of the participants to wear a smartwatch for the full 12 months, while they gave the other half the watch during the study’s second half.

All participants received brief newsletters with general tips on smartwatch use and reminders to sync their devices. These resources aimed to support awareness of the tools and encourage engagement with personal health data.

Physicians in both study groups wore the device more than 70% of the time during the trial. Participants also completed validated well-being surveys at the beginning and end of the study. 

Participants could view their health data through a mobile app but were not prompted to take specific actions in response to it. Researchers say even this passive approach may help support well-being.  

Designing smarter tools for a healthy workforce

The study was co-designed and led by Arjun Athreya, Ph.D., an electrical and computer engineer in Mayo Clinic's Department of Molecular Pharmacology and Experimental Therapeutics; Colin West, M.D., Ph.D., medical director of Employee Well-Being at Mayo Clinic; and study Principal Investigator Liselotte Dyrbye, M.D., M.H.P.E., senior associate dean for faculty and chief well-being officer at the University of Colorado School of Medicine.  

"We're entering an era where wearable technology, when paired with thoughtful design and artificial intelligence methods that use the data, could help personalize well-being strategies in clinical settings," Dr. Athreya says. "This study shows we can support healthcare professionals with passive monitoring digital technologies with innovative engagement strategies to provide potentially helpful data without adding burden to their day."  

The researchers say this approach can offer timely support as part of a broader physician well-being strategy. 

"While this is an individually focused intervention, it offers an evidence-based way to support physicians in the short term, complementing longer-term efforts aimed at addressing systemic contributors to physician stress," says Dr. Dyrbye. 

Caring for caregivers: A vision for the future

Next steps for the researchers include evaluating long-term outcomes of the smartwatch project. They also plan to explore whether this approach can support other healthcare professionals.

"Advancing care starts with caring for those who deliver it," says Dr. West. "We’re shaping a future where the well-being of our workforce is integral to the care we deliver."   

The Physicians Foundation, Mayo Clinic's Center for Individualized Medicine, and the University of Colorado School of Medicine partly funded the study. Review the study for a complete list of authors, disclosures and funding details. 

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ROCHESTER, Minn. — The immune system is meant to protect the body from infection and disease. But with age, it can become less capable of doing so. However, Mayo Clinic researchers have found that some older people maintain "immune youth" – a new term coined by Mayo researchers to explain a young immune system in someone over age 60.

"We are studying why some individuals have a 'fountain of youth' in their immune systems. We want to learn from them," says Cornelia Weyand, M.D., Ph.D., a Mayo Clinic rheumatologist and clinician-scientist. She is a lead author on a perspective paper published in Nature Aging.

Dr. Weyand's research team discovered this cellular fountain of youth in more than 100 older patients who came to Mayo Clinic to receive treatment for an autoimmune disease that affects the arteries, including the aorta, called giant cell arteritis. Dr. Weyand and colleagues found in the diseased tissue of these patients specialized immune cells, called stem-like T cells. These immune cells behave like young stem cells that usually regenerate and aid healing and growth; but in this case, they were spreading the disease. This team of researchers also discovered autoimmune stem cells in humans previously.

"We observed that these patients have very young immune systems despite being in their 60s and 70s. But the price they pay for that is autoimmunity," she says.

Autoimmunity is when the immune system mistakenly attacks healthy tissues and organs.

In addition, the researchers saw that the immune checkpoint inhibitors that regulate the immune system were not working properly.

Benefits of immune system aging

"Contrary to what one may think, there are benefits to having an immune system that ages in tandem with the body," says Jörg Goronzy, M.D., Ph.D., a Mayo Clinic researcher on aging who is a co-lead author of the paper. "We need to consider the price to pay for immune youthfulness. That price can be autoimmune disease."

Immune aging is a sophisticated adaptation mechanism that the immune system can use to prevent autoimmune disease, say the researchers.

They are in the process of developing new diagnostic tests that will help find patients and healthy individuals who carry high numbers of immune stem cells and may be predisposed to autoimmune disease later in life. The research is part of a larger effort at Mayo Clinic called the Precure initiative, focused on developing tools that empower clinicians to predict and intercept biological processes before they evolve into disease or progress into complex, hard-to-treat conditions.

Review the study for a complete list of authors, disclosures and funding. 

Additional resources:
Mayo Clinic advances research on mysterious blood vessel disease

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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:

• Alison Satake, Mayo Clinic Communications, newsbureau@mayo.edu

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Changes in how brain cells generate energy may drive the development of Alzheimer's disease and influence how patients respond to therapy, according to a new study from Mayo Clinic researchers. The findings, published in the journal Alzheimer's & Dementia, spotlight mitochondrial complex I — a critical component of cellular energy production — as both a contributor to disease progression and a promising target for new treatments.

Led by senior author Eugenia Trushina, Ph.D., the Mayo Clinic team found that disruptions in complex I activity can trigger gene expression patterns commonly observed in Alzheimer's disease. The researchers demonstrated that using small molecules to gently adjust how complex I functions can help activate protective mechanisms in brain cells.

"This research offers new clues about how Alzheimer’s begins and shows a promising new path for developing better, more personalized treatments," says Dr. Trushina, a researcher who studies neurodegenerative diseases.

Mitochondria, often described as the powerhouse of the cell, produces the energy necessary for proper cellular function. In neurons, which have especially high energy demands, mitochondrial dysfunction can have devastating consequences. The Mayo Clinic researchers found that when complex I is not working properly, it disrupts how brain cells manage energy and respond to stress — changes that resemble those seen in the brains of people with Alzheimer's disease.

Using experimental models and advanced molecular and computational tools, the team showed that mild modulation of complex I activity with specially designed small molecules helped neurons launch protective responses, such as reducing inflammation and improving energy balance.

Interestingly, they found that males and females responded differently to these treatments, suggesting a need for sex-specific approaches to therapy. "This sex-dependent effect is intriguing," says Dr. Trushina. "It suggests that future therapies could be tailored by sex, especially for a disease like Alzheimer's that affects men and women differently."

Current Alzheimer's treatments mostly focus on managing symptoms or targeting hallmark brain changes such as amyloid plaques and tau tangles. However, these approaches have seen limited success in halting disease progression. The new study points to mitochondrial dysfunction as a possible upstream trigger — one that may begin long before cognitive symptoms emerge.

"This study gives us a deeper understanding of the cellular events that spark Alzheimer's and, more importantly, how we might intervene to slow or prevent its progression," says Dr. Trushina. "Our results open the door to a new class of drugs that work by protecting the brain's energy supply and buffering it against early disease-related changes."

The research is part of a larger effort at Mayo Clinic called the Precure initiative, focused on developing tools that empower clinicians to predict and intercept biological processes before they evolve into disease or progress into complex, hard-to-treat conditions. In the future, the team plans to further investigate the safety and effectiveness of complex I modulators in preclinical models, with the goal of advancing into clinical trials.

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ROCHESTER, Minn. — Scientific breakthroughs in one disease don't always shed light on treating other diseases. But that's been the surprising journey of one Mayo Clinic research team. After identifying a sugar molecule that cancer cells use on their surfaces to hide from the immune system, the researchers have found the same molecule may eventually help in the treatment of type 1 diabetes, once known as juvenile diabetes.

Type 1 diabetes is a chronic autoimmune condition in which the immune system errantly attacks pancreatic beta cells that produce insulin. The disease is caused by genetic and other factors and affects an estimated 1.3 million people in the U.S.

In their studies, the Mayo Clinic researchers took a cancer mechanism and turned it on its head. Cancer cells use a variety of methods to evade immune response, including coating themselves in a sugar molecule known as sialic acid. The researchers found in a preclinical model of type 1 diabetes that it's possible to dress up beta cells with the same sugar molecule, enabling the immune system to tolerate the cells.

"Our findings show that it's possible to engineer beta cells that do not prompt an immune response," says immunology researcher Virginia Shapiro, Ph.D., principal investigator of the study, published in the Journal of Clinical Investigation.

A few years ago, Dr. Shapiro's team demonstrated that an enzyme, known as ST8Sia6, that increases sialic acid on the surface of tumor cells helps tumor cells appear as though they are not foreign entities to be targeted by the immune system.  

"The expression of this enzyme basically ‘sugar coats' cancer cells and can help protect an abnormal cell from a normal immune response. We wondered if the same enzyme might also protect a normal cell from an abnormal immune response," Dr. Shapiro says. The team first established proof of concept in an artificially-induced model of diabetes.

In the current study, the team looked at preclinical models that are known for the spontaneous development of autoimmune (type 1) diabetes, most closely approximating the process that occurs in patients. Researchers engineered beta cells in the models to produce the ST8Sia6 enzyme.

In the preclinical models, the team found that the engineered cells were 90% effective in preventing the development of type 1 diabetes. The beta cells that are typically destroyed by the immune system in type 1 diabetes were preserved.

Importantly, the researchers also found the immune response to the engineered cells appears to be highly specific, says M.D.-Ph.D. student Justin Choe, first author of the publication. Choe conducted the study in the Ph.D. component of his dual degree at Mayo Clinic Graduate School of Biomedical Sciences and Mayo Clinic Alix School of Medicine.

"Though the beta cells were spared, the immune system remained intact," Choe says. The researchers were able to see active B- and T-cells and evidence of an autoimmune response against another disease process. "We found that the enzyme specifically generated tolerance against autoimmune rejection of the beta cell, providing local and quite specific protection against type 1 diabetes."

No cure currently exists for type 1 diabetes, and treatment involves using synthetic insulin to regulate blood sugar, or, for some people, undergoing a transplant of pancreatic islet cells, which include the much-needed beta cells. Because transplantation involves immunosuppression of the entire immune system, Dr. Shapiro aims to explore using the engineered beta cells in transplantable islet cells with the goal of ultimately improving therapy for patients.

"A goal would be to provide transplantable cells without the need for immunosuppression," says Dr. Shapiro. "Though we're still in the early stages, this study may be one step toward improving care."

The research was funded by grants from the National Institutes of Health.

Please see the study for the full list of authors.

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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

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Researchers are leading the nation in using powerful and precise radioactive drugs to treat people with complex cancers.  

ROCHESTER, Minn. — Mayo Clinic has treated the first person in the U.S. using a novel radioactive medicine for advanced breast cancer as part of an international multisite clinical trial.

The medicine used in this clinical trial contains actinium-225, a highly potent alpha-emitting radiopharmaceutical therapy that was first developed for a subtype of gastroenteropancreatic neuroendocrine tumors, which are rare and can form in the pancreas and the gastrointestinal tract. The alpha-emitting radiopharmaceutical therapy is intended to work by passing through the blood to stick to cancer cells, delivering powerful and precise radiation without harming healthy cells.

The Mayo Clinic researchers are the first to apply this therapy in America to a patient with metastatic breast cancer. The phase 1b/2 open-label trial is being conducted at all three academic Mayo Clinic sites in Rochester, Minnesota; Phoenix; Jacksonville, Florida; and approximately 20 other sites across the U.S. The first person treated was at Mayo Clinic in Florida.

The principal investigator at Mayo Clinic is Geoffrey Johnson, M.D., Ph.D., a professor of radiology and a leader in radiopharmaceutical therapies. He says these are innovative cancer treatments that use radioactive medicines designed to target and kill cancer cells with high precision.

Mayo Clinic has nearly 20 active radiopharmaceutical therapy clinical trials, with 10 more preparing to launch, targeting many different types of cancer. Mayo Clinic in Rochester treats more patients with modern radiopharmaceutical therapies, such as lutetium dotatate for neuroendocrine cancers and lutetium PSMA for prostate cancers, than any other center in the world.

Lutetium dotatate and lutetium PSMA are beta-emitting radiopharmaceuticals. They use beta particles, which are tiny subatomic particles, to radiate at a low level. In contrast, alpha-emitting radiopharmaceuticals use alpha particles that are 8,000 times more massive than beta particles, and travel only three cell diameters after they are emitted from the therapy.

"This means alpha emitters can deliver a much more powerful impact over a shorter distance. If you consider killing a cancer cell is like knocking down a brick wall, then the difference is like throwing a 10-pound dumbbell (beta) at the wall versus a fully loaded Mack truck (alpha)," says Dr. Johnson. "The alpha emitter's potential lies in its power and in its ability to precisely kill even a single cancer cell without injuring surrounding healthy tissue, making it a next-generation therapy."

In preclinical studies, data indicates actinium-225 DOTATATE that targets the somatostatin receptor subtype 2expression demonstrated feasibility and potential efficacy for treatment of ER+ metastatic breast cancer in the laboratory. The drug was developed by RayzeBio Inc., a Bristol Myers Squibb Company, the sponsor of the active phase 1b/2 clinical trial.

Study Title: Phase 1b/2 Open-label Trial of 225Ac-DOTATATE (RYZ101) in Subjects with Estrogen Receptor-positive (ER+), Human Epidermal Growth Factor Receptor 2 (HER2)-negative, Locally Advanced and Unresectable or Metastatic Breast Cancer Expressing Somatostatin Receptors (SSTRs) and Progressed After Antibody-drug Conjugates And/or Chemotherapy (TRACY-1)

• Descriptor: Phase 1b/2 open-label trial of 225Ac-DOTATATE (RYZ101) alone and with pembrolizumab in subjects with ER+, HER2-negative unresectable or metastatic breast cancer expressing SSTRs.
• Sponsor: RayzeBio Inc.
• Link: https://clinicaltrials.gov/study/NCT06590857

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

Media contact:

• Brittany Cordeiro, Mayo Clinic Communications, newsbureau@mayo.edu

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(Video animation shows blood stem cells dividing and multiplying. Getty Images).

Deep inside the body, a slow-growing cluster of mutated blood cells can form. This cluster, found in 1 in 5 older adults, can raise the risk of leukemia and heart disease, often without warning. 

To better understand this hidden risk, Mayo Clinic researchers have developed an artificial intelligence (AI) tool to help investigators uncover how it contributes to disease risk and progression.

In a study published in Genomics, Proteomics & Bioinformatics, the tool showed promising results in identifying early signs of this condition, known as clonal hematopoiesis of indeterminate potential, or CHIP.

When blood cells mutate

CHIP starts in the bone marrow, where blood stem cells make the cells that keep organs working, oxygen flowing and the immune system strong. But if one of those cells acquires a mutation in a gene linked to blood cancer, it can multiply abnormally, forming a cluster of mutated cells that gradually expands. 

This can cause CHIP, a condition with no symptoms that researchers link to higher rates of death, especially from heart disease. Because its effects vary, CHIP is hard to track and often goes undetected for years. 

CHIP makes leukemia more than 10 times more likely and raises the risk of heart disease up to four times, even in healthy adults. Finding it earlier could help guide proactive monitoring or preventive care.

A new tool for early detection 

The new tool, called UNISOM — short for UNIfied SOmatic calling and Machine learning — was developed by Shulan Tian, Ph.D., under the leadership of Eric Klee, Ph.D., co-senior author of the study and the Everett J. and Jane M. Hauck Midwest Associate Director of Research and Innovation.  

UNISOM helps clinicians identify CHIP-related mutations in standard genetic datasets, opening new avenues for research and discovery. In the past, that level of detection required more complex and advanced sequencing methods. 

"Detecting disease at its earliest molecular roots is one of the most meaningful advances we can make in medicine," says Dr. Klee. "UNISOM is just one of many examples of how we're translating genomic science into innovative tools that support timely and informed care." 

UNISOM helped researchers detect nearly 80% of CHIP mutations using whole-exome sequencing, which analyzes the protein-coding regions of DNA.  

The team also tested UNISOM on whole-genome sequencing data from the Mayo Clinic Biobank, which captures nearly all of a person's genetic code. In that data, it detected early signs of CHIP, including mutations present in fewer than 5% of blood cells. Standard techniques often miss these small but important changes.

"We're engineering a path from genomic discovery to clinical decision-making," says Dr. Tian, the co-senior author and a bioinformatician at Mayo Clinic. "It's rewarding to help bring these discoveries closer to clinical care, where they can inform decisions and support more precise treatment." 

Next, the team plans to apply UNISOM to larger and more diverse datasets to support research and expand its use in clinical practice. 

Review the study for a complete list of authors, disclosures and funding.   

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For nearly three decades, Mayo Clinic researcher Christopher Evans, Ph.D., has pushed to expand gene therapy beyond its original scope of fixing rare, single-gene defects. That has meant systematically advancing the field through laboratory experiments, pre-clinical studies and clinical trials.

Several gene therapies have already received approval from the U.S. Food and Drug Administration (FDA), and experts predict that 40 to 60 more could be approved over the next decade for a range of conditions. Dr. Evans hopes a gene therapy for osteoarthritis — a form of arthritis affecting more than 32.5 million U.S. adults — will be one of them.

Recently, Dr. Evans and a team of 18 researchers and clinicians reported the results of a first-in-human, phase 1 clinical trial of a novel gene therapy for osteoarthritis. The findings, published in Science Translational Advances, demonstrated that the therapy is safe, achieved sustained expression of a therapeutic gene inside the joint and offered early evidence of clinical benefit.

"This could revolutionize the treatment of osteoarthritis," says Dr. Evans, who directs the Musculoskeletal Gene Therapy Research lab at Mayo Clinic.

In osteoarthritis, the cartilage that cushions the ends of bones — and sometimes the underlying bone itself — degenerates over time. It is a leading cause of disability, and notoriously difficult to treat. "Any medications you inject into the affected joint will seep right back out in a few hours," says Dr. Evans. "As far as I know, gene therapy is the only reasonable way to overcome this pharmacologic barrier, and it's a huge barrier." By genetically modifying cells in the joint to produce their own pharmacy of anti-inflammatory molecules, Evans aims to engineer knees that are more resistant to arthritis.

The Evans laboratory found that a molecule called interleukin-1 (IL-1) plays an important role in fueling inflammation, pain and cartilage loss in osteoarthritis. As luck would have it, the molecule had a natural inhibitor, aptly named the IL-1 receptor antagonist (IL-1Ra), that could form the basis of the first gene therapy for the disease. In 2000, Dr. Evans and his team packaged the IL-1Ra gene into a harmless virus called AAV, which they tested in cells and then pre-clinical models. The results were encouraging.

In pre-clinical testing, his collaborators at the University of Florida demonstrated that the gene therapy successfully infiltrated the cells that make up the synovial lining of the joint as well as the neighboring cartilage. The therapy protected the cartilage from breakdown. In 2015, the team got investigational new drug approval to start human testing. But regulatory hurdles and manufacturing challenges kept them from injecting their first patient for another four years. Mayo Clinic has since established a new process for accelerating clinical trial activation that could help researchers launch studies more quickly.

In the recent study, Dr. Evans and his team gave the experimental gene therapy to nine patients with osteoarthritis, delivering it directly into the knee joint. They found that the levels of the anti-inflammatory IL-1Ra increased and remained elevated in the joint for at least a year. Participants also reported reduced pain and improved joint function, with no serious safety issues. Dr. Evans says the findings suggest the treatment is safe and may offer long-lasting relief from osteoarthritis symptoms. "This study provides a highly promising, novel way to attack the disease," he says.

Dr. Evans has co-founded an arthritis gene therapy company called Genascence to drive the project forward. The company just completed a larger phase Ib study and is in discussions with the FDA about launching a pivotal phase IIb/III clinical trial to evaluate the therapy's effectiveness, the next step before FDA approval for the therapy.

Review the study for a complete list of authors, disclosures and funding. 

Additional resources:

• Pushing the limits of gene therapy for osteoarthritis

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ROCHESTER, Minn. — Mayo Clinic took a pivotal step toward integrating AI solutions in the clinical setting with the deployment of NVIDIA DGX SuperPOD with NVIDIA DGX B200 systems, an advanced infrastructure that provides state-of-the-art AI compute capabilities.

Mayo Clinic and NVIDIA collaborated to enable the rapid innovation and development of foundation models in support of Mayo’s platform approach to healthcare, contributing to Mayo Clinic’s Bold. Forward. strategy and new innovations for generative AI solutions and digital pathology. These innovations are delivering new insights as Mayo is driving to improve patient outcomes and transform healthcare.

"Our aspiration for AI is to meaningfully improve patient outcomes by detecting disease early enough to intervene. What was once a hypothetical — 'If only we had the right data' — is now becoming reality thanks to AI and advanced computing," says Matthew Callstrom, M.D., Ph.D., medical director of the Department of Strategy and leader of Mayo Clinic’s Generative Artificial Intelligence Program.

The advanced computing infrastructure will initially support foundation model development for pathomics, drug discovery and precision medicine.

The NVIDIA Blackwell-powered DGX SuperPOD is built to efficiently process large, high-resolution imaging essential for AI foundation model training. Designed for speed and scalability, the Blackwell infrastructure enables Mayo Clinic to accelerate pathology slide analysis and foundation model development — reducing four weeks of work to just one, ultimately improving patient outcomes. This advanced computing infrastructure will also advance Mayo Clinic’s generative AI and multimodal digital pathology foundation model development.

Mayo Clinic, in partnership with Aignostics, developed a leading pathology foundation model called Atlas, trained on more than 1.2 million histopathology whole-slide images. With Atlas, Mayo Clinic clinicians and researchers can improve accuracy and reduce administrative tasks. The new computing capabilities will accelerate and improve clinical model development.

"This compute power, coupled with Mayo’s unparalleled clinical expertise and platform data of over 20 million digitized pathology slides, will allow Mayo to build on its existing foundation models. We’re transforming healthcare by quickly and safely developing innovative AI solutions that can improve patient outcomes and enable clinicians to dedicate more time to patient care while also accelerating commercial affiliations with other industry leaders," says Jim Rogers, CEO of Mayo Clinic Digital Pathology.

Journalists: Media kit with images for download available here.

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About Mayo Clinic Digital Pathology
Mayo Clinic Digital Pathology facilitates the global scaling of digital pathology solutions to benefit clinicians and patients, advancing key areas such as scanning, storage, foundation model development and the creation and deployment of cutting-edge algorithms. Working with Mayo Clinic innovators and external collaborators, Mayo Clinic Digital Pathology is wholly owned by Mayo Clinic and seeks to incubate and start impactful companies while investing in and acquiring existing companies, spurring innovation across pathology.

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:

• Terri Malloy, Mayo Clinic Communications, newsbureau@mayo.edu

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