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.

Growing mini-organs to find new treatments for complex disease

Mayo Clinic investigators are growing three-dimensional human intestines in a dish to track disease and find new cures for complex conditions such as inflammatory bowel disease. These mini-organs function like human intestines, with the ability to process metabolites that convert food into energy on a cellular level and secrete mucus that protects against bacteria. These 3D mini-intestines in a dish, known as "organoids," provide a unique platform for studying the intricacies of the human gut.

"We think this has the potential to revolutionize the way we approach disease research. We hope to save time and resources and avoid the development of therapies that fail upon translation into patients," says Charles Howe, Ph.D., who leads the Translational Neuroimmunology Lab. "Understanding which treatments show potential for success in human organoids could dramatically accelerate the rate of new therapies for patients with unmet needs."

Brain stimulation shows promise in treating drug addiction

Physicians use neurostimulation to treat a variety of human disorders, including Parkinson's disease, tremor, obsessive-compulsive disorder and Tourette syndrome. A Mayo Clinic neurosurgeon and his colleagues believe one form of that treatment, called deep brain stimulation (DBS), is poised to solve one of the most significant public health challenges: drug addiction.

"Drug addiction is a huge, unmet medical need," says Kendall Lee, M.D., Ph.D., who has published nearly 100 journal articles on DBS along with his colleagues. Key to treating it, he says, is cutting off the pleasurable "high" that comes with the addiction — which DBS potentially can do.

A new class of AI aims to improve cancer research and treatments

Mayo Clinic researchers have invented a new class of artificial intelligence (AI) algorithms called hypothesis-driven AI, which is a significant departure from traditional AI models that learn solely from data. The researchers note that this emerging class of AI offers an innovative way to use massive datasets to help discover the complex causes of diseases, such as cancer, and improve treatment strategies.

"This fosters a new era in designing targeted and informed AI algorithms to solve scientific questions, better understand diseases and guide individualized medicine," says co-inventor Hu Li, Ph.D., a Mayo Clinic systems biology and AI researcher. "It has the potential to uncover insights missed by conventional AI."

What's lurking in your body? Mayo probes health risks of tiny plastic particles

Similar to natural elements like iron and copper, people can ingest, absorb, or even inhale microplastics and nanoplastics and their chemical additives. A landmark study published in the New England Journal of Medicine links microplastics and nanoplastics found in plaques of human blood vessels to a potential increased risk of heart attack, stroke or death.

"Plastics have made our lives more convenient and spurred many medical advances, but we must understand their impact on human health for the years to come," says Konstantinos Lazaridis, M.D., the Carlson and Nelson Endowed Executive Director for Mayo Clinic's Center for Individualized Medicine.

Mayo Clinic researchers' new tool links Alzheimer's disease types to rate of cognitive decline

Mayo Clinic researchers have discovered a series of brain changes characterized by unique clinical features and immune cell behaviors using a new corticolimbic index tool for Alzheimer's disease, a leading cause of dementia. The tool categorizes Alzheimer's disease cases into three subtypes according to the location of brain changes and continues the team's prior work, demonstrating how these changes affect people differently. Uncovering the microscopic pathology of the disease can help researchers pinpoint biomarkers that may affect future treatments and patient care.

"Our team found striking demographic and clinical differences among sex, age at symptomatic onset and rate of cognitive decline," says Melissa Murray, Ph.D., a translational neuropathologist at Mayo Clinic.

Mayo scientists explore swabs for early endometrial, ovarian cancer detection

Early detection improves treatment outcomes for endometrial and ovarian cancers, yet far too often, women are diagnosed when in advanced stages of these diseases. Unlike many other cancers, there are no standard screenings for early detection of endometrial and ovarian cancers. Mayo Clinic researchers have uncovered specific microbial signatures linked to endometrial and ovarian cancers, and they are working toward developing innovative home swab tests for women to assess their susceptibility.

"This research not only brings us closer to understanding the microbial dynamics in cancer, but also holds the potential to transform early detection and treatment strategies to positively impact women's health globally," says Marina Walther-Antonio, Ph.D., an assistant professor of surgery leading this research.

Reversing racism's toll on heart health

People who experience chronic exposure to racism may be affected by factors such as intergenerational trauma, reduced access to healthcare, differential treatment in healthcare settings and psychological distress. These negatively affect heart health and can have a cumulative effect throughout a person's life. Researchers from Mayo Clinic and the University of Minnesota published a paper which provides a new framework describing how racism affects heart health among people of color in Minnesota. The researchers are focused on reversing these disparities.

"This framework will help scientists explore and measure how chronic exposure to racism, not race, influences health outcomes," says Sean Phelan, Ph.D., a Mayo Clinic health services researcher. "This will help enable researchers to design interventions that address the root causes of these disparities and improve heart health for people of color everywhere."

Teamwork and research play a key role in Mayo Clinic's first larynx transplant

A team of six surgeons and 20 support staff combined expertise from the Department of Otolaryngology and the Department of Transplantation in an extraordinary 21-hour operation at Mayo Clinic. The team transplanted a donor larynx to a 59-year-old patient with cancer whose damaged larynx hampered his ability to talk, swallow and breathe. This groundbreaking surgery was only the third larynx transplant in the U.S., and the world's first known successful total larynx transplant performed in a patient with an active cancer as part of a clinical trial.

"All transplants are complex, but there are more tissue types and moving parts with laryngeal transplantation than other transplants," says David Lott, M.D., lead surgeon. "Mayo Clinic's team science approach made it possible for us to offer this type of transplant on a scale that was previously unattainable."

Space: A new frontier for exploring stem cell therapy

Two Mayo Clinic researchers say that stem cells grown in microgravity aboard the International Space Station have unique qualities that could one day help accelerate new biotherapies and heal complex disease. The research analysis by Abba Zubair, M.D., Ph.D., a laboratory medicine expert and medical director for the Center for Regenerative Biotherapeutics at Mayo Clinic in Florida, and Fay Abdul Ghani, Mayo Clinic research technologist, finds microgravity can strengthen the regenerative potential of cells. 

"Studying stem cells in space has uncovered cell mechanisms that would otherwise be undetected or unknown within the presence of normal gravity," says Dr. Zubair. "That discovery indicates a broader scientific value to this research, including potential clinical applications."

Mayo Clinic’s largest-ever exome study offers blueprint for biomedical breakthroughs

Mayo Clinic's Center for Individualized Medicine has achieved a significant milestone with its Tapestry study. It generated Mayo's largest-ever collection of exome data, which includes genes that code for proteins—key to understanding health and disease.  

Researchers analyzed DNA from over 100,000 participants of diverse backgrounds, providing important insights into certain genetic predispositions to support personalized and proactive medical guidance.  "The implications of the Tapestry study are monumental," says Konstantinos Lazaridis, M.D., the Carlson and Nelson Endowed Executive Director for the Center for Individualized Medicine. "As this study continues to inform and transform the practice of personalized medicine, it also sets a new standard for how large-scale medical research can be conducted in an increasingly digital and decentralized world."   

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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:

• Colette Gallagher, Mayo Clinic Communications, newsbureau@mayo.edu

The post 10 Mayo Clinic research advances in 2024, spanning stem cell therapy in space to growing mini-organs appeared first on Mayo Clinic News Network.

Rochester, Minn. — People around the globe are living longer — but not necessarily healthier — lives, according to Mayo Clinic research. A study of 183 World Health Organization (WHO) member countries found those additional years of life are increasingly fraught with disease. This research by Andre Terzic, M.D., Ph.D., and Armin Garmany documents a widening gap between lifespan and healthspan. Their paper is published in JAMA Network Open.

"The data show that gains in longevity are not matched with equivalent advances in healthy longevity. Growing older often means more years of life burdened with disease," says Dr. Terzic, senior author. "This research has important practice and policy implications by bringing attention to a growing threat to the quality of longevity and the need to close the healthspan-lifespan gap."

Dr. Terzic is the Marriott Family Director, Comprehensive Cardiac Regenerative Medicine for the Mayo Clinic Center for Regenerative Biotherapeutics and Marriott Family Professor of Cardiovascular Research at Mayo Clinic.

Lifespan-healthspan gap largest in the U.S.

Life expectancy, or lifespan, increased from 79.2 to 80.7 years in women and from 74.1 to 76.3 years in men between 2000 and 2019, according to WHO estimates. Healthspan describes the number of years a person has lived a healthy, active, disease-free life. However, the number of years those people were living in good health did not correspondingly increase. The average global gap in lifespan versus healthspan was 9.6 years in 2019, the last year of available statistics. That represents a 13% increase since 2000.

The U.S. recorded the world's highest average lifespan-healthspan divide, with Americans living 12.4 years on average with disability and sickness. This increase from 10.9 years in 2000 comes as the U.S. also reported the highest burden of chronic disease. Mental health, substance use disorders and musculoskeletal conditions were the key contributors to illness nationally.

In addition, the study found a 25% gender disparity worldwide. Across 183 surveyed countries, women experienced a 2.4-year larger gap in lifespan versus healthspan than men. Neurological, musculoskeletal, urinary and genital tract disorders contributed to extended years of poor health among women.

"The widening healthspan-lifespan gap globally points to the need for an accelerated pivot to proactive wellness-centric care systems," says Armin Garmany, first author and an M.D./Ph.D. student in Mayo Clinic Alix School of Medicine and Mayo Clinic Graduate School of Biomedical Sciences. "Identifying contributors to the gap unique to each geography can help inform healthcare interventions specific to each country and region."

Healthspan research

The Mayo Clinic research team studied statistics from the WHO Global Health Observatory. This cross-sectional study provided data on life expectancy, health-adjusted life expectancy, years lived with disease and years of life lost among member states. The healthspan-lifespan gap for each member state was calculated by subtracting health-adjusted life expectancy from life expectancy.

The research team recommends additional exploration of demographic, health and economic characteristics to better define the disease patterns that are shaping the lifespan-healthspan disparities. Funding for the paper was provided by the Marriott Family Foundation, National Institutes of Health and National Institute of General Medical Sciences.

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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

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The post The global divide between longer life and good health appeared first on Mayo Clinic News Network.

Mayo Clinic's Center for Regenerative Biotherapeutics is collaborating with the biotech firm HepaTx on an experimental therapy to regenerate tissue in patients with late-stage liver disease. This new technology takes mesenchymal stem cells from adipose (fat) tissue and coaxes them to function like hepatocyte (liver) cells. The purpose of the collaboration is to move this technology to early clinical trials and study its effect on people with liver damage from alcohol-related hepatitis.

Mesenchymal stem cells are adult stem cells that have been well studied and have been shown to be safe in humans.

Mayo Clinic brings to the collaboration expertise in regulatory affairs, clinical trials, product development and biomanufacturing. HepaTx brings a new cell technology directed toward a disease with few therapeutic options. Together they will work to advance the engineered liver cells to first-in-human safety studies.

"Our goal in working with industry is to quickly bring a pipeline of cell-based therapeutics to patients with unmet needs," says Julie Allickson, Ph.D., chief technology officer at Mayo Clinic's Center for Regenerative Biotherapeutics. "This is a very exciting opportunity to pair Mayo Clinic's know-how with a new discovery aimed at improving the health, lives and therapeutic outcomes for patients."

A new cell-based therapy for liver disease

Excessive alcohol use damages and eventually destroys liver cells, causing inflammation that can lead to abdominal pain, scarring and liver failure. Alcoholic hepatitis is one type of chronic liver disease that affects 20-40% of heavy drinkers.

In the early stage of liver disease, treatment is aimed at managing the symptoms through a combination of small molecule drugs and quitting drinking. However, in later stages, cell and tissue damage are often irreversible. People with end-stage liver disease may need an organ transplant to survive.

The engineered liver cell technology from HepaTx is so new that it has never been manufactured on a large scale for patients. That's where the Center for Regenerative Biotherapeutics process development experts come in. They develop standard operating procedures —a blueprint of sorts — for biomanufacturing in Mayo Clinic's state-of-the-art current Good Manufacturing Practice (cGMP) facilities. CGMP refers to a set of practices that ensures a new therapy meets strict quality control and quality assurance standards for medicines made from living sources such as cells.

"We engage with investigators at proof of concept. We guide the technology through process development to identify any gaps in safety that could delay regulatory approval for a clinical trial," says Dr. Allickson. "Our biomanufacturing infrastructure is based on industry best practices, which positions us well to work with outside collaborators to advance a new therapy toward market approval for patients."

Mayo Clinic will lead the early clinical trials in which patients with alcohol-related hepatitis will be infused with the engineered liver cells. The research will focus on safety and effectiveness of this cell replacement therapy in repairing late stage disease.

Working with industry collaborators that are aligned with Mayo Clinic values is a strategic priority for the Center for Regenerative Biotherapeutics.

Mayo Clinic has a financial interest in the technology referenced in this article. 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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The post A Mayo Clinic collaboration studies engineered stem cells for liver disease appeared first on Mayo Clinic News Network.

Manufacturing engineers are at the forefront of bringing new medicines derived from human sources such as cells, blood and genes to patients. They produce what are often first-of-their kind biotherapies for diseases that previously had few or no treatment options.

"The most interesting thing about our job is being able to be part of a team that brings transformative cell-based therapies to the clinic," says Kyle Ecker, advanced biomanufacturing engineer supervisor at Mayo Clinic in Florida. "It's incredibly fulfilling to understand the scientific basis of these therapies and watch them come to life by manufacturing products for individual patients."

Mayo Clinic's Center for Regenerative Biotherapeutics has 40 manufacturing engineers in Rochester and Florida. Their work makes it possible for researchers to conduct studies that require cells to be engineered on a very short timeline. In some cases, they've been able to have cells taken from patients, manufactured and returned to them in a few weeks or less. Chimeric antigen receptor (CAR-T) cell therapy for B-cell cancers and a cell-based vaccine for ovarian cancer are two examples of experimental biotherapies manufactured at Mayo Clinic.

"Our engineering teams are very dedicated to patients. They know the importance of their job, and that's to get these drugs manufactured successfully so they can be given to patients in clinical trials," says Snigdha Rai, senior director of advanced biomanufacturing in the Center for Regenerative Biotherapeutics. "Without the engineers there would be no biomanufacturing and no cell and gene therapies for patients."

Special clean room procedures

Manufacturing engineers work within a highly controlled laboratory setting or "clean room.” Clean rooms are facilities that operate according to current Good Manufacturing Practice (cGMP) regulations to ensure therapies are consistently manufactured and meet strict quality standards. These controlled environments have powerful purification systems to filter out pollutants such as dust, airborne particles, bacteria, fungus and mold that could compromise drug safety.

Adherence to strict cleanliness guidelines dictates how engineers do their job. Before stepping into a clean room, they train extensively how to operate in a cGMP facility  without triggering contamination. They perform techniques to keep everything extremely clean or sterile, using high dexterity skills such as taking the cap off a vial and putting it back on with one hand, while the other hand fills it with a chemical compound.

They dress in coveralls or a  "bunny suit" with a hood, goggles, face shield, double gloves and boot covers to block any escape of hair or skin cells. Once they've entered the clean room, their movements are slow and intentional.

"Rapid movements or quick opening of doors could trigger the sensors that monitor for microscopic particles," says Ecker. "People and materials must flow in a specific path to prevent any type of contamination. For example, we move in one direction, entering the clean room through one door while exiting through a separate door."

A blueprint for biomanufacturing

Manufacturing engineers have the pivotal role of being the first to run processes that transform a cell and gene therapy from a discovery into experimental medicine for use in human clinical trials. They strictly follow standard operating procedures — a blueprint of sorts — to mass produce a new therapy. A minimum of two engineers work together at all times to ensure all cells are processed according to regulatory and quality standards.

"The team works very closely each step of the way. We check each other's work and keep detailed records confirming that all procedures have been completed," says Qing Cindy Shao, Ph.D., lead advanced biomanufacturing engineer. "There is no room for error."

An important function of the job is identifying when a procedure doesn’t work as intended. The therapy is then sent back to the investigator and process development group to troubleshoot the issue and make appropriate changes. On-site manufacturing facilities make it possible to address the errors early and resolve them quickly. That helps minimize delays for patients.

"Our manufacturing engineers are indispensable. They work with quality control, quality assurance and process development to ensure the therapy meets the requirements and are safe for patients," says Alina Oancea, manager of cGMP manufacturing. "When the processes work as intended, it takes about two weeks to manufacture a CAR-T cell product."

Engineers' shifts in a clean room could range from three to 10 hours depending on the project they are working on. When they've completed their process for the day, they turn off the equipment, clean up the space and dispose of biowaste. Their work plays a central role in Center for Regenerative Biotherapeutics’ strategy of biomanufacturing new cell and gene biotherapies and collaborating with industry to make them available to patients around the world.

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The post Manufacturing engineers on the cusp of delivering new biotherapies appeared first on Mayo Clinic News Network.

During his medical training, Joshua Romero, M.D., often heard about regenerative medicine and how researchers were using biologics — such as cells, proteins, and even genes — in an attempt to heal damaged tissues and organs. But it wasn't until he did an elective in regenerative medicine as a resident during his intern year at Mayo Clinic School of Graduate Medical Education that he began to grasp the promise of this emerging field.

"I saw that there was a lot of new research in this area, so it was clearly an area that's still developing," he says. "And I noticed it was a niche area that not many people have expertise in. So I think that understanding this topic at a deep level could set you apart from others."

Dr. Romero's path to medicine was relatively unconventional. He grew up in Albuquerque, New Mexico, where he credits football with keeping him out of trouble. He played linebacker for the University of New Mexico and was the first in his family to go to college. "I believe if it weren’t for sports, I wouldn’t be where I am today — I’d be on a very different path," he says.

With all his exposure to athletics, he thought about being a strength and conditioning coach, and then began to consider a career in sports medicine. "I wasn't sure I could get into medical school, and I wasn't sure I could get through it. I didn’t truly believe in myself, but I still chased it regardless," he says.

Even after he excelled in medical school and landed a highly coveted residency position at Mayo Clinic in Rochester, Dr. Romero still dealt with imposter syndrome. With support from his mentors and numerous opportunities for growth, he realized he belongs at Mayo Clinic, which he now proudly calls home.

"I feel like Mayo Clinic really shaped me into being a very competent and very compassionate physician, which is what I always wanted to be," he says.

Through his elective in regenerative medicine, Dr. Romero gained a bigger picture of the prospects and challenges of this new type of medical care. "I saw that there's a lot more beyond the science — there's the manufacturing and understanding what can and cannot occur from a regulation standpoint," he says. "There are a lot of moving parts to make it possible for us to offer these therapies to patients."

Carrie Thompson, M.D., the internal medicine residency program director at Mayo Clinic School of Graduate Medical Education, says there is "a significant gap in current healthcare education when it comes to regenerative medicine" that her program aims to help fill. "Through this elective, we have trained over 100 residents, preparing them to lead the way in this rapidly evolving field," she says.

At the 2023 American Medical Society for Sports Medicine (AMSSM) Annual Meeting, Dr. Romero was one of only a few trainees selected to give an oral presentation on his research during a special pre-conference session. This work described how injections of platelet-rich plasma (PRP) — concentrated platelets derived from a patient's own blood — are a durable treatment for plantar fasciitis, improving pain and function over the long term.

Dr. Romero contributed to a chapter on PRP for a textbook specifically focused on a branch of regenerative medicine known as orthobiologics, which addresses orthopedic issues with biologic treatments. He is also helping AMSSM develop a curriculum on orthobiologics for sports medicine fellows nationwide.

Recently, Dr. Romero has developed a particular interest in a type of orthobiologic treatment known as shockwave therapy, which uses high-energy acoustic waves to promote tissue repair and regeneration. His goal is to create a shockwave clinic that provides this therapy for athletes during their competitive seasons or people who are trying to return to physical activity.

"Investing in next-generation workforce development is essential to bring these breakthrough biotherapies into clinical practice," says Saranya Wyles, M.D., Ph.D., associate director for education at the Center for Regenerative Biotherapeutics. "Mayo Clinic is proud to be at the forefront of this transformative effort."

In June, Dr. Romero completed his fellowship in sports medicine at Mayo and now is helping with the fellowship as the associate program director. He is one of the team physicians for the local community college, where he covers athletics after hours. He is frequently joined on the sidelines by medical students or residents eager to learn the tricks of the sports medicine trade.

"Whenever someone asks about electives, or wants to know if they can shadow me, I'm happy to have them," he says. "Because you never know when a few hours of your time, or a few positive words, can change someone's career trajectory."

Looking back, Dr. Romero says he feels very fortunate to have ended up where he is.

"I think Mayo Clinic enabled me to foster a passion in regenerative biotherapeutics, and also helped me achieve a position where I am contributing to the field at a national level. That all started with an elective, continued through mentorship and training, and now, as a staff member. What started as just an interest has become a big part of what I do day to day," he says.

The post Regenerative biotherapeutics trainee comes full circle appeared first on Mayo Clinic News Network.

Regenerative Medicine Minnesota (RMM) has awarded 13 grants totalling $4.3 million to support discovery, development, translation and commercialization of regenerative medicine-based innovations to improve human health in Minnesota and beyond.

The award-winning projects and awardees for 2024 are:

Clinical Trial Award:

Phase 1 Study of Intravenous Administration of Adeno-Associated Virus Gene Therapy for Individuals with Propionic Acidemia

Michael Barry, Ph.D., Mayo Clinic

Propionic acidemia (PA) is a severe metabolic disorder caused by mutations in the PCCA gene. Traditional treatments, including stringent life-long protein restrictions and liver transplants, have limited success and significant risks. This trial will evaluate the safety and preliminary efficacy of a groundbreaking gene therapy in young children, aiming to reduce metabolic crises, improve quality of life, and preserve cognitive function. The successful execution of this project will represent a significant advancement in the treatment of PA, offering hope to patients and their families.

Infrastructure Award:

Expanding Anatomic Infrastructure for Scaling Manufacturing Operations

Patrick Walsh, Anatomic Incorporated

Anatomic, a University of Minnesota start-up company based in Minnesota, develops neural tissues used in basic science and drug development. Its current flagship product, RealDRG, can be used to support development of novel non-opioid pain medications to address the ongoing, major unmet clinical need given the substantial life loss due to the opioid epidemic. This grant will support expansion of Anatomic's facilities to produce additional neural tissues that will enable researchers to understand central mechanisms of pain and amyotrophic lateral sclerosis (ALS) resulting in new therapies for these diseases.

Discovery Science Awards:

Reactivating Netrin1/DCC Signaling to Promote Optic Nerve Regeneration

Zhe Chen, Ph.D., University of Minnesota

Vision impairment that results from optic nerve damage, such as from glaucoma, poses a significant challenge to public health. To date, there are no effective therapeutics to block or reverse optic nerve degeneration, leading to irreversible vision impairment, including blindness. This project aims to identify molecular mechanisms that could be targeted therapeutically to promote regeneration of the optic nerve.

Human Microglia Model of Spinocerebellar Ataxia Type 1 (SCA1)

Marija Cvetanovic, Ph.D., University of Minnesota

Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disease with no disease modifying treatments or therapies available. Patients with SCA1 have relentlessly progressive movement and cognitive deficits and die prematurely 10 to 20 years from the disease onset. The goal of this project is to develop a human microglia (the immune cells of the brain) model of SCA1 to better understand the disease development and how mutations in the ATXN1 gene contributes to disease progression. Successful completion of this project will pave the way for future studies to develop therapies that will target and modulate microglia resulting in better treatments for patients with SCA1.

Illuminating Elusive Proteins Associated with Age-Related Macular Degeneration

John Hulleman, Ph.D., University of Minnesota

Age-related macular degeneration (AMD) is the leading cause of blindness in the industrialized world. Although variants in two genes—ARMS2/HTRA1—are the largest genetic contributor to AMD, their role in disease pathology has been challenging to study with existing methods. The goal of this project is to develop a new approach to gain insight into the pathobiology of ARMS2 and its relevance to AMD. Researchers will develop a series of stem cells that will eventually be used to identify new treatments that promote retinal health and prevent AMD-associated blindness.

A Novel Combined Allogeneic and Autologous Cell Therapy for Meniscus Tissue Repair

Daniel Saris, M.D., Ph.D., Mayo Clinic

Despite advanced surgical techniques, meniscus repair remains a significant clinical challenge due to high failure rates and chronic disability among young patients. This project aims to address this issue through a novel, one-stage cell therapy combining allogeneic adipose-derived mesenchymal stem cells and autologous meniscus cells to promote regeneration. This therapy builds on the researchers' pioneering work with a similar approach for cartilage injuries, which showed promising results in clinical trials. The anticipated outcome is a paradigm shift in meniscus injury management, significantly reducing long-term disability and improving quality of life for young patients.

Translational Research Awards:

Feasibility of Reducing Inflammation and Lung Injury to Regenerate Lung Tissue Using an Extracellular Biotherapeutic Aerosol in a Model of Acute Respiratory Distress Syndrome (ARDS)

Bryce Beverlin II, Ph.D., Quench Medical

Acute respiratory distress syndrome (ARDS) is a severe form of lung injury and a common cause of respiratory failure. Effective drug therapies that address underlying mechanisms have not been realized and ARDS remains a leading cause of death in critically ill patients. Biologic therapeutics derived from mesenchymal stem cells and exosomes are currently being evaluated as a therapeutic strategy. However, their effectiveness is limited by the ability to reach the lungs. To overcome this limitation, Quench Medical is developing a minimally invasive inhaled biologic aerosol that delivers exosome-based therapeutics directly to lung tissues. This project aims to demonstrate the efficacy of this approach in reducing inflammation from ARDS and regenerating damaged lung tissue.

Cryopreservation of Pancreatic Islets to Achieve Diabetes Cure through Transplantation

Erik Finger, M.D., Ph.D., University of Minnesota

Diabetes is a debilitating disease that has a tremendous impact on a person's health and wellbeing. Pancreatic islet transplantation offers a potential cure, yet an insufficient quantity of high-quality islets currently limits the success of this treatment. A method for cryopreserving or “banking” of islets prior to transplant can achieve the high viability, function, and clinical scalability required for human transplantation. This study will validate the function of cryopreserved islets using the novel technology cryomesh vitrification-rewarming with the goal to launch a clinical trial of vitrified islet transplants to increase accessibility of pancreatic islet transplants to cure diabetes.

Rotator Cuff Regeneration Using BMP5

Scott Riester, M.D., Ph.D., Mayo Clinic

Rotator cuff disease causes severe shoulder pain and limited arm movement. Current treatments offer temporary relief but do not regenerate damaged tendons. Preliminary studies show that injections of the biologic agent BMP5 can improve tendon strength by 30 percent. This project aims to complete pre-clinical studies to evaluate BMP5’s safety for rotator cuff treatment and has the potential to provide a new regenerative treatment option and reduce the need for surgery.

Optimized Chimeric Antigen Receptor T Cell Therapy for Colorectal Cancer

Omar Gutierrez Ruiz, Ph.D., Mayo Clinic

Colorectal cancer (CRC) is the third most common cancer in Minnesota, yet current treatments for advanced CRC have low survival rates. This project aims to develop a targeted cell therapy that enhances the killing of cancer cells and disrupts the tumor microenvironment. The researchers will further optimize this therapy in preclinical models, paving the way for a Phase I clinical trial to improve outcomes for CRC patients.

Use of Human Lung Exosomes to Prevent Ischemia/Reperfusion Injury in Lung Transplantation

Sahar Saddoughi, M.D., Ph.D., Mayo Clinic

This study aims to mitigate ischemia reperfusion injury (IRI), a major cause of primary graft dysfunction in lung transplants, by using an FDA-approved lung spheroid cell exosome (LSC-Exo) therapy. Preliminary studies show that LSC-Exo improves lung function and reduces IRI. Researchers will test LSC-Exo in a lung transplant model and in human donor lungs rejected for transplant. Their goal is to enhance lung transplant outcomes, increase the number of usable donor lungs, and improve patient survival and quality of life. Successful completion of this study will pave the way for clinical trials.

Functional Correction of Mucopolysaccharidosis Type I (Hurler Syndrome) Using Genetically Modified Autologous Memory T Cells

Nicole Shirkey-Son, Ph.D., Kommodo Therapeutics

This study aims to develop safer and more effective therapies for patients with a class of genetic diseases, called enzymopathies resulting from missing or defective enzymes. Current therapeutic approaches fail to stop disease progression and adequately replace deficient enzymes. Researchers are developing a novel cell-based therapeutic approach using genetically modified autologous memory T cells that is capable of delivering sustained enzyme replacement. In this project researchers will complete studies on efficacy, safety, dosing, and manufacturing that are critical for translating their novel cell-based therapy for MPS I. Successful completion of this project will advance this therapeutic approach into a clinical trial to improve outcomes for patients with MPS I.

Androgen Receptor Blockade to Augment Liver Regeneration

Rory Smoot, M.D., Mayo Clinic

A liver resection, or hepatectomy, is a surgical procedure to remove part of the liver. Post-hepatectomy liver failure is a major complication, with no approved treatments currently available. This project focuses on repurposing an FDA-approved drug to enhance liver regeneration, addressing a significant unmet need for patients undergoing liver resection. Researchers will assess the efficacy and safety of this approach, ensuring it does not promote tumor growth. Successful completion of these studies will pave the way for clinical trials, potentially offering a new therapeutic option to prevent or treat post-hepatectomy liver failure and significantly improve patient outcomes.

2025 Request for Proposals

For 2025 awards, RMM is calling for transformative proposals aimed at overcoming barriers that currently prevent or hinder regenerative medicine therapies from getting into patients. Key barriers to translation in regenerative medicine include availability of preclinical models and human microphysiological systems, lengthy and expensive development timelines, scalability of manufacturing processes and product consistency. RMM aims to support projects that leverage strengths in Minnesota to overcome these barriers and position the state at the forefront of regenerative medicine. Letters of Intent are due Nov. 8. Learn more at www.regenmedmn.org/apply-grant

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About Regenerative Medicine Minnesota

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

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Rochester, Minn. — Mayo Clinic is the prime site for an ARPA-H award to develop an implantable device that acts as a living pharmacy, triggering a "cell factory" in the body to treat inflammatory disease. ARPA-H, short for Advanced Research Projects Agency for Health, is an agency within the Department of Health and Human Services. It supports research for potentially transformative biomedical and health breakthroughs.

The award for up to $42.8 million for Engage Assess SecretE (EASE): A Platform for Treating Chronic Inflammation is aimed at creating a revolutionary treatment for inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. Eventually, the hope is to use it for disorders related to an overactive immune system, such as rheumatoid arthritis and psoriasis.

"I am very excited that this project has high societal impact and patient relevance. It represents a prime example of convergence science, where clinicians, biologists and engineers come together to produce a sophisticated solution to improve patient care," says Alexander Revzin, Ph.D., a biomedical engineer and scientist at Mayo Clinic who is the principal investigator for EASE.

The researchers aim to develop a bioelectric device that carries genetically engineered cells to generate monoclonal antibodies to overcome the challenges of inflammatory disease. The high-tech gadget would be implanted in an outpatient procedure.

"It's a futuristic device that encapsulates living cells in a protective membrane to ensure long-term survival. The device will also have the ability to prompt living cells to release biotherapeutic molecules, which, in this case, is monoclonal antibodies," says Suman Bose, Ph.D., a biomedical engineer at Mayo Clinic in Arizona.

Monoclonal antibodies are engineered to target specific proteins involved in the inflammatory process, helping to reduce inflammation and manage symptoms of IBD.

It takes a union of forces

The EASE project brings together a dynamic team of more than 15 investigators from Mayo Clinic in Rochester and Arizona, University of Minnesota, Case Western Reserve University, University of Texas at Dallas, University of California Davis, State University of New York Binghamton and biotech companies EnLiSense and Sersense Inc. The team includes experts in cell encapsulation, biosensing, cell engineering, wound healing/dermatology and manufacturing as well as bioelectronics. Mayo Clinic's Center for Regenerative Biotherapeutics will play a leading role in manufacturing the cells and navigating the high-tech tool through regulatory approval for early-stage clinical trials.

Addressing unmet patient needs

As many as 70,000 Americans are diagnosed with inflammatory bowel disease every year. Flare-ups can cause stomach cramps, diarrhea and rectal bleeding. With no cure, treatment is limited to easing symptoms. Standard care for IBD has been monoclonal antibody treatment over the course of a year. That requires the patient to return to the clinic every two to eight weeks for an infusion. A recent study has shown 1 in 5 patients routinely miss their dosage.

"Skipping an infusion greatly increases the chance of relapse, loss of response and drug resistance," says William Faubion Jr., M.D., the Michael S. and Mary Sue Shannon Family Director, Mayo Clinic Center for Regenerative Biotherapeutics, and a gastroenterologist-researcher for EASE. "Clearly we need better ways of providing anti-inflammatory medicine. Our research will study whether an implantable tool that delivers therapy could improve care."  

The high-tech tool will be built in the lab and tested in preclinical studies with a goal of moving rapidly toward first-in-human clinical trials within six years. For more information on ARPA-H awards, visit the ARPA-H website.

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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:

•  Susan Buckles, Mayo Clinic Communications, newsbureau@mayo.edu

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Learn about navigating regulatory pathways that advance promising biotherapies to daily patient care at RegenBio Summit: Transforming Next-Gen Biotherapeutics 2024.  Peter Marks, M.D., Ph.D., director of the Center for Biologics Evaluation and Research within the Food and Drug Administration (FDA), will deliver a keynote address about guiding the development of new cell, gene and tissue therapies. Dr. Marks leads the Center within FDA that is responsible for ensuring that biological products are safe, effective and available to those who need them.

Register now for the event that will bring together scientists, physicians, healthcare staff, entrepreneurs, students and industry members from Dec. 9 to 11 at the Ponte Vedra Inn & Club in Ponte Vedra Beach, Florida.

"FDA views cell and gene therapy products as an excellent opportunity to expedite the delivery of potentially life-saving therapies to patients with rare diseases. The promise of these technologies is enormous, putting potentially transformative treatments for many rare diseases within reach," says Dr. Marks. "The pace of the development and availability of scientific discoveries has accelerated in recent years, introducing a promising new class of medicine that did not seem possible even a short time ago."

Dr. Marks' presentation will be of value to researchers interested in commercializing discoveries, product developers, healthcare professionals, entrepreneurs and students who want to learn more about the regulatory landscape.

Programs to expedite biotherapies

Biotherapies are made from living sources such as human cells or tissues and include genetically modified cell and gene therapies. New biological therapies must meet strict regulatory guidelines that ensure product safety, identity, strength (including potency), quality and purity before they are given to participants in clinical trials.

Recognizing patient need, the FDA has introduced programs to help accelerate the development of new therapies, such as The Support for clinical Trials Advancing Rare disease Therapeutics (START) Pilot Program. This program enables frequent communication between the FDA and the sponsor of the clinical trial to discuss drug development issues such as clinical study design, control groups and fine-tuning the enrollment of clinical trial participants

The Rare Disease Endpoint Advancement Pilot Program is another example of an FDA initiative designed to promote innovation. The goal is to advance development and timely approval of drug and biologic products for rare diseases. The FDA has several additional expedited programs for eligible products that are intended to treat serious conditions. Examples include Fast Track, Breakthrough Therapy, Regenerative Medicine Advance Therapy, and Priority Review designations.

"Facilitating the development of innovative therapies to address unmet medical needs is a high priority for FDA. Our goal is to help bring new innovations and advances to patients who need them faster and more efficiently by educating sponsors and patients about the regulations to help ensure the appropriate oversight and safe development of these therapies," says Dr. Marks.

Due to unprecedented growth and innovation in cell and gene therapies, the FDA has created a new "super office." It has hired additional staff to help ensure that FDA is positioned to address the pace of the development and availability of new biologic technologies.

"The structure of the super office includes six new offices allowing a greater capacity for current and future growth while aligning teams and functions in a way that promotes efficiencies in the long term," says Dr. Marks. "This change enables the FDA to meet the challenges facing public health."

Challenges to overcome

Manufacturing challenges such as inconsistent product quality could impact the availability of some new cell and gene therapies. This is known as product variability. Another issue is lack of harmonization. As an example, cell or gene therapy products may be available internationally under different regulatory frameworks. As a result, drug identity, strength, quality and purity may differ.

"There are no uniform global standards for the evaluation and regulation of cell and gene therapy products. We believe that harmonization efforts in this area can help facilitate more efficient clinical development," says Dr. Marks. "To that end, FDA supports work toward global regulatory convergence and, ultimately, global harmonization of regulations for these products."

Learning opportunities at the RegenBio Summit

Besides the keynote address, RegenBio Summit: Transforming Next-Gen Biotherapeutics 2024 will offer sessions on gene editing, tissue engineering and entrepreneurship. Mayo Clinic will also share its blueprint for biomanufacturing early-stage therapeutics that could seamlessly be transferred to industry collaborators to bring therapies to market for broader patient access.

"Attending RegenBio Summit is a phenomenal opportunity to hear from Mayo Clinic experts and also to build industry collaborations, learn about entrepreneurial pathways, discuss standards for new therapies and train the future workforce," says Saranya Wyles, M.D., Ph.D., associate director for education in Mayo Clinic's Center for Regenerative Biotherapeutics and course director for the RegenBio Summit.

The Center for Regenerative Biotherapeutics is sponsoring the summit as part of its commitment to bringing new biologic medicines to patients and to training the future biomanufacturing workforce.

In addition to Dr. Marks, the other keynote speakers at the summit will be:

M. Peter Marinkovic, M.D., associate professor of dermatology, Stanford University, who will speak about his pioneering research in an FDA-approved topical gene therapy for autoimmune blistering diseases.

Birgit Schultes, Ph.D., senior vice president, Intellia Therapeutics Inc., who will discuss preclinical research using the CRISPR Cas-9 gene editing tool to generate cell therapies for cancer and autoimmune diseases.

The summit also will offer plenaries featuring Mayo Clinic experts, networking events and poster sessions. Visit the summit website to register and to see the list of speakers and breakout sessions.

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CAR-T cell therapy is a treatment that harnesses the power of a person's immune system to combat cancer cells. In this regenerative immunotherapy, a person's T cells, or white blood cells known as lymphocytes that are involved in the immune system response — are collected and genetically modified to produce chimeric antigen receptors or CARs. They are then infused back into the patient's blood stream, where they target and destroy cancer cells. Mayo Clinic researchers are advancing and improving CAR-T cell therapy to expand its capabilities to treat more conditions. Read more about the latest advances in CAR-T at Mayo Clinic. 

CAR-T cell researchers at Mayo Clinic optimistic about future of treating blood cancers 

While many CAR-T cell therapies use a patient's own cells, Mayo Clinic is also exploring the applications of allogeneic, or "off-the-shelf," CAR-T therapies. These are generated by healthy donors or gene-edited sources that have been genetically altered to reduce the possibility of rejection by the patient's immune system. 

"This can provide a faster turnaround time for manufacturing, expand patient access and allow patients to receive CAR-T cell therapy at the time of need," says Yi Lin, M.D., Ph.D., a hematologist and oncologist at Mayo Clinic Comprehensive Cancer Center. 

CAR-T cell therapy is usually offered as a later-stage therapy for various blood cancers, but recent research has shown it may be useful in some blood cancer cases earlier in a patient's treatment plan.

"CAR-T cell therapy in earlier lines of treatment has reported superior outcomes as compared to using it in later lines of therapy," says Rafael Fonseca, M.D., hematologist at Mayo Clinic Comprehensive Cancer Center. 

Unleashing CAR-T cell therapy to destroy solid tumors in thyroid cancer 

Mayo Clinic researchers are working to apply CAR-T cell therapy to solid tumors in thyroid cancer. CAR-T has shown promising results in blood cancers, and new research is focused on using this treatment on more types of malignancies.

"CAR-T cell therapy is unlike other therapeutics," says Saad Kenderian, M.B., Ch.B., a hematologist and cancer researcher. "Other therapies may slow down cancer. CAR-T cell therapy has shown great promise in stopping B-cell lymphomas and leukemias. Some of my patients have gone into complete remission that has lasted for years after just one treatment." 

Could CAR-T cell therapy improve kidney transplants? 

CAR-T cell therapy could provide a revolutionary approach to organ transplantation for "sensitized patients" who are hard to match and susceptible to rejection, Mayo Clinic researchers discovered. 

Their pioneering research focuses on using CAR-T cells derived from the patient's own immune system to prevent rejection of donated organs. Sensitized patients are those who have high levels of antibodies that cause their immune systems to react negatively to potential donor organs. These patients often face extended waiting periods for a transplant. 
 
Research from this proof-of-concept study is published in Kidney International. 
 
"This research is one of the first steps toward applying CAR-T cells in the field of transplantation to try to make more donor organs available for transplant and reduce the wait for patients who need a new kidney," says Tambi Jarmi, M.D., first author on the study and a transplant nephrologist at Mayo Clinic in Florida. 

Mayo Clinic scientists pioneer immunotherapy technique for autoimmune diseases

Mayo Clinic scientists have developed an immunotherapy strategy that potentially lays the groundwork for treating a spectrum of autoimmune diseases.

The new technique, detailed in a preclinical study published in Nature Biomedical Engineering, involves combining chimeric antigen receptors (CARs) with mesenchymal stromal cells (MSCs), which are found in various tissues in the body and are known for calming down the immune system, controlling inflammation and promoting immune tolerance to prevent the body's own tissues from being attacked. 

"The pioneering approach shows potential in targeting inflammatory disease sites more precisely and improving immunosuppression and healing outcomes," says Dr. Kenderian. "We're planning to study interventions that minimize the need for long-term medications for autoimmune diseases." 

Unleashing viruses aimed at killing cancer 

Mayo Clinic cancer researcher Richard Vile, Ph.D., is leading research into genetically engineered viruses aimed at unleashing a two-pronged attack on cancer. One part of this technology, known as an oncolytic virus, is designed to infect, break open and destroy cancer cells while sparing healthy tissue. Dr. Vile's preclinical studies have shown that oncolytic viruses replicated in cancer cells and cascaded to kill other diseased cells. That, in turn, triggered an immune response in which the patient's own T cells, stimulated by the virus, recognized and targeted metastasized tumors for a second wave of cancer destruction.

"Oncolytic viruses are a way to alert the immune system and mobilize it to kill cells infected with cancer," says Dr. Vile. "There's the direct killing of cancer cells with the virus, and then there's the major effect of immune activation. The immune system is incredibly well evolved to recognize infection, clear infection and kill all the cells around it that could be harboring infection." 

Dr. Vile's team is combining oncolytic viruses with CAR-T cell therapy to target solid tumors from liver cancer. This experimental approach of loading CAR-T cells with oncolytic virus is a new way to expand CAR-T cell therapy beyond treatment for blood cancers into treatment for solid tumors. 

Preparing to biomanufacture a new CAR-T cell therapy for B-cell cancers 

Mayo Clinic research has developed a new type of CAR-T cell therapy aimed at killing B-cell blood cancers that have returned and are no longer responding to treatment. This pioneering technology, designed and developed in the lab of Hong Qin, M.D., Ph.D., killed B-cell tumors grown in the laboratory and tumors implanted in mouse models. The preclinical findings are published in Cancer Immunology, Immunotherapy. 

"This study shows our experimental CAR-T cell therapy targets several blood cancers, specifically chronic lymphocytic leukemia," says Dr. Qin. "Currently there are six different CAR-T cell therapies approved for treatment of relapsed blood cancers. While the results are impressive, not everyone responds to this treatment. Our goal is to provide novel cell therapies shaped to each patient's individual need."

Dr Qin's team developed a cell therapy to target a protein known as B-cell activating factor receptor (BAFF-R) found in patients with B-cell cancers, particularly those with chronic lymphocytic leukemia. The BAFF-R protein is linked to tumor growth. The cell therapy under investigation allows the immune system to quash cancer and target tumors that have returned or have resisted available CAR-T cell therapies. 

Using a molecular scissors to improve CAR-T cell therapy 

Mayo Clinic researchers who mined the molecular foundations of cancer have uncovered a new reason CAR-T cell therapy fails in some patients. This discovery has fueled new strategies that incorporate antibodies and gene editing to improve the outcome of this breakthrough treatment.  

"This is a very exciting discovery that offers new hope of overcoming challenges of CAR-T cell therapy that many cancer patients experience," says Dr. Kenderian, a hematologist and senior author on this research, published in Nature Communications. 

"We describe for the first time a mechanism causing the resistance and failure of CAR-T cells, which lies within a protein routinely made by the engineered cells. This research puts us on a new path for improving the longevity of CAR-T cell therapy." 

The post 7 advances in CAR-T cell therapy at Mayo Clinic appeared first on Mayo Clinic News Network.