In a laboratory at Mayo Clinic, a machine that looks strikingly similar to a desktop printer is quietly reshaping the future of dermatology. Instead of ink, it dispenses living human cells. Instead of paper, it builds tissue — layer by layer — replicating one of the body's most complex organs: skin.

For Saranya Wyles, M.D., Ph.D., a dermatologist and researcher at Mayo Clinic, the journey into 3D bioprinting began not with an ambitious plan to reinvent tissue engineering, but with a practical problem. Her team needed a better way to test new therapies.

"We were trying to find a preclinical model to develop an FDA application," Dr. Wyles explains. Traditional approaches rely heavily on animal testing, but skin biology varies widely across species. Even commonly used preclinical models fall short when it comes to mimicking human skin conditions such as eczema.

At the same time, alternatives such as donated human skin samples — often surgical waste — can only survive for a few days in the lab. That limitation makes it difficult to study chronic diseases or long-term treatment effects.

Faced with these constraints, Dr. Wyles and her team asked a bold question: What if they could build human skin from scratch?

From printer to patient-specific model

The answer took shape through 3D bioprinting, an emerging technology that uses "bioinks" — mixtures of living cells and supportive materials — to construct tissues.

The concept sounds deceptively simple. Much like a standard printer uses different color cartridges, a bioprinter uses different cell types. In the case of skin, that includes fibroblasts, keratinocytes and melanocytes — the essential building blocks of the dermis and epidermis layers of the skin.

But translating that concept into living tissue proved anything but simple. Early attempts produced structures that looked nothing like real skin. "It was like a cartoon version," Dr. Wyles recalls. "Not even close."

What followed was nearly a year of intensive troubleshooting, bringing together clinicians, biomedical engineers and tissue engineers in a collaborative effort. The challenge wasn't just printing cells — it was keeping them alive, functional and organized.

Each cell type has its own needs, from nutrients to mechanical conditions. "It's like roommates," Dr. Wyles says. "They all want different things."

The team had to design new culture systems, optimize materials and even fine-tune the physical "stretch" of the printed tissue to mimic natural skin. These details matter. Skin's elasticity affects everything from wound healing to itch and aging. Gradually, iteration by iteration, the model improved.

Building skin, layer by layer

Today, the process resembles a carefully choreographed construction project. First, the printer lays down the dermis — the deeper layer of skin — using fibroblasts embedded in a collagen scaffold. After several days of maturation, the epidermis is printed on top, forming the outer protective layer.

The result is a structured tissue that mirrors key features of human skin, including stratified layers and pigment-producing cells. Crucially, the model uses entirely human-derived components, including a plant-based recombinant collagen that avoids the variability and immune risks associated with animal-derived materials.

The printed tissue can survive for weeks — far longer than traditional skin explants — allowing researchers to study disease progression and treatment responses over time. And because it's printed, it can be replicated with remarkable consistency.

"No two preclinical models are exactly the same," Dr. Wyles notes. "But we can print hundreds of nearly identical samples."

Improving how therapies are tested

The implications of this technology extend far beyond the lab bench. Preclinical testing has long been a cornerstone of drug development, yet it remains an imperfect predictor of how therapies will perform in humans — nearly 90% of drugs that succeed in preclinical testing ultimately fail in clinical trials.

Bioprinted human skin models offer a promising alternative — one that is not only more biologically relevant, but also faster, more scalable and more ethical.

"From both an ethical and a financial standpoint, the difference is enormous," Dr. Wyles says.

Regulators are beginning to take notice. The Food and Drug Administration has already engaged with the Mayo Clinic team on the technology, reviewing data demonstrating that the printed skin can replicate both the structure and function of human tissue.

That includes side-by-side comparisons of patient skin and lab-grown models, showing similar cellular architecture and biological responses. As a result, the model has been recognized as a promising alternative in certain preclinical contexts — potentially reducing the need for large animal studies.

Toward personalized and precision dermatology

Beyond its applications in preclinical research, the technology opens the door to a more personalized approach to medicine. Researchers are now developing ways to create patient-specific "maps" of skin by analyzing biopsies at a molecular level. These maps capture everything from cell distribution to markers of aging, such as cellular senescence.

Using this information, the team can program the bioprinter to recreate an individual's skin in the lab.

"We can essentially print your skin based on your own biological blueprint," Dr. Wyles says.

That capability could transform how treatments are developed and tested — allowing scientists to evaluate therapies on models that reflect specific patients, populations or conditions. It also has implications for studying aging, pigmentation and diseases such as atopic dermatitis, which can vary widely across individuals and skin types.

Expanding complexity

The current models represent a significant advance, but they are only the beginning. Human skin is a highly complex organ, responsible not just for protection, but also for sensation, temperature regulation and immune function. To more fully replicate that complexity, the Mayo team is working to add new features to their printed tissues.

Future versions may include blood vessels, immune cells and nerve structures — elements that would enable even more realistic modeling of disease and drug response. Researchers also are developing pigmented models to better represent diverse skin tones, addressing a long-standing gap in dermatologic research.

"Skin of color is an area where we need better models," Dr. Wyles says.

From innovation to impact

As interest in the technology grows, so does demand. Pharmaceutical and cosmetic companies are already exploring collaborations, drawn by the potential to accelerate product development while reducing reliance on animal testing.

To meet that demand, Mayo Clinic is working to scale the technology through collaborations and licensing, while continuing to refine the science.

At the same time, Dr. Wyles is mindful of the broader mission.

"We want to democratize this," she says. "The goal is to make it accessible so more people can use it, test more therapies and ultimately get treatments to patients faster."

A new frontier in regenerative medicine

The potential applications extend well beyond drug testing. Bioprinted skin could one day be used in regenerative medicine — for example, creating grafts for burn victims or patients with chronic wounds. It may also serve as a platform for studying aging and developing interventions to improve skin health over time.

For now, the focus remains on refining the models and expanding their capabilities.

"We're really just at the beginning of what this platform can do," Dr. Wyles says.

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ROCHESTER, Minn. — Mayo Clinic researchers have uncovered how aging "zombie cells" trigger harmful inflammation that accelerates a severe and increasingly common form of fatty liver disease called metabolic dysfunction-associated steatohepatitis (MASH). As obesity rates rise worldwide, MASH is projected to increase and is already one of the leading causes of liver transplantation. 

"Liver scarring and inflammation are hallmarks of MASH. If left untreated, it can progress to liver cancer. This is why it's so important to understand the mechanisms driving the disease so that we can prevent it or develop more effective treatments," says Stella Victorelli, Ph.D., who is the lead author of the study published in Nature Communications.  

Dr. Victorelli and colleagues, who study aged or senescent "zombie" cells, identified a mechanism by which these cells drive liver scarring and inflammation. They found that small molecules called mitochondrial RNA, typically found within the cell's energy-producing mitochondria, can leak into the main part of the cell, where they mistakenly activate antiviral sensors called RIG-I and MDA5 — normally triggered when a virus infects a cell. In this case, the danger signal comes from the cell's own mitochondria, prompting a wave of inflammation that can damage nearby healthy tissue. 

When the researchers blocked the sensors, inflammation dropped sharply. The study also found that proteins BAX and BAK, which help open pores in the mitochondrial membrane, enable mitochondrial RNA to escape. In a preclinical MASH model, inhibiting BAX and BAK prevented RNA from escaping and was associated with less inflammation and healthier liver tissue. 

What are 'zombie' cells?

As we age, some cells enter senescence — a state in which they stop dividing but continue releasing inflammatory and tissue‑damaging molecules. When people are young, the immune system typically eliminates these senescent, or "zombie," cells. With age, however, they can persist and contribute to a range of age‑related health problems and diseases. 

While some research focuses on removing these cells, this team investigated how to quiet their harmful signals.  

"With age, we accumulate 'zombie' cells, which can lead to more disease," says João Passos, Ph.D., senior author of the study. "Our idea is that if we can quiet these cells earlier, we can prevent runaway inflammation and the development of many age‑related conditions, including liver disease. Understanding the mechanisms that drive disease allows us to target and delay those processes — potentially benefiting more than one condition." 

Dr. Passos and colleagues also are developing new technology to spatially map senescent cells throughout the body during aging. 

This research was conducted in partnership between the Robert and Arlene Kogod Center on Aging and the Center for Cell Signaling in Gastroenterology (C-SiG) at Mayo Clinic. 

The research is part of a larger effort at Mayo Clinic called the Precure initiative, which is focused on developing tools that empower clinicians to predict and intercept biological processes before they evolve into disease or progress into complex, hard-to-treat conditions. 

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

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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. — Mayo Clinic researchers have developed a new tool that can estimate a person's risk of developing memory and thinking problems associated with Alzheimer's disease years before symptoms appear. The research, published in The Lancet Neurology, builds on decades of data from the Mayo Clinic Study of Aging — one of the world's most comprehensive population-based studies of brain health.

The study found that women have a higher lifetime risk than men of developing dementia and mild cognitive impairment (MCI), a transitional stage between healthy aging and dementia that often affects quality of life but still allows people to live independently. Men and women with the common genetic variant, APOE ε4, also have higher lifetime risk.

Predicting Alzheimer's disease

Alzheimer's disease is marked by two key proteins in the brain: amyloid, which forms plaques, and tau, which forms tangles. Drugs recently approved by the Food and Drug Administration remove amyloid from the brain and can slow the rate of disease progression for people with MCI or mild dementia.

"What's exciting now is that we're looking even earlier — before symptoms begin — to see if we can predict who might be at greatest risk of developing cognitive problems in the future," says Clifford Jack, Jr., M.D., radiologist and lead author of the study.

The new prediction model combined several factors, including age, sex, genetic risk as associated with APOE genotype and brain amyloid levels detected on PET scans. Using the data, researchers can calculate an individual's likelihood of developing MCI or dementia within 10 years or over the predicted lifetime. Of all the predictors evaluated, the brain amyloid levels detected on PET scans was the predictor with the largest effect for lifetime risk of both MCI and dementia.

"This kind of risk estimate could eventually help people and their doctors decide when to begin therapy or make lifestyle changes that may delay the onset of symptoms. It's similar to how cholesterol levels help predict heart attack risk," says Ronald Petersen, M.D., Ph.D., neurologist and director of the Mayo Clinic Study of Aging, who is a co-author of the study.

The research stands apart because it draws from the Mayo Clinic Study of Aging, a long-running effort in Olmsted County, Minnesota, that tracks thousands of residents over time. The analysis for this study included data from 5,858 participants. Unlike most studies, Mayo researchers are able to continue following participants even after they stop actively taking part, using medical record data — ensuring nearly complete information about who develops cognitive decline or dementia.

"This gives us a uniquely accurate picture of how Alzheimer's unfolds in the community," says Terry Therneau, Ph.D., who led the statistical analysis and is the senior author of the study. "We found that the incident rate of dementia was two times greater among the people who dropped out of the study than those who continued to participate."

The study elevates the significance of MCI, which is the stage targeted by current Alzheimer's drugs that slow but do not stop progression.

While the new tool is currently a research instrument, it represents a major step toward more personalized care. Future versions may incorporate blood-based biomarkers, which could make testing more accessible.

The work was supported by the National Institute on Aging, the GHR Foundation, Gates Ventures and the Alexander Family Foundation.

The research is part of a larger effort at Mayo Clinic called the Precure initiative focused on developing tools that empower clinicians to predict and intercept biological processes before they evolve into disease or progress into complex, hard-to-treat conditions.

"Ultimately, our goal is to give people more time — time to plan, to act and to live well before memory problems take hold," says Dr. Petersen.

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:

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

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ROCHESTER, Minn. — When it comes to treating disease, one promising avenue is addressing the presence of senescent cells. These cells — also known as "zombie cells" — stop dividing but don't die off as cells typically do. They turn up in numerous diseases, including cancer and Alzheimer's disease, and in the process of aging. While potential treatments aim to remove or repair the cells, one hurdle has been finding a way to identify them among healthy cells in living tissue. 

In the journal Aging Cell, Mayo Clinic researchers report finding a new technique to tag senescent cells. The team used molecules known as "aptamers" — small segments of synthetic DNA that fold into three-dimensional shapes. Aptamers have the ability to attach themselves to proteins on the surfaces of cells. In mouse cells, the team found several rare aptamers, identified from among more than 100 trillion random DNA sequences, that can latch onto specific cell surface proteins and flag senescent cells.

"This approach established the principle that aptamers are a technology that can be used to distinguish senescent cells from healthy ones," says biochemist and molecular biologist Jim Maher, III, Ph.D., a principal investigator of the study. "Though this study is a first step, the results suggest the approach could eventually apply to human cells."

From a quirky idea to collaboration  

The project began with the quirky idea of a Mayo Clinic graduate student who had a chance conversation with a classmate.

Keenan Pearson, Ph.D. — who recently received his degree from Mayo Clinic Graduate School of Biomedical Sciences — was working under the mentorship of Dr. Maher, studying how aptamers might address neurodegenerative diseases or brain cancer.

A few floors away, Sarah Jachim, Ph.D., — who was also then conducting her graduate research — was working in the lab of researcher Nathan LeBrasseur, Ph.D., Director, Mayo Clinic Robert and Arlene Kogod Center on Aging, who studies senescent cells and aging.

At a scientific event, the two happened to chat about their graduate thesis projects. Dr. Pearson thought aptamer technology might be able to identify senescent cells. "I thought the idea was a good one, but I didn't know about the process of preparing senescent cells to test them, and that was Sarah's expertise," says Dr. Pearson, who became lead author of the publication.  

They pitched the idea to their mentors and to researcher Darren Baker, Ph.D., who investigates therapies to treat senescent cells. At first, Dr. Maher acknowledges, the students' idea seemed "crazy" but worth pursuing. The three mentors were excited about the plan. "We frankly loved that it was the students' idea and a real synergy of two research areas," says Dr. Maher.

The students obtained compelling results sooner than they expected and quickly recruited other student participants from the labs. Then-graduate students Brandon Wilbanks, Ph.D., Luis Prieto, Ph.D., and M.D.-Ph.D. student Caroline Doherty, each contributed additional approaches, including special microscopy techniques and more varied tissue samples. "It became encouraging to expend more effort," Dr. Jachim says, "because we could tell it was a project that was going to succeed."

Identifying attributes of senescent cells

 The study has provided new information about senescent cells beyond a way to tag them. "To date, there aren't universal markers that characterize senescent cells," says Dr. Maher. "Our study was set up to be open-ended about the target surface molecules on senescent cells. The beauty of this approach is that we let the aptamers choose the molecules to bind to."

The study found several aptamers latched onto a variant of a specific molecule on the surface of mouse cells, a protein called fibronectin. The role of this variant fibronectin in senescence is not yet understood. The finding means that aptamers may be a tool to further define unique characteristics of senescent cells.

Additional studies will be necessary to find aptamers that can identify senescent cells in humans. Aptamers with the ability to latch onto senescent cells could potentially deliver a therapy directly to those cells. Dr. Pearson notes aptamer technology is less expensive and more versatile than conventional antibodies, proteins that are typically used to differentiate cells from one another.

"This project demonstrated a novel concept," says Dr. Maher. "Future studies may extend the approach to applications related to senescent cells in human disease."

See 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:

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

The post A new tool to find hidden ‘zombie cells’ appeared first on Mayo Clinic News Network.

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

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

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

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

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

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

Benefits of immune system aging

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

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

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

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

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

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

Media contact:

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

The post Mayo Clinic researchers discover the immune system’s ‘fountain of youth’ 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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Alzheimer's disease affects nearly seven million Americans over the age of 65, or 1 in 9 people in this age group, according to the Alzheimer's Association. Symptoms such as memory loss, trouble concentrating and performing familiar tasks, and personality changes start slowly and progress. Researchers have come a long way in understanding Alzheimer's disease and Alzheimer's Disease Related Dementias (AD/ADRD). A new consensus study report, "Preventing and Treating Dementia: Research Priorities to Accelerate Progress," identifies prevention and treatment strategies for the next decade.  

"We need cutting-edge treatments to help improve the lives of patients who are suffering from debilitating symptoms of dementia and prevention for those at risk," says Nilüfer Ertekin-Taner, M.D., Ph.D., chair of the Department of Neuroscience at Mayo Clinic and leader of the Genetics of Alzheimer's Disease and Endophenotypes Laboratory at Mayo Clinic's campus in Florida. "Neurodegenerative diseases not only affect patients but also the friends and family who care for them."

Dr. Ertekin-Taner served on the select ad hoc committee of the National Academies of Sciences, Engineering, and Medicine (NASEM) which conducted a study assessing the state of research on AD/ADRD and outlined critical research priorities for treatment and prevention, as well as potential barriers to progress. The National Institutes of Health, National Institute on Aging, and National Institute of Neurological Disorders and Stroke asked NASEM to form the committee in response to a request from the U.S. Congress to accelerate research into these diseases.

Researchers looked broadly at the field, including basic to translational to clinical research; lifestyle interventions aimed at preventing and treating AD/ADRD; barriers to advancing progress in the field; and the most promising areas of research. The study looked at Alzheimer's disease, frontotemporal dementia, Lewy body dementia and other vascular causes of cognitive impairment and dementia.

The report identified 11 research priorities for further NIH-funded biomedical research, including:

• Developing better tools, including novel biomarker tests and digital assessment technologies, to monitor brain health across the life course and to screen, predict and diagnose AD/ADRD at scale.

• Implementing advances in clinical research methods and tools to generate data from real-world clinical practice settings that can inform future research.

• Identifying factors driving AD/ADRD risk in diverse populations, particularly understudied and disproportionately affected groups, to better understand disease heterogeneity — including molecular subtypes and disparities in environmental exposures — and to identify prevention opportunities and advance health research equity.

• Characterizing the exposome and gene-environment interactions across the life course to gain insights into biological mechanisms and identify opportunities to reduce AD/ADRD risk and increase resilience.

• Integrating innovative approaches and novel tools into the planning, design and execution of studies to accelerate the identification of effective interventions.

• Advancing the development and evaluation of combination therapies (including pharmacological and nonpharmacological approaches) to better address the multifactorial nature of AD/ADRD.

• Evaluating precision medicine approaches for the prevention and treatment of AD/ADRD to better identify interventions likely to benefit specific groups of individuals.

The report calls for breaking down silos for more collaborative, multidisciplinary research; fostering inclusive research to eliminate health disparities; developing innovative funding strategies; and increasing innovation in research through the expansion of public-private partnerships, among others.

"The past decade of research investments in AD/ADRD has led to significant progress in our understanding of these diseases, bringing us closer to treatments," Dr. Taner said. "In the next decade, we must maintain the momentum of research and innovation to translate these advances to cures for millions of patients and caregivers affected by the dementia epidemic."

Note: Dr. Ertekin-Taner will participate in a webinar on Jan. 15 with other committee members to discuss the report.

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Most patients with Alzheimer's disease and Alzheimer's Disease Related Dementias (ADRD) experience the gradual onset and progression of cognitive symptoms, leading to decline over years or decades. However, in a small subset of patients, symptoms begin rapidly, leading to dementia within one year and complete incapacitation within two years of symptom onset. A new study at Mayo Clinic aims to determine why patients with Alzheimer’s disease and ADRD develop this rapidly progressive dementia (RPD).

"The factors that give rise to extreme, rapidly progressive clinical traits are unknown," says Gregg Day, M.D., a neurologist and clinical researcher at Mayo Clinic in Florida. "These cases are challenging to treat in practice because there are many possible causes and diseases to consider, many tests that can be done and a clear need to coordinate evaluations rapidly."

Dr. Day will lead a team of researchers from Mayo Clinic in Florida and Rochester, Minnesota, to study the biology of RPD through a project funded by the National Institute on Aging of the National Institutes of Health (NIA/NIH).

Specifically, the research team and collaborators aim to:

• Determine the factors that make patients with Alzheimer's disease and ADRD susceptible to RPD.
• Study the contributions of amyloid and tau toxic proteins and vascular changes in the brain to rates of progression in patients with Alzheimer's disease and ADRD.
• Identify cellular pathways that contribute to rapid declines in patients with Alzheimer's disease and ADRD.

The researchers plan to collect clinical and genomic information from 120 diverse patients with rapid progressive Alzheimer's disease and ADRD over the next three years. Findings in patients with RPD, identified through Alzheimer's Disease Research Centers studies nationally, will be compared with data from participants with typical progressive Alzheimer's disease and ADRD enrolled in studies at the Alzheimer's Disease Research Center at Mayo Clinic.  

The team hopes to learn how factors such as age, sex, medical history, structural and social determinants of health, genetic variants and other brain changes may make some patients more susceptible to rapid decline. Findings will be validated through expansive protein analyses in cerebrospinal fluid from an independent group of patients with autopsy-confirmed rapid progressive Alzheimer's disease and ADRD. Results will be extended to identify biomarkers and disease-modifying targets that may improve diagnosis and treatment of patients with Alzheimer's disease and ADRD.

"This project represents a substantial investment from NIH to study patients with RPD," says Dr. Day. "We hope the results of our research will inform new approaches, diagnostic tests and treatment targets that will improve outcomes in patients with AD/ADRD. The ultimate goal is to slow down the pathologic progression of disease in these patients, independent of their rate of decline."

The research will combine Mayo Clinic's expertise in digital innovation and telemedicine to engage patients across the United States. This study will also leverage Mayo's Clinical Trials Beyond Walls program, which allows patients to complete some, if not all assessments from the comfort of their own homes or local community facilities. The decentralized clinical trials initiative is designed to remove barriers to clinical trial participation by providing digital solutions and remote services to reimagine the trial experience for all involved, including participants, investigators, study teams and clinical care providers. Decentralized research ― studies conducted outside the walls of traditional research facilities ― may use a wide range of technologies and services such as telehealth, remote monitoring, mobile phlebotomy, retail pharmacy and home healthcare.

Other Mayo Clinic researchers working on this project include:

• Christian Lachner, M.D.
• Neill Graff-Radford, M.D.
• Leonard Petrucelli, M.D., Ph.D.
• Tania Gendron, Ph.D.
• Manoj Jain, M.D.
• Owen Ross, Ph.D.
• Nilufer Ertekin-Taner, M.D., Ph.D.
• Dennis Dickson, Ph.D.
• Melissa Murray, Ph.D.
• Vijay Ramanan, M.D., Ph.D.
• David T. Jones, M.D.
• Prashanthi Vemuri, Ph.D.
• Alicia Algeciras-Schimnich, Ph.D.
• John R. Mills, Ph.D.
• Rickey Carter, Ph.D.
• Lauren Haydu, Ph.D.

The research will be made possible through NIH grant award number R01 AG089380.

Related:

Researchers identify new criteria to detect rapidly progressive dementia

Researchers find other diseases may mimic rare brain disorder linked to dementia

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The bloodstream is teeming with plasma proteins that can increase and decrease depending on what is happening in the body. As a result, these proteins can serve as valuable biomarkers for health.

Mayo Clinic researchers have found that a specific plasma protein, called IL-23R, increases with age. The finding reveals a connection between a cellular aging process, called senescence, and specific plasma proteins in the blood that increase with age and decrease in response to therapeutics targeting senescent cells. This new discovery is published in Nature Aging.

"Our research is the first to show that IL-23R is an aging biomarker linked to senescence. Since IL-23R influences many inflammatory conditions that can increase with age, our discovery opens new lines of investigation as to how circulating IL-23R may influence disease processes with age," says senior author Marissa Schafer, Ph.D.

IL-23R is known to alert immune cells to help fight infections through inflammation, the body's defense mechanism. However, when IL-23R is overactive, it can lead to tissue damage and drive the persistent inflammation that underlies conditions such as inflammatory bowel disease, multiple sclerosis and rheumatoid arthritis.

The research team measured IL-23R levels in donated blood samples of 40 men and 40 women ranging in age from 20 to 90 years old. They found that IL-23R increased in blood circulation with age among the participants. Using a preclinical model, they showed that IL-23R is linked to markers of senescence in aged organs, particularly the kidneys.

Additionally, the researchers tested five different senotherapeutics, drugs specially designed to eliminate senescent cells. All of these drugs targeted genes or proteins that are highly expressed in senescent cells. They found the senotherapeutics reduced the amount of plasma proteins including IL-23R.

"By targeting and reducing senescent cells, we can influence the systemic landscape by decreasing inflammatory mediators that are secreted in tissues and into circulation, such as IL-23R. This suggests that IL-23R is an important aging biomarker in senescence, inflammation and organ 'cross talk' that may be useful in clinical research and practice," explains lead author Chase Carver, Ph.D.

Next steps and implications

The researchers are continuing to study how circulating IL-23R is produced, how it affects inflammatory signaling throughout the body and how it drives disease states.

They are also collaborating with others to assess if other senotherapeutic approaches or exercise reduce circulating IL-23R levels in humans.

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

The post Researchers discover an aging and inflammation biomarker appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — How long a person can stand — on one leg — is a more telltale measure of aging than changes in strength or gait, according to new Mayo Clinic research. The study appears today in the journal PLOS ONE.

Good balance, muscle strength and an efficient gait contribute to people's independence and well-being as they age. How these factors change, and at what rate, can help clinicians develop programs to ensure healthy aging. Individually, people can train their balance without special equipment and work on maintaining it over time.

In this study, 40 healthy, independent people over 50 underwent walking, balance, grip strength and knee strength tests. Half of the participants were under 65; the other half were 65 and older.

In the balance tests, participants stood on force plates in different situations: on both feet with eyes open, on both feet with eyes closed, on the non-dominant leg with eyes open, and on the dominant leg with eyes open. In the one-legged tests, participants could hold the leg they weren't standing on where they wanted. The tests were 30 seconds each.

Standing on one leg — specifically the nondominant leg — showed the highest rate of decline with age.

"Balance is an important measure because, in addition to muscle strength, it requires input from vision, the vestibular system and the somatosensory systems," says Kenton Kaufman, Ph.D., senior author of the study and director of the Motion Analysis Laboratory at Mayo Clinic. "Changes in balance are noteworthy. If you have poor balance, you're at risk of falling, whether or not you're moving. Falls are a severe health risk with serious consequences."

Unintentional falls are the leading cause of injuries among adults who are 65 and older. Most falls among older adults result from a loss of balance.

In the other tests:

• Researchers used a custom-made device to measure participants' grip. For the knee strength test, participants were in a seated position and instructed to extend their knee as forcefully as possible. Both the grip and knee strength tests were on the dominant side. Grip and knee strength showed significant declines by decade but not as much as balance. Grip strength decreased at a faster rate than knee strength, making it better at predicting aging than other strength measures.
• For the gait test, participants walked back and forth on an 8-meter, level walkway at their own pace and speed. Gait parameters didn't change with age. This was not a surprising result since participants were walking at their normal pace, not their maximum pace, Dr. Kaufman says.
• There were no age-related declines in the strength tests that were specific to sex. This indicates that participants' grip and knee strength declined at a similar rate. Researchers did not identify sex differences in the gait and balance tests, which suggests that male and female subjects were equally affected by age.

Dr. Kaufman says people can take steps to train their balance. For example, by standing on one leg, you can train yourself to coordinate your muscle and vestibular responses to maintain correct balance. If you can stand on one leg for 30 seconds, you are doing well, he says.

"If you don't use it, you lose it. If you use it, you maintain it," Dr. Kaufman says. "It's easy to do. It doesn't require special equipment, and you can do it every day."

Funding for this study includes the Robert and Arlene Kogod Professorship in Geriatric Medicine and W. Hall Wendel Jr. Musculoskeletal Professorship.

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About Mayo Clinic
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Media contact:

• Rhoda Madson, Mayo Clinic Communications, newsbureau@mayo.edu

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