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. 

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ROCHESTER, Minn. — A study published in Brain Communications highlights a new approach to treating drug-resistant epilepsy. Researchers at Mayo Clinic have developed an innovative deep brain stimulation (DBS) platform that was used to not only reduce seizures, but also improve memory and sleep — two common challenges for patients with epilepsy.

Epilepsy, a seizure disorder that affects about 50 million people worldwide, often disrupts memory, emotions and sleep. Many cases are drug-resistant, leaving people with limited treatment options. Researchers at Mayo Clinic found that low-frequency DBS not only reduced seizures, but it also improved memory and sleep.

"Using an implanted investigational device, the team continuously monitored brain activity with AI-driven seizure and sleep tracking," says Gregory Worrell, M.D., Ph.D., Mayo Clinic neurologist and co-lead author of the study. "A cloud-based platform simultaneously assessed participants' behavior, memory and mood at home. This real-time data enables precise tuning of stimulation settings, maximizing benefits while minimizing side effects."

"By using an implanted device that continuously monitors brain activity, we can detect seizures more accurately than patient-reported diaries in order to optimize deep brain stimulation in real-time and improve treatment," says Vaclav Kremen, Ph.D., Mayo Clinic researcher and co-lead author of the study.

The researchers monitored five patients with temporal lobe epilepsy throughout their DBS treatment. The system allowed patients to track their brain activity and symptoms remotely, providing doctors with detailed, real-world data to fine-tune treatments. This technology could lead to more effective treatments for drug-resistant epilepsy and could be expanded to treat other neurological and psychiatric disorders.

"Our study demonstrates the potential of emerging neurotechnology to treat human disease," says Jamie Van Gompel, M.D., Mayo Clinic neurosurgeon and co-author of the study.

"Combining neuroscience, engineering and artificial intelligence, our work is paving the way for more personalized and effective treatments for epilepsy and other brain disorders," says Dr. Worrell.

The study was supported by the National Institutes of Health — National Institute of Neurological Disorders and Stroke, Defense Advanced Research Projects Agency, and the CLARA project, which has received funding from the European Union's Horizon Europe research and innovation program.  The implanted devices were donated by Medtronic as part of the National Institutes of Health Brain Initiative Public-Private Partnership.

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

###

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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When Vicki Tennant came to Mayo Clinic for answers about her heart condition, she never expected to be at the center of a medical breakthrough. But her case led Mayo Clinic researchers to identify a previously undetectable genetic phenomenon.

Most genetic diseases are linked to protein-coding regions, which is also where standard testing has been focused. The discovery based on Tennant's case, published in Circulation: Heart Failure, was that disease-causing variants can hide in areas of DNA that don't make proteins.

Specifically, a tiny glitch in one of these regions, combined with a known mutation, was enough to cause Tennant's disease. 

"The level of care and expertise at Mayo Clinic is something I've never experienced," Tennant says. "It’s amazing to think that what they found in me could change how doctors diagnose others."

A clue hidden in the heart

In her home state of Iowa, Tennant had been diagnosed with hypertrophic cardiomyopathy, a genetic condition that thickens the heart muscle and increases the risk of heart failure. But her case didn't follow the usual pattern.

She had an irregular heartbeat that required several procedures to restore a normal rhythm, and she had also had a stroke. Her cardiologist in Iowa referred her to Mayo Clinic for further evaluation.

At Mayo Clinic, what began as a closer look at Tennant’s heart tissue by cardiologist Jeffrey Geske, M.D., quickly gained momentum. Pathologist, Joseph Maleszewski, M.D., examined the biopsy and identified microscopic abnormalities that indicated the need for further investigation.

Around the same time, Tennant underwent a routine gallbladder surgery in Iowa. A liver biopsy performed during that procedure also revealed abnormalities, prompting Tennant to ask her Mayo team to review the findings. That request helped deepen the investigation into the underlying cause of her health issues.

When standard clinical genetic testing did not yield an answer, Dr. Geske asked Naveen Pereira, M.D., a cardiovascular genomicist, to take a closer look at Tennant's DNA. Dr. Pereira searched Tennant's genome for hidden patterns and anomalies.

He found that Tennant had one known disease-causing mutation in a gene responsible for producing an enzyme that prevents substances from accumulating in the cell. Normally, two mutations are needed to cause a genetic condition called mucopolysaccharidosis type IIIA. But something still didn't add up — besides having only one variant, Tennant lacked some of the typical symptoms of the disease.

Dr. Pereira conducted additional lab tests to check for signs of the condition in her cells, however, which led to confirming it as her diagnosis.

Mucopolysaccharidosis type IIIA usually appears in early childhood and causes progressive neurological decline. But Tennant, in her 40s, had no signs of neurological issues. In her, the condition showed up as heart disease — an unexpected and atypical presentation that added to the mystery.

A genetic mystery unfolds

With unanswered questions remaining, Dr. Pereira expanded the team, bringing in experts from Mayo Clinic's Center for Individualized Medicine: Filippo Pinto e Vairo, M.D., Ph.D., medical director of Mayo Clinic’s Program for Rare and Undiagnosed Diseases; Eric Klee, Ph.D., the Everett J. and Jane M. Hauck Midwest Associate Director of Research and Innovation; and Laura Lambert, Ph.D., director of the Functional Omics Resource Laboratory.

The team applied advanced sequencing and analysis methods to search beyond the usual areas of the genome. That's when they made another discovery.

"We found a variant in a stretch of DNA located between two genes — it's a region often missed by standard genetic testing because it doesn't code for proteins," says Dr. Pinto e Vairo. "Now we had to prove it was actually disrupting how the gene worked and contributing to the disease in our patient."

To validate the finding, Dr. Lambert and the Functional Omics Resource Laboratory team used innovative, light-based methods to test whether the DNA change was interfering with how the gene worked.

"This gave us the functional proof we needed to confirm that this variant was actually causing disease," Dr. Lambert says.

Combined with the known mutation previously identified by Dr. Pereira, this hidden change provided the missing explanation for Tennant's condition.

"This finding is a testament to the transformative potential of looking beyond the expected," Dr. Klee says. "It underscores how advancements in genomics and technology are enhancing our ability to understand the impact of an increasing number of genetic changes."

Together, these insights revealed an entirely new way genetic disease can emerge and take shape.

"This discovery highlights the strength of integrating advanced genomic science with clinical expertise to solve some of medicine's most complex mysteries," says Dr. Pereira. "This finding could help change our approach and diagnose other patients with unexplained conditions, and expand the scope of precision medicine."

A long-awaited answer

For Tennant, the discovery has provided long-sought clarity. She enjoys working on her farm, spending time outdoors and operating her tractor — all activities she now approaches with a deeper understanding of her health.

While there is no cure for Mucopolysaccharidosis type IIIA with cardiac involvement, her diagnosis allows for more precise monitoring and offers hope for potential future treatments, including gene therapy.

"I also hope this helps someone else," Tennant says. "If sharing my story means someone gets diagnosed sooner, then it's all worth it."

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

The post Hidden mutation leads to groundbreaking genetic discovery 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 is taking epilepsy research in a bold new direction, exploring treatment approaches to help patients living with the most severe and difficult-to-treat forms of epilepsy. About 50 million people worldwide are impacted by epilepsy. Approximately 30% of patients, or about 15 million people, suffer with drug-resistant epilepsy (DRE). While some patients experience only a few seizures per month, others may endure hundreds each day — ranging from episodes that are mild to life-threatening. 

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.

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

Neurosurgeon Jonathon J. Parker, M.D., Ph.D., is the lead investigator of the first-in-human clinical trial at Mayo Clinic studying the use of implanted specialized inhibitory brain cells as a potential reparative treatment for DRE. The clinical trial is underway at Mayo Clinic in Arizona.

"This is an exciting time for regenerative medicine and the potential it may have for millions of people who suffer from the debilitating side effects of DRE," says Dr. Parker. "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.

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. 

Arizona resident Anthony Maita was the first person at Mayo Clinic to participate in the clinical trial. He underwent the one-time, single-dose procedure and was discharged from the hospital the next day. "I had no trouble with it," says Anthony. "My biggest hope is that, one day, I don't have to deal with this. My other biggest hope is that other people won't have to either."

It is still too early to determine whether the brain cell implant was effective for Anthony. Doctors are monitoring his progress closely. "Anthony has been doing great since the procedure," says Amy Crepeau, M.D., 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."

Another clinical trial is underway at Mayo Clinic in Florida investigating the potential of regenerative medicine as a reparative treatment for DRE. Researchers are exploring the use of implanted stem cells in conjunction with neuromodulation.

One of the most recent FDA-approved methods of neuromodulation therapy for epilepsy is deep brain stimulation. While patients who undergo deep brain stimulation experience median seizure reduction up to 70% after five years, it is uncommon for patients to become seizure-free. Sanjeet Grewal, M.D., director of stereotactic and functional neurosurgery at Mayo Clinic, is hoping to change that. "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," says Dr. Grewal. 

Dr. Grewal is the lead investigator of the clinical trial which involves the use of implanted adipose-derived mesenchymal stem cells (MSCs) as an adjunct to deep brain stimulation for DRE patients. MSCs are a special type of adult stem cell with anti-inflammatory properties that may also have potential for healing.

Many, like Dr. Grewal, hope MSCs will serve a pivotal role in the future of regenerative medicine to treat conditions like epilepsy. "There are some patients whose seizures are just much harder to treat with the technology we have today. Our hope is that by adding stem cells and their regenerative potential, we can increase treatment success," says Dr. Grewal.

The clinical trial is using MSCs derived from fat tissue and produced at the Human Cell Therapy Laboratory at Mayo Clinic in Florida under the leadership of Abba Zubair, M.D., Ph.D. His research teams have developed a cost-effective method of producing MSCs for use in potential treatments for conditions such as stroke and osteoporosis. "My mission is to discover ways to address problems that patients have been struggling with and find a solution for them. I want to give them hope," says Dr. Zubair. "I truly believe the future is bright."

"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. It is hoped the MSCs in Dr. Grewal's clinical trial will become neural or brain cell types and interact in the part of the brain where 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."

Tabitha Wilson began having seizures at the age of 2. The Florida resident says her seizures were well controlled until her mid-20s when her medication stopped working. Tabitha tried numerous other medications and underwent three brain surgeries, none of which provided the relief she needed.

"There are days when I'll have two, three or four seizures, back-to-back," says Tabitha. "I fell down a flight of stairs. I've burned myself while cooking. I've completely blacked out and don’t know where I am." Like many people who have epilepsy, Tabitha says uncontrolled seizures have robbed her ability to live independently. "I can't drive, can't cook or swim alone. I can't take a bath, only a shower and someone has to be in the house," says Tabitha.

Tabitha became the first person to participate in the Florida clinical trial. 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. "I'm willing to try everything and anything to get some sort of control over these seizures because I've been living with this for so long," says Tabitha. "I hope to be a mother someday."

Since the surgery, Dr. Grewal says there has been an improvement in Tabitha's seizure management. However, he 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 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 even a 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."

Press kit, including b-roll, photos and interviews, available here.

###

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:

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

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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.

A comprehensive review published by Mayo Clinic researchers advances the understanding of Autosomal Dominant Polycystic Kidney Disease (ADPKD), the most common inherited form of kidney disease and the fourth leading cause of kidney failure worldwide.

Published in the Journal of the American Medical Association (JAMA), the review advances the understanding of ADPKD, which accounts for 5-10% of kidney failure in the U.S. and Europe. Its prevalence in the U.S. is 9.3 cases per 10,000 people.

"This is a vital resource for healthcare providers to stay informed about the latest diagnostic tools and treatment strategies to enhance patient care," says Fouad Chebib, M.D., a Mayo Clinic nephrologist and first author of the review. "It covers how the disease disrupts the normal functioning of the body, signs and symptoms of the disease, diagnosis, treatment and the likely outcome, equipping healthcare providers to manage this complex condition, improving the quality of life through timely, evidence-based care."

Physicians typically diagnose ADPKD in patients who are between the ages of 27 and 42. The disease causes fluid-filled cysts to grow on the kidneys, leading to kidney failure. Over 90% of people over age 35 diagnosed with ADPKD also present with multiple liver cysts, which can cause discomfort or pain.

ADPKD symptoms can vary from person to person. Some people may not have any symptoms, while others may experience high blood pressure, pain in the back or side, blood in the urine, frequent urinary tract infections and kidney stones. 

Hypertension affects 70-80% of people with ADPKD, and 9-14% of them develop brain aneurysms (a weakened and bulging area in the wall of a blood vessel), which have a low rupture rate.

A change in one of two genes, PKD1 (78%) or PKD2 (15%), causes most cases of ADPKD. If a person has one of these changes, they have a 50% chance of passing the condition on to their children. However, 10-25% of people have a genetic alteration not inherited from either parent.

The review provides practical guidance on managing blood pressure, sodium intake, hydration and lifestyle changes to delay complications such as kidney failure, liver cysts and hypertension to slow disease progression.

A key tool in managing the disease is the Mayo Imaging Classification (MIC), which predicts the severity of the disease based on a person's kidney size and growth rate. Higher MIC classifications indicate faster growth and an earlier need for kidney replacement (dialysis or kidney transplantation). Roughly half of ADPKD patients need kidney replacement therapy by age 62.

The review also explores the use of novel therapies, such as the drug tolvaptan, recently approved by the Food and Drug Administration to slow kidney function decline for high-risk adults at risk of rapidly progressing ADPKD.

"This drug improves care and paves the way for future therapies that enhance the quality of life and delay kidney failure," explains Neera Dahl, M.D., Ph.D., Mayo Clinic nephrologist and senior author of the review.

The review recommends that a kidney specialist who manages patients with ADPKD should share decision-making with the patient regarding genetic testing, treatments, monitoring and aneurysm screening. This collaborative approach recognizes the importance of the physician's medical expertise and the patient's values, preferences, and goals. It also says patients with ADPKD should be aware of the symptoms of ruptured aneurysms (sudden, severe headache) and the need for immediate medical attention should they experience those symptoms.

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

The post Autosomal Dominant Polycystic Kidney Disease: Early intervention and lifestyle crucial appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — A new study by Mayo Clinic Comprehensive Cancer Center researchers found that the presence of a specific genetic mutation — KRAS circulating tumor DNA (ctDNA) — strongly indicates a higher risk of cancer spread and worse survival rates for patients with pancreatic ductal adenocarcinoma (PDAC). The mutation was identified using a readily available and clinically approved blood and abdominal fluid test.

PDAC is an aggressive form of cancer that is often difficult to diagnose. Most patients already have cancer spread to other parts of their body when initially diagnosed, and current tests often miss this hidden spread. This makes it challenging to determine the best treatment strategy. The findings, published in the Annals of Surgical Oncology, may help identify patients who are more likely to have cancer spread to other parts of the body, therefore providing doctors and patients with the right information to make informed decisions about treatment.

"This is a major advancement for pancreatic ductal adenocarcinoma," says Mark Truty, M.D., hepatobiliary and pancreatic surgical oncologist within Mayo Clinic's Department of Surgery. Dr. Truty is senior author of the study. "We've had this genetic testing available for a number of years, however, we did not know the significance of the results or how to interpret them. Having the KRAS status will allow the patient and their provider to make better decisions about their individual cancer treatment."

The prospective cohort study, involving nearly 800 patients — the largest patient series to date in the literature using ctDNA — found that 20%-30% of patients with PDAC have detectable mutant KRAS ctDNA in the blood and/or peritoneum, and that those without any previous treatment, such as chemotherapy, had the highest incidence. Thus, the study suggests that ctDNA assays should be performed prior to treatment to have the highest yield.

The researchers examined data between 2018 and 2022. Blood sample tests revealed that 104 patients (14%) had KRAS ctDNA mutation. These patients were more likely to develop advanced, spreading cancer and had a lower survival rate. Further testing of fluid from around the abdominal cavity in 419 patients showed similar results: 123 (29%) had the marker, and these patients also experienced worse outcomes. The presence of this marker, whether in blood or abdominal fluid, indicated a poorer prognosis.

The study highlights that while surgery is the only known cure, most patients experience cancer spread after surgery. The test helps identify patients less likely to benefit from surgery alone, guiding treatment decisions towards chemotherapy and/or radiation before surgery. For patients without the KRAS mutation (approximately 10% of cases), the test is less conclusive and other tests are needed.

"Historically, we've known that KRAS mutations are associated with a more biologically aggressive pancreatic cancer," says Jennifer Leiting, M.D., hepatobiliary and pancreatic surgeon within Mayo Clinic's Department of Surgery. Dr. Leiting is first author of the study. "But this large study gives us a much clearer understanding of how to interpret the test results and use them to improve patient care. It allows for more accurate staging at diagnosis, leading to better treatment decisions."

The researchers suggest that this test should become a standard part of the initial diagnosis for PDAC, enabling more personalized risk stratification and effective treatment plans.

"This improved diagnostic capability offers hope for patients and their families facing this challenging disease," says Dr. Truty. "It's optimistic to see how advances in genetic testing are directly helping our patients."

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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, newbureau@mayo.edu

The post Mayo Clinic researchers identify a measurable genetic mutation as a significant predictor of metastasis and survival in pancreatic cancer appeared first on Mayo Clinic News Network.

Every rare disease tells a story. Understanding how one unfolds — how it develops and evolves — is often the first step toward treating it. A small genetic error, a malfunctioning cell or a breakdown in a biological process can set disease in motion. But for many rare conditions, the course of progression remains unwritten. 

A groundbreaking natural history study led by researchers at Mayo Clinic's Center for Individualized Medicine and Department of Clinical Genomics aims to change that, advancing research for one rare disease with the potential to benefit many others. 

At the center of this effort is autosomal dominant leukodystrophy, a rare, hereditary neurodegenerative disorder. It is driven by a single genetic variant that causes an abnormal buildup of a protein. This disrupts nerve cell function and the brain's signaling network. Over time, this damage leads to a slow decline in movement, balance and essential body functions. 

A road map for research and treatment

This extensive study will track the disease from its earliest stages to advanced progression in patients from around the world. By analyzing patient medical records, brain imaging scans, genetic data, neurological assessments and more, researchers will develop a comprehensive dataset to identify key biological markers in people with the disease.  

These insights will serve as a foundation for future clinical trials. 

"Genetic therapies are increasingly becoming a reality for rare diseases, providing hope of a treatment that can address the root cause of the disease," says Margot Cousin, Ph.D., the study's lead investigator and director of the Center for Individualized Medicine's N-of-1 Therapeutics program. "We need to have systems in place to study these disorders so we can bring these therapies into clinical practice efficiently." 

"Genetic therapies are increasingly becoming a reality for rare diseases, providing hope of a treatment that can address the root cause of the disease."

mARGOT cOUSIN, pH.d.

What makes this disease so challenging?

Autosomal dominant leukodystrophy is classified as an ultra-rare disease, meaning it affects a small number of people worldwide. Fewer than 50 families have been identified, but researchers believe many cases go undiagnosed due to its similarities to other neurological conditions and limited access to genetic testing.  

Because it is so rare, most clinicians will never encounter a patient with autosomal dominant leukodystrophy (ADLD). When they do, the disease can be difficult to recognize, as its symptoms resemble other neurological disorders that affect the brain's protective nerve coating. This often leads to misdiagnosis and delays in care. 

Further, the type of genetic alteration that causes autosomal dominant leukodystrophy may not be detected using some common genetic testing methodologies, putting even more importance on the clinical recognition of the disease. Researchers emphasize the need to increase awareness of the disease among neurologists to help patients receive an accurate diagnosis sooner. 

How the study works

This natural history study is a collaboration with Children's Hospital of Philadelphia through the Global Leukodystrophy Initiative. This initiative has extensive expertise and infrastructure needed to capture and analyze data on autosomal dominant leukodystrophy at depth. 

Mayo Clinic researchers are working within this collaboration to improve how the disease is studied and to ensure data collection meets the highest clinical research standards.  

"We are creating a dedicated clinical and research infrastructure for identifying patients earlier so they can receive the highest level of multidisciplinary care."

Radhika Dhamija, M.B.B.S.

This study is also supported by the ADLD Center, a patient advocacy group, whose mission is to support research on the disease's pathology and therapy. The center provides patients, caregivers and families with essential resources and a strong support network.  

Improving diagnosis and clinical care

Alongside this natural history study, Mayo Clinic has established the Autosomal Dominant Leukodystrophy Clinical Care Center, dedicated to diagnosing and managing this disease. The center is led by Radhika Dhamija, M.B.B.S., a neurologist and medical geneticist in the Mayo Clinic Department of Clinical Genomics. This clinical care center coordinates care across neurology, urology, radiology, genomics and other specialties to provide the highest level of care for patients. 

"We are creating a dedicated clinical and research infrastructure for identifying patients earlier so they can receive the highest level of multidisciplinary care," says Dr. Dhamija. "This is about transforming the future of how we approach rare neurogenetic diseases." 

A model for future rare disease research

Mayo Clinic researchers see this natural history study on autosomal dominant leukodystrophy as a model for accelerating research in other ultra-rare conditions that remain understudied due to small patient populations. 

"We're building a framework that brings scientific clarity to diseases that have remained long overlooked," Dr. Cousin says.  

The post Mayo Clinic launches landmark study on rare neurological disease  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.

### 

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.