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2 days ago · DOWN TO THE ROOTS--Persistence powers Mayo Clinic's approach to adult-derived stem cell therapies

Dr. Dietz joined Mayo Clinic in 1996 and has been a driving force behind the research into medical treatments using cell-based technologies, including adult-derived stem cells known as mesenchymal stem cells.

Allan B. Dietz, Ph.D., never intended to be a scientist.

His plan was to be a farmer, just like his father, grandfather and all the other Dietzes he knew.

“I was going to be a farmer at first. Then I was going to be a veterinarian because that’s what farm kids who like science did,” Dr. Dietz says.

But the rural Iowa boy’s plans quickly changed when he lost interest in agriculture right about the time he entered the doctorate program for genetics in the College of Veterinary Medicine and Biomedical Sciences at Texas A&M University.

“I liked the science so much I decided to just do the science,” he said.

HUMBLED DAILY

Dr. Dietz joined Mayo Clinic in 1996 and has been a driving force behind the research into medical treatments using cell-based technologies, including adult-derived stem cells known as mesenchymal stem cells. Dr. Dietz is the director of the Human Cell Therapy Laboratory. The lab develops cellular therapies to treat a variety of conditions.

There are versions of the lab at all three Mayo Clinic campuses with support from the Center for Regenerative Medicine. When a physician-scientist explores if stem cells or other cellular therapies could be an option for a patient’s disease or condition, he or she works with Dr. Dietz’s team to develop the protocol and cellular product.

This readily available expert support reduces the time it takes to move research from the initial concept to the actual creation of a product that can be tested.

“This is not a solo effort,” Dr. Dietz says. “I really believe that I have the most caring, hardworking team of physicians, scientists and support staff ever assembled. I am humbled daily by the opportunity to work with them.”

Without the lab, physicians could spend years gaining the expertise in stem cells as well as necessary Food and Drug Administration approvals to move into clinical trials. With assistance from Dr. Dietz’s lab, that time can be cut significantly — to less than a year in some cases.

“Dr. Dietz provided invaluable leadership in guiding us through the very complicated path of obtaining FDA approval for our first stem cell trials. Without Dr. Dietz, these trials would not have been possible,” says neurologist Anthony J. Windebank, M.D. “He has endless enthusiasm and a very practical approach to getting things done efficiently.”

That practical approach began when Dr. Dietz was a boy.

“My ability to solve problems and my work ethic come from growing up on a farm,” Dr. Dietz says. “On a farm, you’re almost always limited in resources. So your first response to any problem is, ‘How can I solve it with the things I have?'”

FINDING A POWERFUL TOOL

At the time he was recruited to work at Mayo Clinic in Rochester, Minnesota, there was no regenerative medicine field as it is thought of today.

The laboratory’s history is rooted in transfusion medicine — the act of collecting and testing blood to be given to patients at Mayo Clinic. In the history of blood banking, researchers found it to be a powerful tool for healing. “When you differentiate blood, cut it into different pieces, such as platelets, packed red blood cells or plasma, you have more treatment options,” explains Dr. Dietz.

“The body has tissues with powerful healing properties, and we just need to figure out how to tease them out.”

Recognizing the potential, Mayo Clinic sought a scientist who could take this research to the next logical extension and explore other opportunities for treatments created from human cells.

The field was so new and unexplored that Mayo Clinic did not even know how to advertise the position, but as luck would have it, there were a few researchers in transfusion medicine who knew a scientist known for taking on challenging puzzles. That scientist was Dr. Dietz.

THE NEXT STEP

Dr. Dietz started his work on cancer vaccines with the Mayo Clinic Cancer Center, and after developing one approach, he spoke to his division leader at the time, S. Breanndan Moore, M.D., to find out what he thought his next project should be.

“Dr. Moore said, ‘Why are you asking me? You’ll know,'” Dr. Dietz recalls.

As it turns out, he did.

Dr. Dietz was inspired by a single case study reported in literature of mesenchymal stem cells dramatically reducing one patient’s inflammatory response to graft-versus-host disease, which is often fatal.

“That was all I needed as a flag to go: ‘That’s the new thing we’re going to work on!'”

What came next was a six-year odyssey to do all the background scientific work to develop these cells as a powerful drug platform. Collaborating with Dr. Windebank, who was working with patients with amyotrophic lateral sclerosis (ALS) — also known as Lou Gehrig’s disease — Dr. Dietz realized that these cells could be a “last great hope” for these patients.

A NEW INSPIRATION

But it was not until the disease hit close to home that Dr. Dietz really understood what these patients and their families were facing.

As his team worked toward a clinical trial, Dr. Dietz was called into the office of Dr. Moore.

“He was a great practical joker, so he sat me down and asked, ‘How’s that ALS trial?’ and after being reassured that it was going well, he asked, ‘Do you think I’ll be eligible for it?’ At first, I thought he was joking, but he had been diagnosed recently with ALS.”

Dr. Dietz and his team applied to do a one patient trial so that they could bring the treatment more quickly to their friend and colleague.

“He didn’t want us to do anything to compromise the integrity of what we were doing, but we framed it as fast as we possibly could,” Dr. Dietz says.

The day they got the permission to run the single-patient trial, Dr. Dietz called Dr. Moore to share the good news. It was too late.

“He had been moved to hospice that morning,” Dr. Dietz says, his voice cracking. “So, Breanndan missed it.”

Devastated by the loss of his mentor, colleague and friend in 2009, Dr. Dietz and his team continued to plug away at the problem. This radical approach to treating patients rarely found support by traditional funding sources.

A GIGANTIC UNMET NEED

While the Mayo Clinic Department of Laboratory Medicine and Pathology and the Center for Regenerative Medicine provided financial help for the Human Cell Therapy Laboratory, critical funding has come from benefactors. Dr. Dietz and the lab have done the heavy lifting needed to develop multiple cell-based treatments. This development work is amplified as this new important class of cellular drugs gets into the hands of physicians. The combination of the Human Cell Therapy Laboratory developing these drugs and clinical experts using these drugs supported by like-minded donors is a powerful combination.

“There isn’t anybody who’s not touched by one of these terrible diseases, and we started out purposely picking really tough ones like brain cancer, ALS, multiple system atrophy and wounds that won’t heal, because there is nothing else for these patients,” Dr. Dietz says. “It is a gigantic unmet need.”

And Dr. Dietz’s stubborn work ethic propels him to meet those needs for patients.

“Science is very much like a farm: an endless amount of work and a new flavor of problems every day,” Dr. Dietz says. “It is up to us to figure it out.”


THE AMAZING STEM CELL

Stem cells are “master cells” and can be “guided to become many other cell types. Here are several ways stem cells can be used in patient care.

Blood and bone marrow stem cell treatments/transplants

Healthy stem cells are injected into the body to produce new blood. Stem cells may be from the patient’s own body, a donor or from umbilical cord blood.

Regenerative cellular therapies

Stem cells have the potential to rebuild healthy tissues, potentially helping people with heart disease, ALS, diabetes, Alzheimer’s disease, cancer, Parkinson’s disease, liver disease and more.

Cells as drugs

Stem cells can be used to influence other cells. For example, stem cells can be injected into joints to reduce pain and swelling, or into soft tissue to promote healing.

Testing of new drugs for safety and effectiveness

Quality and safety of investigational drugs could be tested on stem cells that have been transformed into tissue-specific cells. Researchers can monitor for side effects in the cells from the drug before exposing a patient to it.

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Mayo Clinic is a nonprofit organization committed to clinical practice, education and research, providing expert, whole-person care to everyone who needs healing. This article was originally featured on the philanthropic site “You Are…the campaign for Mayo Clinic.”

Tue, Apr 25 8:00am · The Case for Stem Cell Treatments for ALS

When nerve cells in the brain and the spinal cord stop working normally there is a noticeable change in muscle movement and activity. Motor neurons work with the brain to control muscle movement such as gripping and walking. These activities become increasingly difficult with the onset of amyotrophic lateral sclerosis (ALS) also known as Lou Gehrig’s disease or motor neuron disease.

There is no effective treatment for ALS. According to the ALS Association, an estimated 20,000 Americans between the ages of 40 and 70 are living with the progressively paralytic disorder. It is still unknown why the symptoms begin to manifest out of the blue. The time frame from the onset of symptoms to the end of life can be as short as three years. For most, the disease is not inherited; only a small percentage of patients carry the genes that are associated with ALS.

One medical approach is to try to keep the nerve cells alive as long as possible. Researchers and clinicians at Mayo Clinic are looking at the potential of cell-based therapies to promote the healing response.

“We don’t know why nerve cells die prematurely,” says Anthony Windebank, M.D., a neurologist at Mayo Clinic. “The hope with this therapy is to protect the neurons that are there and to slow the disease course.”

One cell type derived from the patient’s fat cells, mesenchymal stromal cell (MSC), has been suggested as a possible therapy to treat ALS. MSCs are known to secrete proteins that support the growth and survival of developing and mature neurons. MSCs and cytokines (small proteins) also have a controlling influence on the immune system. Research shows that the immune system has an influence on the progression of ALS.

A novel phase I clinical trial at Mayo Clinic set out to study the safety of MSC therapy. Twenty-seven participants with ALS enrolled in the study and were treated in a MSC dose-escalation safety trial over several months. The study was led by Dr. Windebank and his fellow neurologist Nathan P. Staff, M.D., Ph.D.

The results show the safety protocol is positive and the treatment is safe at the tested dosage levels. The most common side effects were temporary low back and radicular leg pain at the highest dosage levels. There was no sign of tumor formation, which is a concern with cell-based therapies. The study, Safety of intrathecal autologous adipose-derived mesenchymal stromal cells in patients with ALS, is published online in Neurology, the journal of the American Academy of Neurology.

The Revised ALS Functional Rating Scale questionnaire was taken throughout the study along with clinical examinations. Some participants reported mild, temporary, and subjective clinical improvement lasting two months or less. These effects cannot be interpreted as a positive response to MSC treatment because the trial was not blinded or placebo controlled. Progression of the disease continued in the treated patients.

The results of the safety profile indicate that the research should go forward with a longer study to determine effectiveness, and whether earlier intervention or additional MSC treatments over a longer period of time will produce meaningful results.

“We saw enough of a signal in a subset of patients to indicate that we should go on with a longer study,” says Windebank.

Phase II

The Phase II study will treat a larger group of patients for a longer period of time with the higher dosage levels. The study will include about 60 patients. All participants will receive the treatment. The study will match patients participating in the Pooled Resource Open Access ALS Clinical Trials, PRO-ACT database. The database contains more than 8,500 ALS patients participating in clinical trials. Mayo Clinic statisticians will use the de-identified and merged data from existing public and private ALS clinical trials in the database. The statisticians will match database participants with Phase II study patients on data points such as age at onset, gender, and other factors.

The Phase II study will start mid-2017 and is planned to run for 12 months. The Phase II study is partially funded by the Judith & Jean Pape Adams Charitable Foundation, the Center for Regenerative Medicine, and a grant from Regenerative Medicine Minnesota. The study will begin incrementally while additional funding is sought through additional research grants.

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This article was original published on the Mayo Clinic Center for Regenerative Medicine’s blog.

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