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

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

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

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

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

How the smartwatch trial was designed and conducted 

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

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

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

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

Designing smarter tools for a healthy workforce

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

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

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

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

Caring for caregivers: A vision for the future

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Media contact:

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

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

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

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

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

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

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

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

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

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

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

Additional resources:

• Pushing the limits of gene therapy for osteoarthritis

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September marks the start of soybean harvest in Mankato, Minnesota, a busy time of year when farmers can't afford to be away from their fields for long. So, when Craig Smith, 66, began experiencing a burning sensation while urinating, he went to his family physician right away.

He was prescribed antibiotics, but his symptoms worsened. When Smith began to pass blood, his wife insisted that they drive straight to Mayo Clinic in Rochester — about an hour and a half away. There, Mayo Clinic physicians diagnosed him with metastatic urothelial cancer, or bladder cancer, which had spread to his spine.

Smith recalls receiving a phone call late that night from his Mayo Clinic doctor, who asked him if he wanted to just maintain his health for a few years or cure his cancer.

"I said, 'I'd like you to cure it,'" says Smith.

Seeking a bladder cancer cure

Smith's father had been a farmer, which was his dream too. But his father suggested he gain additional skills to supplement his farming income. Following his father's advice and encouragement from his high school welding teacher, Smith pursued his teaching certificate in welding. What he initially thought would be five or six years of teaching turned into a 45-year career developing welding programs at several local schools while also raising cattle and growing soybeans and corn on his 2,000-acre farm. Through his welding programs, he has trained several welders now employed by local manufacturing companies.

After his diagnosis in 2023, Smith took a hiatus from teaching and farming to focus on his cancer treatments at Mayo Clinic Health System in Mankato, which included chemotherapy, radiation and immunotherapy.

Metastatic urothelial cancer that has spread beyond the bladder usually is considered incurable and inoperable. However, Smith responded well to chemotherapy and radiation to his spine, which made his oncologist, Jacob Orme, M.D., Ph.D., and urologist, Paras Shah, M.D., consider Smith for a new, surgical approach to treatment.

Smith proceeded with the proposed surgery and had his bladder, prostate and 36 lymph nodes removed.

"In Mr. Smith's bladder, we found viable cancer cells that would have led to a relapse. Now, however, he is nearly two years from diagnosis and remains disease-free," says Dr. Shah.

Smith's positive response to treatment and surgery has spurred a clinical trial testing this aggressive approach in other bladder cancer patients. Currently, 17 participants are enrolled, and the results so far have been promising.

Advances in cancer treatment, such as immunotherapy that harnesses the body's immune system to fight cancer and the identification of biomarkers in the blood or urine that show how well a patient is responding to treatment, are helping the physicians select who will benefit most from surgery.

"The impetus for this study is to attack the cancer from multiple approaches, including treatments that cover head-to-toe and treatments that are directed right at the source tumor," says Stephen A. Boorjian, M.D., who is the David and Anne Luther Chair of Urology at Mayo Clinic and a lead proponent of the study.

"We want to remove the root of the cancer after we've burned off the leaves," adds Dr. Orme.

A team of researchers, physicians and clinical trials staff expedited the clinical trial through an accelerated pathway called a Rapid Activation Trial. It's part of a larger effort at Mayo Clinic to launch new clinical trials swiftly and effectively.

"Shortening activation timelines allows us to make a difference to more patients and their families," says Michelle Monosmith, Mayo Clinic Office of Clinical Trials operations administrator.

The study is supported by a generous donation by Ronald J. and Carol T. Beerman to Mayo Clinic and has been prioritized by Dr. Boorjian and Chair of Oncology Elisabeth Heath, M.D., to achieve more cures for men and women with bladder cancer.

"Our only goal is to help our patients live better and longer," says Dr. Orme.

That's what Smith plans to do as he continues to farm, teach and spend time with his family.

The post Farmer inspires new potential bladder cancer treatment appeared first on Mayo Clinic News Network.

For Stewart, the desire to become a scientist began at home. From a young age, she was aware of her father's diagnosis with cancer and the struggles he faced as his body became resistant to some treatments. Four years ago, when she became a predoctoral student at Mayo Clinic Graduate School of Biomedical Sciences, she chose a research project addressing blood cancers like his.

Working under the mentorship of Mayo Clinic hematologist oncologist Saad Kenderian, M.B., Ch.B., she has studied specially engineered immune cells, called chimeric antigen receptor-T cells or CAR-T cells, that are used to treat blood cancers like leukemia. She identified a signaling protein that, when neutralized, boosts the function of CAR-T cells by keeping them from reaching a state of "exhaustion." She and Dr. Kenderian's team published their findings in Nature Communications.

Stewart was delighted to learn that the journey of the new concept didn't stop there. "The approach she explored is novel, and her findings show there's a solid rationale to see whether it may help patients," says Dr. Kenderian.

'An incredible learning curve'

As the opportunity to advance the idea has emerged, Stewart has begun to learn about developing a clinical trial. "It's been an incredible learning curve," she says of taking a discovery beyond the lab space.

Close collaboration between researchers and clinicians at Mayo is what makes the steps of translation — from discovery to the clinic — happen efficiently, says Dr. Kenderian. Students like Stewart have opportunities to learn about the steps that shape clinical trials to bring new treatments to patients.

She and Dr. Kenderian met with a panel of Mayo physicians to get feedback about the design of a phase 1 clinical trial, which tests the safety of a new approach in a small cohort of patients who are interested in participating. "It was a great opportunity for me to hear how things are translated into the clinic, what questions and concerns clinicians may have, and how feasible our approach may be," she says.

"CAR-T cell therapy can be remarkable for some patients who have no other options, and the hope is to develop a more durable, lasting approach. This part of the research is still in early stages, but it's a very exciting project, and I feel lucky to be a part of it."

'Beyond what seemed possible'

Many Ph.D. students at Mayo Clinic are preparing for future careers in academia and industry. Another way they can learn about research that involves human participants is through an internship at Mayo Clinic's Office of Clinical Trials. Working with Mayo's clinical trials coordinators, students have followed a clinical trial underway and learned about designing a study that provides meaningful data and protects the rights, safety and welfare of patients who volunteer to participate.

But for some students, like Olivia Sirpilla, who is graduating in May from Mayo Clinic Graduate School of Biomedical Sciences, a long series of successful experiments in Dr. Kenderian's lab has opened the door to the next stages. Sirpilla's Ph.D. research looked at developing specially engineered stem cells from fat tissue as a treatment to calm the inflammation that occurs in immune diseases.

The team's results, published in Nature Biomedical Engineering, have set the stage for two potential clinical trials. One may be applicable to graft-versus-host-disease, an immune system complication that can occur after a stem cell transplant. The findings also may be applicable to the treatment of inflammatory bowel disease, particularly for patients who no longer respond to medications.

To design these clinical trials, Sirpilla and Dr. Kenderian are working with teams of Mayo clinicians who specialize in these disorders and their standard treatments. "I chose to come to Mayo Clinic for my Ph.D. to conduct lab research that would be highly translational," she says. "But to spend my thesis work developing a new cell therapy platform that is ready to be translated into a clinical trial is beyond what I thought possible in a Ph.D."

Research that reaches patients' daily lives  

Stephanie Zawada began her Ph.D. with an interest in computational approaches to research, but she has always strived to make advances that reach patients' daily lives.

Her thesis project aimed to help physicians assess people who have experienced a stroke and may be at risk for another.  She engaged two Ph.D. mentors who shared their expertise: Bart Demaerschalk, M.D.,  and  Bradley Erickson, M.D., Ph.D. Dr. Demaerschalk is a professor of neurology who treats patients with stroke at Mayo Clinic in Arizona and has a longstanding interest in digital health and using telemedicine to reach remote patients, and Dr. Erickson is a professor of radiology who leads artificial intelligence studies at his lab at Mayo Clinic in Minnesota.

Zawada "took a very innovative approach, exploring digital tools that may help a healthcare team continue to monitor and evaluate patients who have been discharged from the hospital but remain at risk for stroke recurrence," says Dr. Demaerschalk.

First, Zawada scoured available databases to identify attributes, including mood changes and sleep patterns, that can signal an oncoming stroke and can be captured by smartphone-based technology known as "wearables." Then she worked with her mentors and members of the Center for Digital Health to develop a pilot clinical trial with patients who volunteered to participate in a study from their homes.

Zawada designed a study that met the requirements of an institutional review board, or IRB, to address regulatory compliance. Aiming to get information from a "real-world" setting — where patients interact with app-based tools and the tools account for the range of daily activities — added logistical and mathematical complexity to the project. She worked with Dr. Demaerschalk and Mayo Clinic hospital-based stroke teams to recruit a cohort of 35 patients who gave consent to be part of the clinical trial.  

"Interacting with patients and hearing their concerns is the best way to advance useful technologies," Zawada says of designing the trial. "You want the clinical trial process to be as simple as possible for participants, and the only way to learn what tools and designs can make their lives better is to listen to them."

Her results showed that several behavioral and mood changes related to cerebrovascular disease can be captured with the use of wearable devices, even from patients going about their daily routines far from a hospital. The approach will need further investigation as a strategy to improve care and in the development of clinical trial measures, but the training to conduct a clinical trial is something that Zawada will take to the next stages of her career.

"Setting up a clinical trial is a complex process and really involves a team," says Zawada, who graduates in May and plans to continue researching wearables for patients who have other severe health conditions. "My thesis project was a multi-site collaborative effort — putting together the clinical questions, the new technology and the data analysis, the connection with patients — it's why I came to train at Mayo in the first place. As a student, I couldn't have done this project anywhere else."

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

ROCHESTER, Minn. — Aortic valve stenosis (AVS) is a significant health concern affecting over 1.5 million Americans and millions more globally. Researchers at Mayo Clinic are exploring the use of a new drug called ataciguat to manage AVS. Results from preclinical and clinical studies, published in Circulation, show that ataciguat has the potential to significantly slow disease progression. The final step to establish the drug's long-term effectiveness and safety is a phase 3 trial, and efforts to launch that pivotal trial are soon to be underway with an industry partner.

In AVS, calcium deposits build up and narrow the aortic valve, forcing the heart to work harder to move blood. The condition typically progresses over time, with symptoms like chest pain, shortness of breath and fatigue affecting people over age 65. The current standard of care — watchful waiting — often leads to reduced quality of life before the condition is severe enough for the patient to have a surgical or interventional valve replacement.

"This research represents a significant advancement in the treatment of aortic valve stenosis," says Jordan Miller, Ph.D., director of the Cardiovascular Disease and Aging Laboratory at Mayo Clinic.  "Ataciguat has the potential to substantially delay or even prevent the need for valve replacement surgery, significantly improving the lives of millions."

Dr. Miller notes that the impact extends beyond simply delaying surgery. Younger patients with aggressive disease or congenital valve defects may develop symptoms in midlife. If a patient requires valve replacement before the age of 55, there is a more than 50% likelihood they will require multiple valve replacement surgeries over their lifetime due to recalcification of the implanted valve. Ataciguat, which slowed progression of native aortic valve calcification in the clinical trial, offers the potential for a once-in-a-lifetime procedure if they can reach the age of 65. The older a patient is, the less likely the implanted valve is to calcify.

Over the past decade, Mayo Clinic's research revealed that ataciguat reactivates a pathway crucial in preventing valvular calcification and stenosis. Preclinical studies in mice showed that this drug substantially slowed disease progression even when treatment began after the disease was established.  

Clinical trials in patients with moderate AVS demonstrated that once-daily ataciguat dosing was well tolerated, with minimal side effects compared to placebo. This latest phase 2 trial in 23 patients showed a 69.8% reduction in aortic valve calcification progression at six months compared to placebo, and patients receiving ataciguat tended to maintain better heart muscle function. Crucially, the research team confirmed that — despite its profound effect on slowing valve calcification — ataciguat did not negatively impact bone formation.

This important finding is the result of a collaborative effort between Mayo Clinic, the National Institutes of Health, the University of Minnesota, and Sanofi Pharmaceuticals. The research was conducted under an innovative academic-industry partnership grant administered by the National Center for Accelerating Translational Sciences and a Minnesota Biotechnology and Genomics Partnership grant.

Mayo Clinic and Dr. Miller have a financial interest in the intellectual property referenced in this news release. Mayo Clinic will use any revenue it receives to support its not-for-profit mission in patient care, education and research.  

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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:

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

The post New drug may reduce need for aortic valve surgeries by slowing disease progression appeared first on Mayo Clinic News Network.

Billie, who has smoked most of his life, understands how using tobacco can negatively affect many aspects of a person's health. He is also a member of the Navajo Nation and has witnessed the challenges that family, friends and other members of his tribe have faced quitting tobacco. In recent years, he has watched the rising use of vaping among Navajo youth with concern. He wants to discourage young people from using tobacco except for ceremonial purposes.

"Science seeking to cure disease and transform the way we deliver healthcare requires a direct connection to the people we serve."

Annie Rusk, M.D.

Billie's experiences made him an ideal candidate to advise Dr. Rusk on her research through a Mayo Clinic program called Community Engagement (CE) Studios.

CE Studios is a consultation service that connects researchers to a group of "community experts" who represent the researcher's population of interest. These experts meet with the researcher, usually during a study's planning phase, to learn how the study is being designed, ask questions and provide feedback.

Since Mayo Clinic introduced CE Studios in 2021, Dr. Rusk has used it numerous times. She believes community input is essential for all research projects, regardless of their focus. 

"By involving people with lived experiences, we can gain valuable insights and ensure our research is relevant and impactful," says Dr. Rusk. "Even discovery science projects taking place in a lab can benefit from community perspectives."

Lived experiences provide key insights

For the CE Studios session with Dr. Rusk, Billie joined three other community experts from tribes in the Midwest, Alaska and Canada in a virtual meeting. The four community experts were there to advise Dr. Rusk on a new clinical trial.

Kory Billie, a member of the Navajo Nation from Phoenix, wants to discourage youth in his community from using tobacco, except for ceremonial purposes.

Dr. Rusk's research focuses on understanding barriers to smoking cessation among Native Americans. She felt it was important to consult with people from a variety of Indigenous communities to ensure her research aligned with their community health needs and priorities.

Billie says he enjoyed this opportunity to connect with like-minded people from similar backgrounds, and to speak with Dr. Rusk about how tobacco use was affecting communities like his. He shared his experiences with homelessness and addiction, as well as the difficulty of accessing smoking cessation resources in Indian Country.

What Dr. Rusk learned from Billie and the other community experts during the CE Studios session motivated her to make an important change to her study design.

The elements of the study that resonated best with the community experts were those geared toward developing practical behavioral health interventions. Billie and the other experts emphasized that understanding the social and cultural drivers of smoking would be key to achieving meaningful outcomes.  "You have to understand a person's environment and the way they're brought up," says Billie.

The community experts were less keen on a genetic analysis component Dr. Rusk had planned to include. They felt this aspect did not align meaningfully with community health priorities. Based on this feedback, Dr. Rusk eliminated this component from her study. 

While incorporating this kind of feedback can be challenging, Dr. Rusk says the long-term benefits are worth it for all.

"Science seeking to cure disease and transform the way we deliver healthcare requires a direct connection to the people we serve," she says.

Health is a blessing

Billie says he appreciated this chance to participate in CE Studios. He hopes that the knowledge he and the other experts shared will give Dr. Rusk the context she needs to develop a tobacco intervention that will have a lasting impact. Upon completion of the study, he looks forward to hearing from her to see the results.

Billie encourages other people to consider participating in CE Studios to help advance research to improve the health of their communities. He connects his motivation for this work to a Navajo proverb that reminds his people to live their lives with purpose: "Remember to walk in beauty. Beauty before you and beauty behind you."

If the community can improve the health of its people today, Billie says, they will pass that blessing on to future generations.

Get involved in CE Studios

A CE Studios community expert can be a person with any type of lived experience. Experts receive a small honorarium in exchange for their time. People interested in joining Mayo Clinic’s database of community experts should complete a Community Expert Enrollment Form.  

Mayo Clinic Community Engaged Research

Learn more about community outreach and engagement and community-engaged research at Mayo Clinic.

This work is supported by Mayo Clinic Center for Clinical and Translational Science and by Mayo Clinic Comprehensive Cancer Center.

The post Native community experts guide tobacco cessation research appeared first on Mayo Clinic News Network.

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

The post Mayo Clinic researchers to study causes of rapidly progressive dementia appeared first on Mayo Clinic News Network.