ROCHESTER, Minn. — Mayo Clinic researchers have developed a new artificial intelligence (AI) tool that helps clinicians identify brain activity patterns linked to nine types of dementia, including Alzheimer's disease, using a single, widely available scan — a transformative advance in early, accurate diagnosis. 

The tool, StateViewer, helped researchers identify the dementia type in 88% of cases, according to research published online on June 27, 2025, in Neurology, the medical journal of the American Academy of Neurology. It also enabled clinicians to interpret brain scans nearly twice as fast and with up to three times greater accuracy than standard workflows. Researchers trained and tested the AI on more than 3,600 scans, including images from patients with dementia and people without cognitive impairment. 

This innovation addresses a core challenge in dementia care: identifying the disease early and precisely, even when multiple conditions are present. As new treatments emerge, timely diagnosis helps match patients with the most appropriate care when it can have the greatest impact. The tool could bring advanced diagnostic support to clinics that lack neurology expertise. 

The rising toll of dementia 

Dementia affects more than 55 million people worldwide, with nearly 10 million new cases each year. Alzheimer's disease, the most common form, is now the fifth-leading cause of death globally. Diagnosing dementia typically requires cognitive tests, blood draws, imaging, clinical interviews and specialist referrals. Even with extensive testing, distinguishing conditions such as Alzheimer's, Lewy body dementia and frontotemporal dementia remains challenging, including for highly experienced specialists. 

StateViewer was developed under the direction of David Jones, M.D., a Mayo Clinic neurologist and director of the Mayo Clinic Neurology Artificial Intelligence Program.  

"Every patient who walks into my clinic carries a unique story shaped by the brain's complexity," Dr. Jones says. "That complexity drew me to neurology and continues to drive my commitment to clearer answers. StateViewer reflects that commitment — a step toward earlier understanding, more precise treatment and, one day, changing the course of these diseases." 

To bring that vision to life, Dr. Jones worked alongside Leland Barnard, Ph.D., a data scientist who leads the AI engineering behind StateViewer. 

"As we were designing StateViewer, we never lost sight of the fact that behind every data point and brain scan was a person facing a difficult diagnosis and urgent questions," Dr. Barnard says. "Seeing how this tool could assist physicians with real-time, precise insights and guidance highlights the potential of machine learning for clinical medicine." 

Turning brain patterns into clinical insight 

The tool analyzes a fluorodeoxyglucose positron emission tomography (FDG-PET) scan, which shows how the brain uses glucose for energy. It then compares the scan to a large database of scans from people with confirmed dementia diagnoses and identifies patterns that match specific types, or combinations, of dementia. 

Alzheimer's typically affects memory and processing regions, Lewy body dementia involves areas tied to attention and movement, and frontotemporal dementia alters regions responsible for language and behavior. StateViewer displays these patterns through color-coded brain maps that highlight key areas of brain activity, giving all clinicians, even those without neurology training, a visual explanation of what the AI sees and how it supports the diagnosis. 

Mayo Clinic researchers plan to expand the tool's use and will continue evaluating its performance in a variety of clinical settings. 

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:  

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

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ROCHESTER, Minn. — Little is known about what causes ovarian cancer, and there is no way to detect it early yet. About 75% of the time when someone is diagnosed with ovarian cancer, it has already progressed to stage 3 or stage 4, which means it has spread to other parts of the body. Mayo Clinic physicians, researchers and patients had been working together to learn more about this devastating disease when a 22-year-old patient, who has two rare genetic conditions that dramatically elevate lifetime cancer risk, came to Mayo Clinic.

The patient carries a hereditary BRCA2 mutation, which is one of the genes that causes hereditary breast and ovarian cancer (HBOC) syndrome, and a hereditary TP53 mutation, which causes Li-Fraumeni syndrome.

At Mayo Clinic, she was diagnosed with breast cancer. Imaging also revealed she had an ovarian cyst. Although the cyst was benign, she chose to have a mastectomy and hysterectomy with removal of her ovaries and fallopian tubes, a procedure called a bilateral salpingo-oophorectomy, because of her elevated cancer risk. Upon further examination, her Mayo Clinic physician and research team detected early, hidden changes in the cells lining her fallopian tubes, revealing signals that may point to the first signs of ovarian cancer before symptoms or visible lesions appear.

"Our team glimpsed a rare and revealing phenomenon in epithelial biology, uncovered through the cells of a young patient living with profoundly high-risk genetic conditions. Using cutting-edge, single-cell technologies, we traced how her epithelial cells were developmentally altered in ways that signaled a high risk for lethal ovarian cancer. These insights could pave the way for future strategies to detect the disease in its earliest, precancerous stages when prevention is still possible," says Nagarajan Kannan, Ph.D., director of the Stem Cell and Cancer Biology Laboratory at Mayo Clinic and co-lead author of this study published in JCO Precision Oncology.

Jamie Bakkum-Gamez, M.D., the patient's gynecologic oncology surgeon at Mayo Clinic, says she is determined to find a way to detect ovarian cancer earlier to help save more patients' lives.

"We know that the most aggressive and common form of ovarian cancer often actually starts in the fallopian tube. However, why the fallopian tube and how it starts are not yet known. Knowing how ovarian cancer begins and forms could not only lead to the development of earlier screening tools, but also more personalized risk-reduction strategies and improved guidance around the timing of preventive surgeries and fertility planning," says Dr. Bakkum-Gamez, who is a co-lead author of this study.

Watch: Dr. Jamie Bakkum-Gamez on revealing hidden signs of ovarian cancer risk

Journalists: Broadcast-quality sound bites are available in the downloads. Please courtesy: "Mayo Clinic News Network." Name super/CG: Jamie Bakkum-Gamez, M.D./ Gynecologic Oncology/Mayo Clinic

Together, Dr. Kannan and Dr. Bakkum-Gamez have established a living fallopian tube biobank at Mayo Clinic. The cells and tissues donated by patients help scientists study how ovarian cancer begins — cell by cell — directly in human tissue. From the patient specimens, organoids, or small versions of the fallopian tubes, can be grown. The biobank includes organoids from patients with average-to-high ovarian cancer risk and specializes in inherited cancer mutations like the ones associated with HBOC syndrome and Li-Fraumeni syndrome.

"The precise cellular origin of ovarian cancer remains one of the greatest unanswered questions in cancer prevention — limiting our ability to intervene early and save lives. This work lays the foundation for a new era of early detection and precision prevention for ovarian cancer, especially for patients with inherited risk such as BRCA mutations."

Nagarajan Kannan, Ph.D.

Ovarian cancer precursor

A healthy fallopian tube consists of two main types of epithelial cells: multiciliated cells that have hundreds of cilia, or hairlike appendages, that help move the fertilized egg through the fallopian tube and secretory cells that secrete fluids to nourish and protect the developing embryo. But in the fallopian tube cells collected from the patient with HBOC syndrome and Li-Fraumeni syndrome, the scientists saw something they had never seen before. Instead of the two types of epithelial cells, the secretory cells vastly outnumbered the multiciliated cells across the fallopian tube. They also found that secretory cells were driving chronic inflammation — an established contributor to cancer development.

"Through single-cell RNA sequencing, we could see the disruptions in the development of cells lining the fallopian tube lumen — findings that could help reshape how we understand and ultimately prevent ovarian cancer," says Megan Ritting, co-lead author and Mayo Clinic Graduate School of Biomedical Sciences doctoral candidate. Ritting spearheaded the use of cutting-edge genomic technology in this study.

Furthermore, oral contraceptives containing progestins, or synthetic analogs of the hormone progesterone that is produced by the ovaries, can be used to reduce ovarian cancer risk by up to 50%. However, Ritting and the research team were surprised to see that this patient's fallopian tube cells did not have any progesterone receptor proteins, which suggests oral contraceptives may not have been effective in reducing the patient's risk for ovarian cancer.

"With the generous partnership of patients who allow their cells to be studied using advanced technologies, including organoid models, we are making critical progress in understanding how these cancers develop. This work represents an important step toward identifying opportunities to develop preventive strategies, treatments and approaches that could reduce the risk of fallopian tube and ovarian cancers," says Dr. Bakkum-Gamez.

In the next steps of this research, using the living fallopian tube biobank, the scientists are investigating how and where earliest origins of ovarian cancer take root.

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

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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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ROCHESTER, Minn. — Millions of people are affected by chronic dry mouth, or xerostomia, an agonizing side effect of damaged salivary glands. While chemotherapy and radiation treatment for head and neck cancer are the most common causes of this, aging, certain medications and other factors, including diabetes, stroke, Alzheimer's disease and HIV/AIDS, can also cause chronic dry mouth. Currently, there is no cure for it.

Mayo Clinic researchers have established the world's first biobank of human salivary gland tissue-organoids that opens the door to research to find a cure.

"This unique biobank resource overcomes a major barrier we've faced in the field, namely: limited access to standardized salivary specimens suited for salivary gland regeneration research. This collection provides a foundation for regenerative therapy development, especially for radiation-induced chronic dry mouth," says Nagarajan Kannan, Ph.D., lead author of the study published in NPJ Regenerative Medicine. Dr. Kannan is also the director of the Mayo Clinic Stem Cell and Cancer Biology Laboratory.

Nearly 70% of patients with head and neck cancer who are undergoing radiation therapy experience permanent damage to their salivary glands. People with this condition experience diminished quality of life from a constant feeling like cotton is lining their mouths. Besides being uncomfortable, chronic dry mouth can lead to difficulties with chewing, tasting, speaking and swallowing. It also can cause tooth decay.

"Chronic dry mouth can extend long after radiation treatments are complete. It's among the top concerns I hear from patients with head and neck cancer. Unfortunately, there aren't many therapeutics available commercially for these patients," says co-author Jeffrey Janus, M.D., an ear, nose and throat specialist at Mayo Clinic in Florida.

One promising avenue of research is the cultivation of rare regenerative cells to greater numbers that can help people someday heal and grow new, healthy salivary gland cells. The biobank consists of specimens collected from 208 donors. From this repository, researchers have already found biomarkers for mature, saliva-producing cells, and with the help of a high-resolution protein map, they have identified the potential tissue origin of rare, self-renewing salivary cells.

The research team also developed a radiation injury model, which paired with the biobank, provides an integrated platform to discover new, personalized regenerative biotherapeutics.

This is a collaboration between Mayo Clinic Center for Regenerative Biotherapeutics, Department of Laboratory Medicine and Pathology and Department of Otolaryngology.

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

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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 Mayo Clinic researchers develop first salivary gland regenerative biobank to combat chronic dry mouth 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.

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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: 

• 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.

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.

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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.

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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.   

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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.

For Anthony Maita, 'Buddy' is not just any other dog.

"He's the best thing that's ever happened to me," says Anthony.

It's no wonder, considering Buddy was right by Anthony's side during one of the most challenging times of his life — when Anthony began having epileptic seizures.

Watch: When seizures don't stop: Anthony's battle against drug-resistant epilepsy

Journalists: Broadcast-quality video (2:38) is in the downloads at the end of this post. Please courtesy: "Mayo Clinic News Network." Read the script.

"I started having the seizures, noticeable seizures, and from there, it just started getting worse and worse," recalls Anthony.

It began after Anthony graduated from high school. He was making plans for his future and looking forward to attending college. That's when the seizures began.

Initially, the seizures were mild but quickly became more severe. "The experience (seizure) is like a loss of time, like a blank spot in your memory — like you're waking up without any recollection of what happened," says Anthony.

"The seizures were several times a week. His lips would be blue. His mouth would be blue," says Patricia Maita, Anthony's mother. "It so hard to see your child go through that and feel so helpless."

Doctors tried to manage Anthony's seizures with medication, but nothing worked. Eventually Anthony was diagnosed with drug-resistant epilepsy, or DRE.

In search of hope, Anthony's family turned to Mayo Clinic in Arizona.

"Up to a third of patients who develop epilepsy during their life will become resistant to medication," explains Jonathon J. Parker, M.D., Ph.D., a neurosurgeon at Mayo Clinic who specializes in treating the most serious and complex cases of epilepsy, including DRE.

"These patients have tried at least two medications, and they're still having seizures. At that point, we know the chances of seizure freedom unfortunately become very low, and that's when we start looking at other options," says Dr. Parker.

A battle for millions worldwide

Anthony is one of approximately 50 million people worldwide diagnosed with epilepsy. It is one of the most common neurological disorders globally. It is characterized by recurrent unprovoked seizures caused by abnormal electrical activity in the brain.

Of those diagnosed with epilepsy, approximately 30%, or 15 million people, are considered medication-resistant. Uncontrolled seizures often rob many people of their ability to live and function independently.

While it is rare, seizures can lead to sudden unexplained death in epilepsy, or SUDEP. "We know that more frequent seizures mean the patient is at higher risk of SUDEP, so that's why we are very aggressive about treating epilepsy with all the tools we have available," says Dr. Parker.

Current treatment options for patients with DRE include surgical procedures such as brain resection to remove a portion of the brain tissue responsible for generating seizures. A less invasive procedure involves laser ablation therapy that pinpoints and destroys abnormal brain tissue. While often effective, these surgical approaches carry the risk of possible side effects, such as memory impairment, motor deficits and speech difficulties. 

Neuromodulation is another surgical approach that uses electrical or magnetic stimulation to interrupt abnormal neural activity without removing brain tissue.

Unlocking new hope for patients

Now, a growing number of scientists across the globe are part of an innovative trend in research, investigating novel ways to treat DRE. It involves the use of regenerative medicine as a "reparative" approach to help the brain heal. 

Dr. Parker is the lead investigator of the first-in-human clinical trial at Mayo Clinic which studies the use of implanted specialized inhibitory brain cells as a potential reparative treatment for DRE. Dr. Parker's clinical trial is underway in Arizona.

Mayo Clinic in Arizona is one of 29 sites nationwide participating in the inhibitory brain cell implant clinical trial for patients with focal epilepsy, where seizures originate in a specific region of the brain. 

Anthony became Mayo Clinic's first patient to undergo the investigational brain cell implant. 

"We use a very minimally invasive technique where we inject the inhibitory cells through a pencil eraser-sized incision in the back of the head. Our hope is that, over time, these cells become part of the brain and help repair the neural circuitry, and reduce or prevent seizures without the side effects," says Dr. Parker. The cells are implanted in a one-time, single-dose procedure.

"Honestly, it was pretty easy," says Anthony. "I had no trouble with it." Anthony was discharged from the hospital the next day.

Doctors say it is still too early to determine whether the brain cell implant was effective, but they are hopeful.

"Anthony has been doing great since the procedure," says Dr. Amy Z. Crepeau, a neurologist at Mayo Clinic. "We have a great deal of optimism in regard to the potential of this brain cell therapy. Developing a safe and effective, minimally invasive treatment that does not carry the possible negative side effects could be a game changer in treating patients with DRE and improving their quality of life."

Tabitha's life-long struggle to control seizures

Tabitha Wilson lives in fear, never knowing when or where the next seizure will strike.

The Florida resident was diagnosed with epilepsy at the age of 2. She was placed on medication that adequately managed her seizures — until the week before her high school graduation. 

"I was 17 years old sitting in history class when the seizure happened," recalls Tabitha. "They had to load me up in an ambulance in front of the whole school."

Tabitha tried new types of medications, but the seizures only got worse.

"I fell down a flight of stairs, burned myself while cooking. I've completely blacked out and don't know where I am or who you are," says Tabitha. She was eventually diagnosed with drug-resistant epilepsy.

Tabitha underwent three brain surgeries to treat her DRE. Still, the seizures continued.

"I'll have good days and bad days. Some days, I'll have two, three, four seizures, back-to-back," says Tabitha.

Her uncontrolled seizures have robbed Tabitha of the ability to live independently. "I can't drive. I can't cook. I can't go swimming alone. I can't take a bath, only a shower and if someone is home with me," says Tabitha.

Watch: Tabitha Wilson shares what it's like to live with drug-resistant epilepsy.

Tabitha turned to Mayo Clinic in Florida where she learned about a clinical trial also investigating the potential of regenerative medicine as a possible treatment for DRE.

Dr. Sanjeet S. Grewal, director of stereotactic and functional neurosurgery at Mayo Clinic, is leading a team of researchers studying the use of implanted stem cells in conjunction with deep brain stimulation for patients like Tabitha.

Deep brain stimulation is one of the most recent FDA-approved methods of neuromodulation therapy for epilepsy. Studies show that patients who undergo deep brain stimulation experience median seizure reduction up to 70% after five years. However, Dr. Grewal says it is uncommon for patients to become seizure-free. 

"Unfortunately, neuromodulation doesn't give us the seizure freedom we want, and that's why we are trying to combine deep brain stimulation with stem cell therapy to see if we can increase the efficacy of neuromodulation," he says. 

Tabitha became the first patient to undergo the investigational treatment. Dr. Grewal says she is also the first person in the world to undergo surgery for deep brain stimulation and receive stem cell therapy in the thalamus in her brain as a potential treatment for DRE. 

Watch: Dr. Sanjeet Grewal, neurosurgeon, explains how Mayo researchers are leading a new trend in research for treating patients with drug-resistant epilepsy.

The clinical trial involves the use of mesenchymal stem cells, a type of adult stem cell that has anti-inflammatory properties. MSCs may also support tissue repair and healing. Further scientific research is needed to confirm their therapeutic potential in the field of regenerative medicine.

The MSCs used in the clinical trial are derived from fat tissue and created at the Human Cell Therapy Laboratory at Mayo Clinic in Jacksonville, Florida under the leadership of Abba Zubair, M.D., Ph.D., a pioneer in cell therapy.

Dr. Zubair's research teams have developed a cost-effective method of producing MSCs for use in potential treatments for conditions such as stroke.

Dr. Zubair has also led innovative research, including sending stem cells to the International Space Station to investigate how microgravity impacts their growth.

"My mission is to discover ways to address problems that patients have been struggling with and find a solution for them.
I believe the future is bright. "

Dr. Abba Zubair, Pioneer in Cell therapy, Mayo Clinic in Florida

Dr. Zubair has several research projects scheduled to launch into space in 2025.

"MSCs are what we call multipotent, meaning they can differentiate into different cell types based on where they're placed. If they are placed near blood vessels, they can become blood vessel types. If they're placed by heart cells, they can become heart cell types," explains Dr. Grewal.

The hope is the MSCs eventually become neural or brain cell types and interact in the part of the brain where the seizures occur. "It's called paracrine signaling, where they're releasing signals to the brain tissue around them and interacting in a way to try to repair that tissue."

Since undergoing the procedure, there has been an improvement in Tabitha's seizure management. However, Dr. Grewal says it is too early to know whether this is due to the deep brain stimulation, stem cells or both. 

Drs. Grewal and Parker say there is still a long road ahead to determine whether these cell therapies are proven safe and effective for patients with DRE. But they agree each day brings them one step closer to a potential treatment or cure for patients like Tabitha and Anthony.

"We've thought about this for generations, we just didn't have these technologies to enable it. Now we do," says Dr. Grewal. "So, whether it's wound healing, neurodegeneration, epilepsy or stroke, there are so many different studies going on investigating the potential of regenerative or reparative therapies."

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The post (VIDEO) When seizures don’t stop: The battle against drug-resistant epilepsy appeared first on Mayo Clinic News Network.

Mayo Clinic operates one of the largest clinical laboratories in the world. More than 87,000 samples pass through the labs from Mayo Clinic patients and Mayo Clinic Laboratories' clients per day. At Mayo Clinic Laboratories and the Department of Laboratory Medicine and Pathology (DLMP), these thousands of samples are tested for a large swath of molecules that can signal disease. Additionally, Mayo Clinic physicians and researchers develop new diagnostic tests every year. The innovation and capability to improve medicine fuels the work of clinical pathologist Akhilesh Pandey, M.D., Ph.D. 

"The fact that we, as researchers, can find a new biomarker associated with a disease, develop a test to find it sooner and implement it into clinical practice, places Mayo Clinic at the forefront of the medicine of the future," he says.  

Dr. Pandey's multidisciplinary research team consists of chemists and biochemists, molecular and computational biologists and experts in advanced biomedical instrumentation who push the boundaries of technology to develop more powerful tests to help detect and diagnose diseases earlier.

"Our lab is focused on problems and technologies where there is a direct and tangible path to discovering new findings that can be put into medicine in many ways, especially in terms of diagnostics. For us, it's all about translating research into the practice," he says.

He collaborates with more than 100 different researchers at Mayo Clinic to achieve this.

"DLMP consultants and staff are continually searching for ways to translate clinically relevant research findings into novel diagnostics that will provide our clinicians and patients the answers they need. Many of these findings come from our own investigators in DLMP or Mayo Clinic, but we also will keep abreast of advances from researchers worldwide. Our track record is impressive due to the efforts and creativity of consultants like Dr. Pandey and so many others," says Eric Hsi, M.D., chair of the Department of Laboratory Medicine and Pathology at Mayo Clinic.

Research and Practice 

One group of genetic disorders that is particularly challenging to diagnose is called sphingolipidosis, which stems from the harmful accumulation of sphingolipids, a type of lipid molecule. Tay-Sachs disease is a form of sphingolipidosis where these lipids build up in the brain and spinal cord, causing nerve cell damage.

Most tests for sphingolipidosis can only screen for one specific form of the disorder at a time, targeting about 10 molecules, which makes the process laborious and time-consuming for both clinicians and patients. 

Dr. Pandey and researcher Seul Kee Byeon, Ph.D., heard about this challenge from colleagues in Mayo Clinic's Department of Laboratory Medicine and Pathology. So they went to work designing a more efficient test.

The result: a single assay that can test for 47 different molecules linked to many kinds of sphingolipidosis, offering more efficient diagnostic testing.  

"It's a huge gain, especially for clinicians who may suspect a patient has a rare and serious genetic condition but may not know where in the pathway the problem lies," says Dr. Byeon, who is the lead author on a study reporting the findings in the journal Clinical Chemistry.

This new test is still in development but will be rolled out for use in the near future at Mayo Clinic Laboratories. Dr. Byeon is also working on the next iteration of this assay, which would target hundreds of lipids. 

From just one cell

Dr. Pandey's research teams in the Systems Biology and Translational Medicine Laboratory and the Advanced Diagnostics Laboratory use a sensitive but versatile technique called mass spectrometry to detect, identify and quantify molecules in lab samples, which can come from blood, tissue or other specimens.

In addition, Dr. Pandey's team conducts research using single-cell proteomics and single-cell lipidomics, which can uncover what proteins and lipids, respectively, are present in individual cells. They also apply a rapidly evolving approach called spatial biology to map where various molecules are in a specific tissue. 

The information gleaned from these analytical techniques can lead to the discovery of biomarkers for a variety of conditions, from genetic disorders to cancer. 

"We want to find the next generation of biomarkers and we have the technology to do it," he says. 

Dr. Pandey's multidisciplinary research team has several other notable projects underway aimed at advancing diagnosis and treatment for a variety of diseases and disorders including: 

• Multiple myeloma: Working to identify which patients with this blood cancer will respond to a certain class of drugs that stimulates the immune system to attack abnormal cells.
• Cholangiocarcinoma: Helping gastroenterologists detect this form of bile duct cancer using single-cell proteomics, which illuminate protein behavior in individual cells, with the goal of detecting this difficult-to-treat cancer earlier.
• Inherited metabolic disorders: Adapting a blood-based test that detects genetic defects in a complex chemical process known as glycosylation so that it can be used to detect metabolic changes associated with cancer. 
  

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

The post Advancing medicine one lab test at a time appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — A discovery by Mayo Clinic researchers may help explain why immunotherapy hasn't been helpful for many patients with metastatic colorectal cancer. In findings published in Clinical Cancer Research, the team identified specific proteins — fibronectin and smooth muscle actin — within colorectal cancer tissues that are associated with resistance to immunotherapy treatment.

Immunotherapy is a major advance in treating cancer, but many patients, including those with metastatic colorectal cancer, do not respond to it. Until now, researchers have not known why.

"We need predictive biomarkers to guide the selection of immunotherapy for patients," says medical oncologist and gastroenterologist Frank Sinicrope, M.D., the senior author of the study. "Identifying those who may have resistance to treatment can be useful, because then we can spare them from receiving treatment that may not be beneficial and could produce significant toxicities."

The research team used digital spatial profiling, an advanced technology that simultaneously analyzes the expression of multiple proteins and where they are located within tissues. This approach allowed researchers to zoom in to get a bird's eye view of a tumor that includes proteins both within and surrounding the tumor cells and how they interact.

Dr. Sinicrope compares the spatial tools to an aerial view of a neighborhood where one can see relationships between driveways, houses, yards and neighboring structures. Similarly, this detailed view provides physicians and researchers with critical information about the proteins in and around a patient's cancer, potentially informing the best treatment for the patient. 

"We wanted to learn more about the patients who did not respond to immunotherapy. We investigated the leading edge of the tumor where cancer cells are invading and where the immune system is attempting to fight the cancer," says Dr. Sinicrope. "It's like a battle going on here and we're getting a snapshot into who is in attendance."

The researchers focused on 10 regions at the invasive margin of a tumor. They applied digital spatial profiling to investigate 71 distinct proteins in both the tumor's epithelial compartment and the surrounding stromal compartment. Fibronectin and smooth muscle actin are two extracellular matrix proteins that were found in the epithelial region of the tumor and were associated with resistance to immunotherapy and shorter time before disease progression.

Upon further analysis, the researchers observed that cancer-associated fibroblasts were producing these proteins. The evidence, they say, suggests that these proteins can contribute to suppression of the anti-tumor immune response.

The discovery offers a step toward more personalized and effective colorectal cancer treatments.  

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

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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:  

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

The post Mayo Clinic researchers identify proteins linked to immunotherapy resistance in metastatic colorectal cancer appeared first on Mayo Clinic News Network.