José Villalta prided himself on providing for his wife and son, first by working construction jobs and then by canning vegetables at Faribault Foods. He was known for being strong and capable, with dark eyes and an easy smile. But in his early 40s that changed, and quickly. "I don't feel the same," he told his wife, Sylvie. His muscles, once one of his defining features, grew progressively weaker. He had trouble walking. Within months, he had to use a cane, then a wheelchair, to get around.

Doctors told him to take more vitamins. They tried acupuncture and electroshock therapy. A specialist biopsied a piece of his leg muscle but could not determine the cause of his deteriorating health. By the time he made his way to Mayo Clinic, he could no longer muster the strength to lift his arms or even hold up his head. "He was like a puppet," says Sylvie.

Ashley Santilli, M.D., the clinical fellow at Mayo Clinic assigned to his case, told the family not to lose hope. "She was really persistent," recalls Sylvie. "She said 'We will get to the bottom of this — we will figure out what's wrong.'"

Integrated know-how

At the time, Dr. Santilli was training under Teerin Liewluck, M.D., a neurologist who had trained under the late Andrew Engel, M.D., a pioneer of muscle disease research. Over nearly six decades at Mayo Clinic, Dr. Engel discovered several new neuromuscular disorders and identified the underlying mechanisms of many others.

"One thing he always told me was that he was still learning, even after all those years," says Dr. Liewluck. "He taught me that I need to keep an open mind, because there's always new things to learn and discover."

Because Villalta's mysterious illness arose rapidly and later in life, Dr. Liewluck thought the cause was probably not genetic. Congenital muscle diseases typically emerge slowly in early childhood. But when he looked at Villalta's muscle biopsy under the microscope, he was surprised to see abnormally large mitochondria, the energy-producing structures often called the "powerhouses of the cell." Giant mitochondria (also known as megaconia) are associated with a type of congenital muscular dystrophy caused by mutations in a gene called CHKB.

To make sure they were not missing a new presentation of this incurable condition, the team requested genetic testing, which confirmed that Villalta did not harbor any suspicious CHKB variants. So they returned to the biopsy in search of more clues.

"The unique thing about neuromuscular medicine at Mayo is we get specific training in diagnostic tests, like biopsy interpretation and EMG," says Dr. Santilli, referring to electromyography, a test that measures muscle response to nerve stimulation. "You get to be the whole provider for a particular patient, instead of relying on other specialists to help us interpret those tests."

A new disease

Villalta's case gave Dr. Liewluck a sense of déjà vu. He recalled another patient, years earlier, who was part of a study on a severe form of muscle inflammation. That patient's biopsy also was marked by giant mitochondria. The patient's story was only pieced together later: an adult who developed muscle weakness, but whose illness was complicated by an underlying cancer. Treated by another physician, the patient initially improved with immunotherapy, but ultimately the cancer claimed her life.

To better understand Villalta's muscle disease, the researchers performed a series of special stains on his biopsy, each revealing various aspects of muscle structure and pathology. In addition to the unusually large mitochondria within his muscle fibers, they found evidence of inflammation, indicating an autoimmune process was at play. The team believed that Villalta's immune system was mistakenly attacking his muscles. If they were right, then immunotherapy might help him regain his strength.

"We couldn't guarantee or predict the outcome," says Dr. Liewluck.

They told Villalta that he would be the first patient they treated with this new disease, which they called immune-mediated megaconial myopathy (IMMM). They treated him aggressively with regular rounds of intravenous immunoglobulin and steroids. And he got better.

Before treatment, Villalta's levels of creatine kinase, a blood biomarker commonly used to monitor muscle damage, were sky high. With treatment, those levels dropped back within the normal range, suggesting that his overactive immune system had been put in check. More importantly, Villalta felt stronger and required less assistance, showering on his own, tinkering in his garage — even driving himself to rehab.

Unfortunately, Villalta's illness may have gone too long without treatment to allow a full recovery. Chronic inflammation and repeated muscle damage can gradually lead to the replacement of healthy muscle tissue with fat and scar tissue.

"That gives you evidence that you need to catch these cases earlier," says Dr. Liewluck.

Earlier answers

The team turned to the Mayo Clinic Muscle Pathology database to see if they could find other patients with this new disease within recent years. They identified two more patients, who shared the same distinctive features — profound muscle weakness in adulthood, strikingly enlarged mitochondria, inflammatory reaction in muscle tissue and elevated creatine kinase levels. Working in collaboration with an outside institute, they uncovered a third case. Along with Villalta and the case from the prior research study, the count had risen to five. Villalta and the two newer patients, all of whom received immunotherapy, responded well to treatment.

Now, Dr. Liewluck is delving deep into Mayo Clinic's extensive muscle tissue repository, combing through biopsies that span not just recent years, but decades, in search of other overlooked cases — patients who may have had IMMM long before it was recognized as a distinct entity.

"I actually think there might be many more than we know," says Dr. Santilli.

Interestingly, all the patients they have identified thus far have also had some form of pancreatic disease, such as pancreatic cancer or pancreatitis. Though the link is not entirely clear, the pancreas expresses high levels of choline kinase beta, the same protein that is disrupted in CHKB-related muscular dystrophy. Dr. Liewluck is collaborating with neuroimmunologist Div Dubey, M.B.B.S., to try to identify the antibody that triggers the immune attack, ultimately causing disease.

Once they find that autoantibody, they can test for it in the blood to diagnose more patients with IMMM. For now, they will have to rely on their expert review of muscle biopsies combined with clinical observations.

Though Villalta is not back to his old self, he is happy that his case has already helped others. And he is making the most of the strength he has.

By last spring, Villalta had recovered enough to travel to his home country of El Salvador. His family helped him take a walk on the beach and watched over him as he swam in the ocean. Until recently, it was more than he thought was possible.

The post Construction worker rapidly loses ability to walk – Mayo Clinic researchers discover the cause appeared first on Mayo Clinic News Network.

JACKSONVILLE, Fla. — Pick's disease, a neurodegenerative disease of unknown genetic origin, is a rare type of frontotemporal dementia that affects people under the age of 65. The condition causes changes in personality, behavior and sometimes language impairment. In patients with the disease, tau proteins build up and form abnormal clumps called Pick bodies, which restrict nutrients to the brain and cause neurodegeneration. The only way to diagnose the disease is by looking at brain tissue under a microscope after a person dies.

In a new study, Mayo Clinic researchers have identified gene expression changes in the brains of people with Pick's disease. Since Pick's disease is a rare neurodegenerative disorder that cannot be diagnosed during life, their findings offer valuable insights that may help guide the development of biomarkers and therapeutic strategies.

Researchers at Mayo Clinic in Florida, University College London in England and collaborators worldwide have established the Pick's Disease International Consortium to study a specific MAPT gene variation known as MAPT H2 that makes the tau protein and acts as a driver of disease. They investigated a connection between the gene and disease risk, age at onset, and duration of Pick's disease. Their findings are reported in The Lancet Neurology.

Mayo Clinic researchers identified the first MAPT gene mutations for a behavioral form of dementia in 1998, and other genetic changes associated with related dementias in 2001, which paved the way to understanding the mechanisms of tau-related disease. This new study confirms a tau genetic factor linked specifically to Pick's disease and opens up new avenues of therapeutic design.

"Our research could have profound implications for the development of therapies for Pick's disease and other related neurodegenerative diseases, including Alzheimer's disease and progressive supranuclear palsy," says Owen Ross, Ph.D., a Mayo Clinic neuroscientist and senior author of the paper. The consortium hosts a database of clinical, pathological and demographic information about patients with the disease who donated their brain tissue for science.

To conduct the study, researchers investigated brain samples of 338 patients confirmed to have Pick's disease to compare with blood samples from 1,312 neurologically healthy individuals. Patients confirmed to have the disease came from 35 brain banks and hospitals in North America, Europe and Australia between 2020 and 2023. The Mayo Clinic Brain Bank was among the sites in the study that provided the largest collection of samples.

Analyzing DNA from the blood samples and brain tissue, the research team recorded baseline information on study participants, including age at disease onset, age at death for those with Pick's disease, and sex and age at blood collection for the control group. Disease duration was calculated by the difference between age at Pick's disease onset and age at death. In addition, the researchers looked at clinical characteristics such as clinical diagnosis, impairment in behavior and language.

"We found that the MAPT H2 genetic variant is associated with an increased risk of Pick's disease in people of European descent," says Dr. Ross. "We were only able to determine that because of the global consortium, which greatly increased the sample size of pathology cases to study with Pick's disease."

The team's next steps are to expand the consortium to the Middle East, Asia, Africa and Latin America, further resolve the genetic architecture of the disease, and assess this specific genetic variant as a biomarker or test for clinical diagnosis of Pick's disease. There is currently no clinical test or diagnosis available for Pick's disease. For the first time, the creation of the consortium may allow for the development of a clinical test.

Funding for this research at Mayo Clinic was supported in part by the National Institutes of Health, the National Institute of Neurological Disorders and Stroke, the State of Florida Ed and Ethel Moore Alzheimer’s Disease Research Program, and Mayo Clinic Alzheimer's Disease Research Center. For a full list of authors, collaborating institutions and disclosures, see the paper.

###

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: 

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

The post Advancing the study of Pick’s disease, rare form of early-onset dementia appeared first on Mayo Clinic News Network.

Editor's note: May is National Cancer Research Month, and May 20 is Clinical Trials Day.

A cancer diagnosis is an emotional experience. Learning that you have cancer can create feelings of hopelessness, fear and sadness. This is especially true if your cancer is advanced or available treatments are unable to stop or slow its growth.

"Often, when patients are diagnosed with cancer, they feel hopeless and scared. Clinical trials are one way patients can be proactive. They can make a choice in how their care is going to be," says Matthew Block, M.D., Ph.D., a Mayo Clinic medical oncologist.

Cancer clinical trials help physician-scientists test new and better ways to control and treat cancer. During a clinical trial, participants receive specific interventions, and researchers determine if those interventions are safe and effective. Interventions studied in clinical trials might be new cancer drugs or new combinations of drugs, new medical procedures, new surgical techniques or devices, new ways to use existing treatments, and lifestyle or behavior changes.

Clinical trials provide access to potential treatments under investigation, giving options to people who otherwise may face limited choices. "Clinical trials open the door to a new hope that maybe we can fight their cancer back and give them a better quality of life," says Geoffrey Johnson, M.D., Ph.D., a Mayo Clinic radiologist, nuclear medicine specialist and co-chair of the Mayo Clinic Comprehensive Cancer Center Experimental and Novel Therapeutics Disease Group.

You will receive cancer treatment if you participate in a clinical trial. "I think one common misperception about clinical trials is that if you enter a clinical trial, you may not get treatment (receive a placebo). And that's actually very much not true. Most clinical trials are looking at one treatment compared to another treatment," says Judy C. Boughey, M.D., a Mayo Clinic surgical oncologist, chair of Breast and Melanoma Surgical Oncology at Mayo Clinic in Rochester, Minnesota, and chair of the Mayo Clinic Comprehensive Cancer Center Breast Cancer Disease Group.

"I think one common misperception about clinical trials is that if you enter a clinical trial, you may not get treatment (receive a placebo). And that's actually very much not true. Most clinical trials are looking at one treatment compared to another treatment."Judy C. Boughey, M.D.

Watch this video to hear the experiences of people who have participated in cancer clinical trials and to hear Drs. Block, Johnson and Boughey discuss the importance of clinical trials in cancer care:

Clinical trials are a significant part of cancer care at Mayo Clinic Comprehensive Cancer Center. Cancer care teams work together across specialties to make sure the right clinical trials are available to serve the needs of people with cancer who come to Mayo Clinic.

"We are very particular in how we select the clinical trials that we have available for patients," says Dr. Boughey. "We want to have the best trials available for our patients. Some of the clinical trials are evaluating drugs — we are so excited about those drugs, but we can't prescribe those drugs for patients without having that trial. And so we will actually fight to try to get that trial open here to have it available as an opportunity for our patients."

If you choose to participate in a clinical trial, you will continue to receive cancer care. "For most patients that we evaluate, there's always the standard of care treatment option for those patients. And then, in many situations, there's also a clinical trial that the patient can participate in," says Dr. Boughey.

People who participate in clinical trials help make new and better cancer care available for future patients. The treatments available for cancer patients today exist because of the clinical trial participants of yesterday. "We couldn't advance medicine if it wasn't for people volunteering for trials. And the promise from our side is to say we're not going to put patients on trials or offer trials for them to consider unless we think there's a good chance that they'll get a benefit or that society at large will get a benefit," says Dr. Johnson.

"We couldn't advance medicine if it wasn't for people volunteering for trials. And the promise from our side is to say we're not going to put patients on trials or offer trials for them to consider unless we think there's a good chance that they'll get a benefit or that society at large will get a benefit."Geoffrey Johnson, M.D., Ph.D.

Participating in a clinical trial may give you access to cutting-edge treatment, improve your quality of life and extend your time with loved ones.

"It's definitely worth reaching out to your healthcare provider and asking, 'What clinical trials could I be a potential candidate for?'" says Dr. Boughey. "And remember, you can ask this of your surgical oncologist, your medical oncologist, your radiation oncologist, or any of the physicians you're seeing because there are trials in all disciplines. There are also ongoing trials that require the collection of tissue or the donation of blood. They can also be important in trying to help future generations as we continue to work to end cancer."

Participating in a clinical trial is an important decision with potential risks and benefits. Explore these FAQ about cancer clinical trials, and ask your care team if a clinical trial might be right for you.

This article first published on the Mayo Clinic Comprehensive Cancer Center blog.

The post Clinical trials: A significant part of cancer care appeared first on Mayo Clinic News Network.

Regenerative Medicine Minnesota has awarded funding to three projects aimed at strengthening Minnesota's capabilities for developing and delivering therapies that replace, restore, rejuvenate or regenerate damaged cells, tissues or organs.

Co-led by the University of Minnesota and the Mayo Clinic, Regenerative Medicine Minnesota brings together the state's leading research institutions to accelerate breakthroughs and bring new therapies to patients across the state.

The funded projects were selected for their potential to overcome challenges that slow the development and delivery of new therapies. Each project aims to build sustainable, widely accessible resources to help move regenerative treatments from the lab to patients more quickly.

The projects are:

Derivation of Induced Pluripotent (Adult) Stem Cell Lines in Minnesota with Superior HLA Compatibility for Manufacturing Clinical Cell Therapy Products

James Dutton, Ph.D., University of Minnesota

This initiative tackles a key challenge in regenerative medicine: access to clinical-grade starting materials. The project will generate high-quality, regulatory-compliant induced pluripotent (adult) stem cell (iPSC) lines with less risk of the immune system rejecting the cells. These lines will be made available to researchers across Minnesota, enabling the development of versatile, cost-effective cell therapies that can benefit a broad range of patients. By building a local supply of standardized starting materials, the project provides a long-term advantage to Minnesota's research community.

The Genome Engineering for Regenerative Medicine (GERM) Consortium

David Largaespada, Ph.D., University of Minnesota

Addressing the critical need for quality and safety standards in gene-edited therapies, this new consortium will bring together academic and industry experts to establish best practices for gene delivery, editing and evaluation. The GERM Consortium will provide essential guidance and resources to ensure that genetically engineered therapies are developed with precision and safety. Through this collaborative effort, Minnesota will become a hub for innovation and regulatory compliance in cell and gene therapy.

Minnesota BRIDGE — Boosting Regenerative Medicine Innovation through Development, Growth, and Engagement

Melanie Graham, Ph.D., University of Minnesota

This project focuses on a major translational bottleneck: the lack of robust preclinical models. Minnesota BRIDGE will create a state-of-the-art translational research infrastructure that enables more predictive preclinical testing of regenerative therapies. By establishing this capability, Minnesota will become one of the few places in the nation equipped to accelerate therapy development with cutting-edge preclinical models — streamlining the path to clinical trials and patient care.

Together, these projects advance Regenerative Medicine Minnesota's goal of bringing new therapies to patients in Minnesota and beyond while establishing the state as a leader in regenerative medicine.

###

About Regenerative Medicine Minnesota

Regenerative Medicine Minnesota was established in 2014 by the Minnesota State Legislature to improve the health of Minnesotans by advancing regenerative medicine. This state-wide initiative opens new economic opportunities through commercialization of technologies and leverages the strengths of Minnesota institutions to position the state at the forefront of regenerative medicine. The initiative distributes approximately $4 million in funding statewide every year for research, commercialization, and clinical translation initiatives that improve or increase access to scientifically proven regenerative medicine throughout the state. Learn more at www.regenmedmn.org.

###

The post New awards aim to make Minnesota a leader in regenerative medicine appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — Simultaneous bariatric surgery and liver transplant for patients who are severely obese is safe and improves long-term health outcomes, according to a recent Mayo Clinic study. This combined approach offers a needed solution for these patients who are often denied a lifesaving liver transplant due to their weight.

The 10-year study, published in the Journal of Hepatology, compared patients who received only a liver transplant with those who underwent both a liver transplant and bariatric surgery.

The combined approach resulted in sustained weight loss, reduced risk of type 2 diabetes and lower risk of fatty liver disease recurrence. Importantly, the combined procedure posed no additional risks compared to liver transplant alone.

"We've been amazed by the transformation our patients experience," says Julie Heimbach, M.D., director of Mayo Clinic Transplant Center in Minnesota and the study's senior author. "This dual approach prevents long-term obesity complications like diabetes, heart disease and cancer, while also preventing fatty liver disease recurrence."

How obesity and liver disease are connected

The percentage of liver transplant candidates in the U.S. with obesity continues to climb, with more than 41% of candidates having a body mass index above 30 in 2022. Obesity puts people at risk of developing metabolic dysfunction-associated steatotic liver disease, or MASLD, formerly known as nonalcoholic fatty liver disease. It's a condition where excess fat accumulates in the liver, which can lead to inflammation, scarring and advanced liver disease. Patients with a body mass index of 40 are more likely to be denied a transplant due to their weight.

"Since MASLD is a leading cause of liver failure, it only makes sense to protect the precious, lifegiving new liver from the same damage that led to the patient needing a transplant in the first place. Safely combining the two procedures protects the transplanted liver and can provide profound health benefits to these patients," says Todd Kellogg, M.D., Mayo Clinic bariatric surgeon and the study's co-author.

What about using new prescription medications for weight loss?

New weight loss medications, such as GLP-1s, are being used to help some pre-transplant and post-transplant patients manage their weight. Still, Mayo Clinic experts say bariatric surgery remains an important option for patients with severe obesity due to its safety, proven effectiveness and lasting results. Another recent Mayo study related to kidney transplant patients supports this.

"The patients that we're talking about really have a significant amount of extra weight. The issue with the GLP-1 medications is they are effective in terms of weight loss as well as other benefits which are being identified, but they may not get these patients with severe obesity to their lasting goal of a healthier weight," Dr. Heimbach says.

Bringing together experts from different medical specialties is essential when treating these patients, says Ty Diwan, M.D., Mayo Clinic transplant surgeon and the study's co-author.

"This study shows that caring for these complex patients extends beyond the transplant itself," Dr. Diwan says. "Multidisciplinary care is required to maximize patient outcomes, and that is what we see in this data. By bringing together experts in very different fields, we've improved patient care and overall health outcomes."

Additional resources:

• Mayo Clinic Minute: Dual procedure combines liver transplant, bariatric surgery

###

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:

• Heather Carlson Kehren, Mayo Clinic Communications, newsbureau@mayo.edu

The post Study finds long-term health benefits from bariatric surgery and liver transplant appeared first on Mayo Clinic News Network.

This dual procedure is especially helpful for patients with metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease. MASLD happens when fat builds up in the liver, often without symptoms. It's mostly caused by obesity — defined as a body mass index (BMI) of 30 or higher. In advanced stages, MASLD can lead to serious liver damage that requires a transplant.

Watch: The Mayo Clinic Minute

Journalists: Broadcast-quality video (01:09) is in the downloads at the end of this post. Please courtesy: "Mayo Clinic News Network." Read the script.

"Metabolic-associated steatotic liver disease is the most common liver disease, not only in the United States but worldwide," says Dr. Heimbach.

As obesity rates rise, so does the need to treat patients with MASLD.

"When we have excess fat that builds up in the liver, this can lead to inflammation and scarring and even advanced liver disease," she says.

It won't cause complications for everyone, but, for some, it can progress to cirrhosis.

"When a patient develops cirrhosis, they can then need a liver transplant," Dr. Heimbach says.

And having extra weight can be a reason patients might not be eligible for transplant. At Mayo Clinic, the approach is to help patients with obesity as well as transplant.

"We consider both liver transplant and what's called a sleeve gastrectomy, which is a type of weight-loss operation that can be used as a tool to help patients be successful in managing not only their liver disease with a liver transplant, but their obesity with the sleeve gastrectomy," Dr. Heimbach explains.

The procedures are done simultaneously with multiple teams working together. Dr. Heimbach says it's about providing patients the care they need.

"I'm excited about what transplant offers to all of our patients, which is to be able to return to the life that they had before they got sick. And for patients who were carrying extra weight, not only are they healthy again, but now they're able to really fully enjoy and be fully participating in their life," she says.

Additional Resources:

• Study finds long-term health benefits from bariatric surgery and liver transplant

The post Mayo Clinic Minute: Dual procedure combines liver transplant, bariatric surgery appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — Every year, some mothers die after giving birth due to heart problems, and many of these deaths could be prevented. The ability to screen for heart weakness before pregnancy could play a crucial role in identifying women who may need additional care to improve pregnancy outcomes. Mayo Clinic researchers, led by Anja Kinaszczuk, D.O., and Demilade Adedinsewo, M.D., tested artificial intelligence (AI) tools, using recordings from an electrocardiogram (ECG) and a digital stethoscope, to find unknown heart problems in women of childbearing age seen in primary care.   

Study findings published in the Annals of Family Medicine show high diagnostic performance of these technologies to detect left ventricular ejection fraction below 50%, indicating heart muscle weakness. These tools were tested on two groups of women aged 18 to 49.  

• Group 1: 100 women already scheduled for an echocardiogram (the best test to evaluate heart muscle function). They also had a standard clinical ECG and digital stethoscope recording of the heart’s electrical activity and heart sounds.  

• Group 2: 100 women seen for routine primary care visits to see how often the AI tools would find heart problems.   

The AI-ECG demonstrated an area under the curve (AUC) of .94 while the AI digital stethoscope, Eko DUO, achieved an even higher AUC of 0.98, indicating strong diagnostic accuracy. In the second cohort, the prevalence of positive AI screening results was 1% for the AI-ECG and 3.2% for the AI-stethoscope. 

"Statistically, nearly half of pregnancies in this country are unplanned, and approximately 1% to 2% of women may have heart problems they don't know about. Our research findings suggest that these AI tools could be used to screen women before pregnancy, allowing for improved pregnancy planning and risk stratification, early treatment, and better health outcomes which addresses a critical gap in current maternal care," says Dr. Adedinsewo, a cardiologist and senior author of the study.  

This research builds upon earlier published studies, including a pilot prospective study evaluating AI digital tools to detect pregnancy-related cardiomyopathy among obstetric patients in the U.S. and a pragmatic randomized clinical trial of women in Nigeria who were pregnant or had recently given birth. Collectively, this research highlights the potential of AI to modernize cardiovascular screening, enabling earlier identification and management of heart muscle weakness in women of reproductive age. Further research is underway to explore the potential of using these technologies to screen for heart weakness in broader populations.  

Mayo Clinic has licensed the underlying technology to EKO Health for its digital stethoscope with embedded ECG electrodes and to Anumana for the 12-lead ECG. Mayo Clinic and some study authors have a financial interest in this technology. Mayo Clinic will use any revenue it receives to support its not-for-profit mission in patient care, education and research. 

### 

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 

The post AI-ECG tools can help clinicians identify heart issues early in women planning to have children  appeared first on Mayo Clinic News Network.

Mayo Clinic researchers have identified a potential new way to monitor the progression of high-grade gliomas, one of the most aggressive types of brain cancer. Their feasibility study suggests that a personalized blood test tailored to each patient's tumor DNA could provide a faster and less invasive way to determine if the cancer is advancing. 

Currently, clinicians rely on scans and surgical biopsies to monitor gliomas, but both methods have limitations. For example, scans often cannot distinguish tumor growth from treatment effects such as inflammation. Biopsies require invasive procedures, making them impractical for routine monitoring. 

This new approach, published in Clinical Cancer Research, may provide clinicians with another tool to monitor tumor changes over time and adjust treatment as needed. 

"This research builds on years of studying genetic rearrangements and gives us a deeper understanding of the molecular mechanisms driving gliomas."

George Vasmatzis, Ph.D.

Tracking DNA fragments of gliomas

The findings focus on tumor DNA fragments circulating in the blood. As gliomas grow, some glioma cells die, shedding pieces of their DNA into the bloodstream and leaving behind genetic markers that are unique to the tumor. 

However, gliomas release fewer DNA fragments into the blood compared to many other cancers. This is because of the blood-brain barrier, a natural brain defense that prevents many substances from leaving the brain.  

To overcome this limitation, researchers focused on DNA junctions, a type of tumor-specific DNA fragment that is present in higher quantities. By targeting these markers, researchers achieved greater sensitivity, enabling them to detect even the smallest signs of tumor progression. 

Unlike normal DNA, which follows a structured sequence, these DNA junctions form when the tumor's genetic material breaks and rearranges. The study found that these amplified DNA junctions, due to their higher numbers, may provide a clearer picture of disease progression. 

"This research builds on years of studying genetic rearrangements and gives us a deeper understanding of the molecular mechanisms driving gliomas," says George Vasmatzis, Ph.D., a lead author of the study and co-director of the Biomarker Discovery Program at Mayo Clinic's Center for Individualized Medicine and Mayo Clinic Comprehensive Cancer Center. "It offers new possibilities for patient-specific monitoring and targeted interventions." 

Detecting tumor DNA

In the study, researchers analyzed samples from patients with high-grade gliomas. They used whole genome sequencing to map each tumor's unique genetic blueprint and pinpointed patient-specific DNA junctions. Researchers then developed personalized blood tests to search for these genetic markers in plasma. 

"By tracking each tumor's distinct molecular signature, we're aiming to shift from a reactive approach to one that's far more proactive,"

Terry Burns, M.D., Ph.D.

The test detected tumor DNA in approximately 93% of the cases where these DNA junctions were present. In some patients, tumor DNA levels in the blood rose before MRI scans showed any changes — offering a potential early signal for disease progression.

Dr. Vasmatzis collaborated with Mayo Clinic neurosurgeon Terry Burns, M.D., Ph.D., bridging the gap between cutting-edge research and clinical practice. 

"By tracking each tumor's distinct molecular signature, we're aiming to shift from a reactive approach to one that's far more proactive," says Dr. Burns, a co-author of the study. "This research could lay the groundwork for tools that help clinicians make the most informed treatment decisions as early as possible." 

Future studies will evaluate how well blood-based tumor tracking correlates with glioma progression across a larger group of patients. 

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

The post Mayo Clinic researchers reveal personalized approach to brain cancer monitoring  appeared first on Mayo Clinic News Network.

Video: A healthy liver transitions to cirrhosis, illustrating a potential outcome of metabolic dysfunction-associated steatotic liver disease — formerly known as nonalcoholic fatty liver disease — which affects nearly one-third of the global population. Getty Images.

Researchers at Mayo Clinic's Center for Individualized Medicine have made a groundbreaking discovery: a rare genetic variant that can directly cause metabolic dysfunction-associated steatotic liver disease, formerly known as nonalcoholic fatty liver disease. It is one of the most common diseases in the world. 

Until now, scientists believed the disease resulted from a combination of genetic and environmental factors. This study, published in Hepatology, reveals that in some cases, a single inherited variant can be the primary driver.  

The researchers identified this variant in the MET gene, which regulates liver repair and fat metabolism. When the gene malfunctions, fat accumulates in liver cells and triggers inflammation. Over time, this leads to fibrosis and scarring, which stiffens the liver. In severe cases, the disease progresses to cirrhosis, resulting in irreversible liver damage or liver cancer. 

Metabolic dysfunction-associated steatotic liver disease affects about one-third of adults worldwide. Its advanced form, metabolic dysfunction-associated steatohepatitis, is expected to become the leading cause of cirrhosis and the reason for liver transplants in the coming years. 

"This discovery opens a window into how rare inherited genetic variants can drive common diseases," says Filippo Pinto e Vairo, M.D, Ph.D., a lead author and medical director of the Program for Rare and Undiagnosed Diseases at Mayo Clinic's Center for Individualized Medicine. "It provides new insights into this disease pathogenesis and potential therapeutic targets for future research."  

A hidden error in the genetic code 

The discovery emerged from the genomic data of a woman and her father with metabolic dysfunction-associated steatohepatitis. They had no history of diabetes or high cholesterol, two common risk factors for fat buildup in the liver.  

With no clear explanation, researchers examined the DNA from more than 20,000 genes to find answers. They found a small but potentially significant error in the MET gene. 

In collaboration with the Medical College of Wisconsin's John & Linda Mellowes Center for Genomic Sciences and Precision Medicine, led by Raul Urrutia, M.D., the scientists determined that the mutation disrupted a critical biological process. 

Genes are made up of chemical letters that provide instructions for the body's functions. In this case, a single swapped letter — among thousands — scrambled the message, preventing the liver from properly processing fat. This rare variant, found in the family, has not been reported in existing literature or public databases. 

"This study demonstrates that rare diseases are not rare but often hidden in the large pool of complex disorders, underscoring the immense power of individualized medicine in identifying them, and enabling the design of advanced diagnostics and targeted therapies," Dr. Urrutia says.  

Tracing the genetic variant impact

To explore the variant's broader impact, researchers turned to Mayo Clinic's Tapestry study, a large-scale exome sequencing effort aimed at uncovering genomic drivers of disease. The Tapestry study analyzed germline DNA from over 100,000 participants across the U.S., creating a comprehensive genomic data repository that supports research into both well-known and emerging health conditions.  

Among nearly 4,000 adult Tapestry participants with metabolic dysfunction-associated steatotic liver disease, about 1% carried rare, potentially causative variants in the same MET gene. Of these, nearly 18% had variants in the same critical region as the initial woman and her father, further supporting its role in liver disease.  

"This finding could potentially affect hundreds of thousands, if not millions, of people worldwide with or at risk for metabolic dysfunction-associated steatotic liver disease," says Konstantinos Lazaridis, M.D., a lead author and the Carlson and Nelson Endowed Executive Director for the Center for Individualized Medicine. 

Dr. Lazaridis emphasized the significance of this discovery as it relates to the Tapestry study's impactful contributions.  

"Once a pathogenic variant is discovered, interrogating our Tapestry data repository is giving us a clearer lens into the hidden layers of disease, and this discovery is one of the first to demonstrate its scientific significance," Dr. Lazaridis says. "This finding highlights the profound value of studying familial diseases and the merit of large-scale genomic datasets, which can reveal rare genetic variations with broader implications for population health." 

Advancing genomics to transform care

This discovery also reflects the importance of integrating genomics into clinical care at Mayo Clinic, where teams use advanced technologies to help solve complex medical mysteries.  

Since its launch in 2019, the Program for Rare and Undiagnosed Diseases has helped more than 3,200 patients with complex and serious conditions gain access to comprehensive genomic testing. It collaborates with nearly 300 clinicians from 14 divisions across the enterprise to bring precision diagnostics to patients with rare conditions, including rare liver diseases. 

Future studies will explore how this genomic discovery in metabolic dysfunction-associated steatotic liver disease can inform targeted treatments and improve disease management. 

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

The post Groundbreaking discovery links inherited mutation to fatty liver disease appeared first on Mayo Clinic News Network.

A new Mayo Clinic study finds that people with Tourette syndrome have about half as many of a specific type of brain cell that helps calm overactive movement signals as people without the condition. This deficit may be a key reason why their motor signals go unchecked, leading to the involuntary tics that define the disorder. 

Published in Biological Psychiatry, the study is the first to analyze individual brain cells from people with Tourette disorder. The findings also shed light on how different types of brain cells may interact in ways that contribute to the syndrome's symptoms. 

"This research may help lay the foundation for a new generation of treatments," says Alexej Abyzov, Ph.D., a genomic scientist in Mayo Clinic's Center for Individualized Medicine and a co-author of the study. "If we can understand how these brain cells are altered and how they interact, we may be able to intervene earlier and more precisely." 

Tourette disorder is a neurodevelopmental condition that typically begins in childhood. It causes repeated, involuntary movements and vocalizations such as eye blinking, throat clearing or facial grimacing. Nearly 1 in 162 children in the U.S. have Tourette syndrome, according to the Centers for Disease Control. While genetic studies have identified some risk genes, the biological mechanisms behind the condition have remained unclear. 

A close look at key brain cells

To better understand what's happening in the brain with Tourette syndrome, Dr. Abyzov and his team analyzed more than 43,000 individual cells from postmortem brain tissue of people with and without the condition.

They focused on the basal ganglia, a region of the brain that helps control movement and behavior. In each cell, they looked at how genes were working. They also analyzed how changes in the brain's gene-control systems might trigger stress and inflammation.

First, they found in people with Tourette syndrome a 50% reduction in interneurons. These brain cells help calm excess signals in the brain's movement circuits.

They also observed stress responses in two other brain cell types. Medium spiny neurons make up most of the cells in basal ganglia. They help send movement signals and showed reduced energy production. Microglia, the brain's immune cells, showed inflammation. The researchers found a close link between the two responses, suggesting the cells may interact in Tourette disorder.

"We're seeing different types of brain cells reacting to stress and possibly communicating with each other in ways that could be driving symptoms," says Yifan Wang, Ph.D., co-author of the study.  

The study points to changes in DNA regions that control when genes turn on and off as a possible cause of brain cell changes in Tourette disorder. 

"Tourette patients seem to have the same functional genes as everyone else but the coordination between them is broken," says Dr. Abyzov. 

Next, the researchers plan to study how these brain changes develop over time and look for genetic factors that may help explain the disorder. 

The researchers conducted the study in collaboration with the lab of Flora M. Vaccarino, M.D., at Yale University. For a complete list of authors, disclosures and funding, review the study. 

The post Mayo Clinic uncovers brain cell changes that could explain Tourette syndrome  appeared first on Mayo Clinic News Network.