Advancing the Science

Mayo Clinic Medical Science Blog – an eclectic collection of research- and research education-related stories: feature stories, mini news bites, learning opportunities, profiles and more from Mayo Clinic.

About

Member has chosen to not make this information public.

Posts (58)

Mon, Apr 15 6:00am · Culturally relevant health app shows positive impact

LaPrincess Brewer, M.D., explaining heart health to a community member, using a hands-on model.

By Jay Furst

Mobile apps are popular sources of fast and easily digested consumer health information. But can they actually help in measurable ways to make you more healthy?

According to a pilot study by Mayo Clinic researchers, they can if the content is presented in a culturally relevant, targeted and engaging way — and in this case, it helps that the mobile health, or mHealth, intervention was developed in collaboration with the people who used it, within African American faith communities.

Dr. Brewer receives a demonstration of the app from David Derby, senior innovation project manager, Mayo Clinic Kern Center for the Science of Health Care Delivery.

Members of five African American church communities in Rochester, Minn., and the Minneapolis-St. Paul metro area, helped develop the app. The researchers then enrolled 50 African American adults in a 10-week study that included podcasts and multimedia educational modules on the app. Though the study was small in size, the intervention resulted in “several objectively measured positive outcomes for cardiovascular health,” according to the study, which was published online in March in the Journal of General Internal Medicine.

“This project was unique in that we used an unconventional app to develop a community-based health intervention — and we developed our intervention in partnership with the community,” says LaPrincess Brewer, M.D., a cardiologist in Mayo Clinic’s Department of Cardiovascular Medicine.

“The power and innovation of mobile health” was evident in the community engagement and outcome from this research prototype, says Dr. Brewer, the study’s first author. Participants “found it to be fun and engaging,” as well as contributing in measurable ways to their wellness.

Putting FAITH into action

The mHealth study was part of an innovative Mayo Clinic program called Fostering African-American Improvement in Total Health (FAITH), a participatory research effort aimed at preventing heart disease in underserved communities.

According to the American Heart Association, African Americans are significantly less likely than whites to meet five or more of seven factors that affect cardiovascular health. Those factors, which the association calls Life’s Simple 7 — diet, physical activity, smoking, body mass index, blood pressure, total cholesterol and fasting glucose — were used to assess the participants’ progress.

The study was conducted from October to December 2016, with follow-up assessments 28 weeks later. The study showed improvement in the biological measures, including blood pressure and total cholesterol, with significant improvement in the composite average for all seven factors.

“Our intervention, although a research prototype, offers an innovative medium to engage African American patients beyond office-based encounters through mobile technology with an overarching goal of diminishing cardiovascular disease risk and mortality,” the report says.

The study is believed to be the first to use a mobile health app as an intervention for improved  cardiovascular health among African Americans. A randomized controlled trial is the next step for assessing the model’s effectiveness, and Dr. Brewer says the app is being refined to make it “more user-friendly and more individualized to improve health behaviors.”

The app hasn’t been made available to the public, though Dr. Brewer says, “We are hoping that the mHealth lifestyle intervention will be available from the Mayo Clinic website for download, and for faith-based organizations national and internationally to use as a part of their health promotion programming.”

App reflects community input

The research is part of Mayo Clinic’s commitment to community-based participatory research that addresses health disparities. Coordinated by the Office of Health Disparities Research, similar collaborations with faith-based communities have been undertaken in Arizona and Florida.

One of the study participants, Clarence Jones, of Minneapolis, says, “The one emotion I have observed most from the participant groups is excitement — the excitement to see a product emerge from their input, and one that reflects their community and its values.”

Jones says the experience also was an opportunity for members to interact with researchers in a nontraditional way, where “their voice is being heard and considered before decisions are made. While this may seem like a simple thing, it is often not experienced by community members working with researchers.”

Another participant, Pamela Carter, of Roseville, Minn., says the 10-week intervention “made me more conscious of my daily activities. The constant reminders make this information a little more imprinted in your mind.”

Dr. Brewer’s work is supported by a grant from the National Institutes of Health and the Mayo Clinic Women’s Health Clinic. The study also was supported by the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Center for Clinical and Translational Science, Department of Cardiovascular Medicine and Office of Health Disparities Research.

###

SAVOR, SUBSCRIBE, SHARE:  Advancing the Science

  • If you enjoyed this article, you might want to subscribe for regular updates.
  • If you want to share this story with friends, social media links are at the top of the article.
  • And if you want to see other recent stories on the blog, the index page is a great place to start.

Thu, Apr 11 6:00am · Researching the immune system to provide relief from autoimmune encephalitis

Person wearing blue lab gloves and a white coat fills a test tube using a syringe

Staff in Mayo Clinic’s Center for Multiple Sclerosis and Autoimmune Neurology are researching how the immune system can target the nervous system, and more importantly for patients, how to treat it.

Shuronda Hester had just started college and was looking forward to a new chapter in her young life when mysterious and frightening symptoms derailed her plans. Shuronda began having seizures and becoming “increasingly confused, at one point asking for her great-grandmother who passed away eight years ago,” reports First Coast News. Three trips to a hospital in Tallahassee left her without answers — or treatment.

When Shuronda’s personality began to change, her mother, Tameka Lewis, brought her to Mayo Clinic’s Florida campus. “Had she stayed in Tallahassee, with the way that her behavior was, she would have been admitted into a psych ward and not gotten the proper treatment that she actually needed,” Tameka tells the station.

In another part of the country, Denise Krivach was also looking forward to a new chapter. She’d recently retired and was making plans to build a home in Montana. But then she started forgetting things. “I couldn’t find my socks — I couldn’t find anything,” Denise, a former radiologist, tells the Rochester Post-Bulletin. “‘This isn’t me,’ that’s what I kept saying — ‘this isn’t me,'” she tells the paper. Doctors in Montana diagnosed her with early onset dementia. But Denise didn’t think the diagnosis fit. “The only thought I could hold onto was, ‘there’s something wrong, and I have to get this fixed.'” She headed to Mayo Clinic’s Rochester campus for another opinion.

At Mayo Clinic, the women learned their symptoms were caused by the same condition: autoimmune encephalitis. “It’s an autoimmune disease in which your body makes antibodies that essentially go after your brain in the same way they would fight off an infection,” Jason Siegel, M.D., a neurologist at Mayo Clinic’s Florida campus, tells First Coast News. Or, as the Post-Bulletin explains: “Krivach’s brain was under attack — by her own immune system.”

The idea that the immune system could affect the brain is a fairly new one, another Post-Bulletin story reports. But not quite so new at Mayo Clinic, where the country’s first Autoimmune Neurology Clinic was established in 2006. Today, staff at the expanded Center for Multiple Sclerosis and Autoimmune Neurology at Mayo Clinic are working to learn more about the ways the immune system can target the nervous system — and how to treat it when it does.

For Shuronda and Denise, the encephalitis diagnosis marked a turning point. They had answers and, importantly, a path for moving forward. The diagnosis gave Denise “treatment options that not only stopped her cognitive decline but reversed it,” the Post-Bulletin reports. Though she has some lingering issues, she tells the publication that she’s “so, so, so much better,” and is again thinking about building home in Montana, a dream that at one point had begun to seem out of reach.

Shuronda also responded to treatment and has been able to continue her studies. “No matter what happened or what was thrown her way, she persevered,” Shuronda’s mother tells First Coast News. “She’s determined, and she has goals. She knows what she wants.” And what she wants may lead her back to Mayo Clinic — but this time, as a nurse instead of a patient.

This article originally appeared on Mayo’s In the Loop blog. 

SAVOR, SUBSCRIBE, SHARE:  Advancing the Science

  • If you enjoyed this article, you might want to subscribe for regular updates.
  • If you want to share this story with friends, social media links are at the top of the article.
  • And if you want to see other recent stories on the blog, the index page is a great place to start.

Thu, Mar 28 6:00am · When the shoelaces fray: short telomere syndromes

Article by Barbara Toman

Image of a DNA strandUnlike gray hair, one of the most significant signs of aging is invisible to the naked eye. Deep inside cells, at the tips of thread-like chromosomes, structures known as telomeres protect chromosomes from deterioration—a bit like the way caps at the ends of shoelaces prevent fraying. Telomeres naturally shorten as people age.

But sometimes, an inherited gene mutation causes telomeres to shorten at a faster rate. Abnormal telomere shortening results in accelerated-aging syndromes that affect many parts of the body and can occur in children or adults. The severity of short telomere syndromes varies, but they increase cancer risk and can lead to organ failure and death.

With help from the Center for Individualized Medicine, Mayo Clinic uses a precision-medicine approach to manage short telomere syndromes. Mayo’s Premyeloid & Bone Failure Disorder Clinic provides diagnostic testing, multidisciplinary treatment and genetic counseling for short telomere syndromes.

Photo of Dr. Mrinal Patnaik

Mrinal Patnaik, M.B.B.S.

“Short telomere syndromes have been recognized for several decades. But diagnosis has been very difficult because it requires highly specialized testing. With the advent of precision genomics, we have the opportunity to identify and manage these disorders, for the benefit of patients,” says Mrinal Patnaik, M.B.B.S., a hematologist who directs the premyeloid disorder clinic.

Although short telomere syndromes are considered rare, Mayo Clinic sees five to seven people with the disorders a month. “We think short telomeres are much more common than has been reported, and anticipate that these new precision-medicine tools will bring a fair number of cases to light,” Dr. Patnaik says.

‘The mysterious telomere’

The 2009 Nobel Prize in medicine was awarded for discoveries about what the Nobel committee called “the mysterious telomere.” Short telomeres affect parts of the body where stem cells actively divide, including bone marrow, skin and the tissues lining the lungs and digestive tract.

“These stem cells rely on telomeres to keep their integrity. Short telomeres cause the stem cells to prematurely die,” Dr. Patnaik says.

Short telomeres can lead to scarring in the lungs and liver, narrowing of the digestive tract, bone marrow failure and immune-system deficiency. The severity of the inherited condition increases with each generation—a phenomenon known as genetic anticipation.

“Children inherit from their parents not only the genetic mutation causing short telomere syndrome but also shorter and shorter telomeres,” Dr. Patnaik says. “As a result, the syndromes tend to occur at a younger age and with more severe manifestations in each generation. Eventually the life span is highly limited.”

Initial diagnosis is a challenge because the signs and systems of short telomere syndromes are diverse. “There is a lack of awareness,” Dr. Patnaik says. “A person with lung fibrosis and failing bone marrow might see a lung specialist or a blood specialist who isn’t familiar with these multispecialty syndromes and doesn’t put the clues together.”

Mayo Clinic looks for certain signs and symptoms with unexplained causes, including:

  • Personal or family history of premature graying of hair
  • Low red blood cell, white blood cell or platelet counts
  • Thickened, stiff or scarred lung or liver tissue

If short telomere syndrome is suspected, Mayo Clinic can arrange for sophisticated testing that measures the length of telomeres in an individual’s blood cells. Once short telomeres are identified, Mayo Clinic has a genetic sequencing panel to help find the mutation causing short telomeres. If genetic sequencing doesn’t uncover a mutation, whole exome sequencing—which looks at all disease-causing genes in an individual’s DNA blueprint—can be performed.

Certain genetic mutations are known to be associated with short telomeres. But only 40 to 50 percent of people with short telomeres have one of these known mutations.

“The fact that more than half our patients with short telomeres do not have detectable gene mutations on sequencing panels indicates that we haven’t yet discovered all the mutations that affect telomere length,” Dr. Patnaik says. “There also may be nongenetic mechanisms involved—which is a Pandora’s box we haven’t even opened yet.”

Seeking new treatment options

Recent research indicates that treatment with danazol, an anabolic steroid, may slow the rate of telomere shortening, as well as improve blood counts and stabilize lung and liver disease in people with short telomeres. Laboratory experiments with gene therapies are also underway. Mayo Clinic is involved in research efforts in both these areas.

“Unfortunately, while we increasingly understand the genetics and consequences of short telomeres, much work remains to be done with regards to effective treatment modalities,” Dr. Patnaik says.

Transplantation can be an option for people who experience organ failure. However, individuals with short telomere syndrome often need multiorgan transplants: bone marrow transplantation as well as a liver or lung transplant, which makes the process extremely challenging.

“The vast majority of people with short telomere syndrome are turned down for transplant because not many centers are equipped to perform multiorgan transplantation,” Dr. Patnaik says. “Our precision genomics clinic is working with the various transplant groups within Mayo Clinic to pursue safe multiorgan transplantation for these patients. At Mayo Clinic, we have a great opportunity to use precision medicine to benefit people with short telomere syndromes.”

###

This post originally appeared on the Center for Individualized Medicine blog on Feb. 14, 2019.

Like this article? Register on Center for Individualized Medicine blog and get weekly updates on our new content.

Join the conversation

For more information on the Mayo Clinic Center for Individualized Medicine, visit our blogFacebookLinkedIn or Twitter at @MayoClinicCIM.

 

SAVOR, SUBSCRIBE, SHARE:  Advancing the Science

  • If you enjoyed this article, you might want to subscribe for regular updates.
  • If you want to share this story with friends, social media links are at the top of the article.
  • And if you want to see other recent stories on the blog, the index page is a great place to start.

Tue, Mar 26 6:00am · Buh-Bye, Breast Cancer?

Can breast cancer be prevented with a vaccine? Keith Knutson, Ph.D., Department of Immunology and director of the Discovery and Translation Labs Cancer Program at Mayo Clinic in Florida, thinks so. And he thinks it will happen during his lifetime.

In collaboration with the National Breast Treatment Coalition, Dr. Knutson has developed a vaccine that could prevent all three subtypes of the disease — estrogen receptor (ER)-positive, HER2-positive and triple-negative. The vaccine targets six proteins (HER2-neu, mammaglobin-A, MAGEA3, survivin, hTERT and MUC1) that have been found through multiple studies to overexpress in breast cancers.

The new vaccine is a fundamental shift from how vaccines traditionally prevent infectious disease. Rather than use a virus, bacteria or their components, Dr. Knutson’s vaccine immunizes against proteins that are encoded in a patient’s DNA.

“When we target an infectious disease with a vaccine, we generate immunity against the microorganism that causes the disease by attacking the foreign agent,” says Dr. Knutson. “Breast cancer isn’t caused by a microorganism. Rather, it is driven by the body’s natural proteins. Therefore, we are targeting the proteins, which hasn’t been done before in a vaccine for primary prevention. Cancer vaccines sensitize the immune system to the appearance of cancer tissue. We know from preclinical studies that targeting these molecules in animal models is safe. This is a new trajectory for how we prevent disease.”

Dr. Knutson is embarking on a yearlong phase I clinical trial with women who have been treated for
advanced metastatic breast cancer that is likely to recur. This effort is supported by the National Breast
Cancer Coalition.

“We want to involve patients who are likely to benefit from the vaccine while we make sure it performs as we think it will — generating a safe immune response,” he says. “Patients who have had advanced metastatic breast cancer have nothing to lose.”

A phase II trial, likely to begin in 2020, will focus on patients who are at high risk for breast cancer. Dr. Knutson estimates it will take five to 10 years to determine if the vaccine reduced incidence of breast cancer in the high-risk population. A phase III trial would involve 100,000 women across multiple centers.

“Look around you for a women who is about 25 today,” says Dr. Knutson. “By the time she completes her child-bearing years — around age 40 — we could conceivably have this vaccine ready to prevent her from developing breast cancer. This isn’t pie in the sky. We believe this is doable. We’re working as fast as we can. All of us on the team know women who are or have been affected by breast cancer. The only thing that could speed along our efforts is additional funding for more lab techs, regulatory staff, clinical trial experts and others.”

Preventing breast cancer recurrence

Keith Knutson, Ph.D., with team members Emilie Perkerson, a research technologist, and Geraldine Vidhy Raja, Ph.D., a research fellow.

Is it possible to prevent recurrence of breast cancer by stimulating the immune system?

Dr. Knutson thinks so. He has three vaccines in clinical trials to reduce mortality from breast cancer in the absence of a primary preventive vaccine.

“We know the immune system protects against cancer. People who have higher levels of immunity to cancer have better outcomes,” he says. “We’re working on ways to safely boost these protective responses because current drug treatments for cancer are highly toxic. Vaccines, however, are not toxic.

“If we can stimulate enough immunity to these cancers, our hope is that the immune system will take over and prevent cancer from developing or recurring.”

Triple-negative breast cancer
One of these vaccines targets triple-negative breast cancer, which accounts for 15 to 20 percent of breast cancers. Currently, patients are treated with chemotherapy for this aggressive form of cancer, but suffer from high morbidity from the toxic drugs. Cancer will recur in 30 to 40 percent of patients
who have triple-negative breast cancer.

Dr. Knutson and his team have identified an antigen on the surface of triple-negative cancer cells: folate receptor alpha. The team has developed a vaccine that generates an immune response against that protein. The drug in the vaccine has been in clinical trials for patients with triple-negative breast
and ovarian cancer since 2012.

“After these patients have completed surgery and chemotherapy, we target the regions of the folate receptor alpha protein that are abnormally expressed in triple-negative cancer,” says Dr. Knutson. “We do this by immunizing patients six times over six months. Ideally, patients will develop an immune response. Then, every six to 12 months, we will give them booster shots.

“If we can maintain levels of immunity against folate receptor alpha, we could eliminate cancer recurrence or significantly reduce it in patients who are high risk for recurrence.”

Vaccination teaches the body’s immune system T cells to recognize cancers as the enemy. Dr. Knutson says, “If tumors start to grow back, there are enough of them to outrace or beat the growth of tumor cells.”

Dr. Knutson has begun a phase II clinical trial of 280 patients across Mayo Clinic locations and seven other centers. He and his team will follow patients for two to three years, examining how quickly patients develop an immune response, what the response looks like and whether the vaccine has an effect on disease recurrence.

Whether I’m at Mayo Clinic, at home or on vacation, my vaccine work is always on my mind. Rather than get me down, these personal stories motivate me to work even harder.”
– Keith Knutson, Ph.D.

“From our phase I trial, we know the vaccine works in humans to generate an immune response,” says Dr. Knutson. “In fact, the vaccine induced immunity in 90 percent of patients involved, and the response persisted for at least 12 months. We don’t yet know if the vaccine prevents disease recurrence. This is an exciting prospect to meet a significant unmet need.”

Dr. Knutson’s work in this area is supported by a $13.3 million, five-year Breakthrough Award from the Department of Defense.

Ductal carcinoma in situ
Only about 35 percent of ductal carcinoma in situ (DCIS) lesions morph into cancer, but physicians can’t identify which lesions are potentially dangerous. So the 60,000 cases of noninvasive DCIS in the U.S. each year are treated with typical breast cancer therapies including surgery, radiation and hormone therapy.

Dr. Knutson has developed a vaccine that aims to treat DCIS patients before other therapies commence to generate a fast immune response and shrink tumors. Patients would be immunized four times per week for two weeks. If successful, the vaccine could eliminate the need for surgery, radiation therapy and long-term use of hormone therapies. Dr. Knutson’s phase I vaccine trial recently began enrolling patients. He hopes this vaccine will become part of a routine immunization schedule to prevent DCIS altogether.

Dr. Knutson’s work in this area is supported by a $3.7 million grant from the Department of Defense.

HER2-neu breast cancer
Dr. Knutson recently received funding for a phase II clinical trial for a vaccine to treat HER2-neu breast cancer, which accounts for 15 to 20 percent of breast cancers. Patients will be immunized after completing treatment with surgery and chemotherapy. The vaccine will boost patients’ immune systems, and researchers will follow them to monitor for immune response and cancer recurrence. Dr. Knutson anticipates the trial will begin enrolling its 190 patients next fall. Dr. Knutson’s work in this area is supported by an $11 million, four-year Breakthrough Award from the Department of Defense.

Preventing ovarian cancer recurrence
Dr. Knutson also has developed two vaccines to boost the immune system and prevent recurrence of ovarian cancer. In a recently completed phase I trial funded by the Mayo Clinic Cancer Center, 40 percent of ovarian cancer patients in the trial have not relapsed with three years of data. Typically, 85 percent of ovarian cancer patients relapse after treatment. The team is hoping to develop a phase II trial.

Dr. Knutson says it’s likely a secondary ovarian cancer vaccine will come to fruition in his lifetime. “While rare, ovarian cancer is deadly. It recurs so rapidly that we can test vaccine strategies relatively quickly.”

Always on my mind
The gravity and urgency of his vaccine work weighs heavily on Dr. Knutson. “One of the physician assistants who worked on my first clinical trial died from ovarian cancer. My aunt survived breast cancer. We all know women who develop and die from these cancers, so there’s no time to waste,” says Dr. Knutson. “Whether I’m at Mayo Clinic, at home or on vacation, my vaccine work is always on my mind. Rather than get me down, these personal stories motivate me to work even harder. But I’ll be happy when we don’t have to hear them anymore.”

###

This article was originally published in Mayo Clinic’s Alumni Magazine, Issue 4, 2018.

SAVOR, SUBSCRIBE, SHARE:  Advancing the Science

  • If you enjoyed this article, you might want to subscribe for regular updates.
  • If you want to share this story with friends, social media links are at the top of the article.
  • And if you want to see other recent stories on the blog, the index page is a great place to start.

Thu, Mar 14 6:00am · Opioid abuse by parents puts children at risk

By Jay Furst

Children living in homes where a parent is abusing opioids are clearly impacted, in immediate ways and in ways that may change the trajectory of their lives. Those impacts, however – including the effects on the parent-child relationship – rarely have been studied in depth.

It’s a surprising gap in research, considering that between 2009 and 2014 nearly 3 percent of children 17 and under in the U.S. lived in homes where at least one parent has a substance use disorder. With an estimated 464,000 children under the age of 2 being cared for by at least one parent with a substance use disorder, it’s a public health issue that needs to be better understood and addressed.

Mayo researchers  — ­led by Magdalena Romanowicz, M.D.  and  Kathryn Schak, M.D.  — wanted to determine what research has been done on the effects of parental opioid use. They conducted an exhaustive review of studies published over a 38-year period, from 1980 through February 2018. The results were recently published in Child and Adolescent Psychiatry and Mental Health, the official journal of the International Association for Child and Adolescent Psychiatry and Allied Professions.

Their team examined reports on just over 300 studies that reviewed effects of parental opioid addiction and its impacts, but after narrowing the criteria, only 12 had a primary focus on the parent-child relationship and on children’s outcomes.  Most of the research was dated and involved a small number of participants.

“We were very surprised by how little is known about the effects of parental opioid addiction on the parenting relationship,” says Dr. Romanowicz, a Mayo Clinic psychiatrist and lead author of the review.  “From a research point of view, we have a substantial knowledge gap that needs to be addressed.”

Based on the relevant studies, the Mayo review concludes that observations of mothers with opioid use disorders were “irritable, ambivalent and disinterested, while showing greater difficulty interpreting children’s cues, compared with the control group.” Children were observed to be more avoidant, with greater disorganized attachment, and had increased risk of emotional and behavioral issues, poor academic performance and poor social skills. Younger children were at increased risk of abuse or neglect or both, which may lead to difficulties such as substance abuse later in life, according to the Mayo review.

Even with the limited studies to date, “current evidence shows association between parental opioid addiction and poorer mother-child attachment and suboptimal child developmental and behavioral outcomes,” the Mayo report says.

Dr. Schak, a Mayo Clinic psychiatrist and senior author of the review, cautioned against reading too much into the results

“To date, there have not been many studies done on this issue. One reason for this has to do with the complexity of studying the impacts of substance abuse. Most people don’t use one substance alone. Rather, they use multiple substances such as heroin, alcohol and marijuana, for example,” she says.

Dr. Romanowicz said Mayo researchers are in the final stages of another study that analyzes associations between immediate medical complications for newborns of women who used opioids during pregnancy and the long-term consequences.

“Considering that almost half of the people struggling with opioid use disorder are women of childbearing age, such studies are very important,” she says.

###

SAVOR, SUBSCRIBE, SHARE:  Advancing the Science

  • If you enjoyed this article, you might want to subscribe for regular updates.
  • If you want to share this story with friends, social media links are at the top of the article.
  • And if you want to see other recent stories on the blog, the index page is a great place to start.

Tue, Mar 12 6:00am · Patients are helping researchers crack the code on cavernous malformations

Kayla and Kandie Nelson. Kandie didn’t know she had a medical problem until the moment she wasn’t able to speak clearly. Now Kandie and her family are helping researchers learn more about the abnormally formed blood vessels that triggered her symptoms.

Blood vessels in Kandie Nelson’s brain had become abnormally tangled and twisted around themselves. But for years, she didn’t know it. Until one day when she picked up the phone at work.

“I was working at the front desk of a hotel, and I went to answer the phone, and it came out, ‘Blah, blah, blah.’ I couldn’t talk,” she says. Numbness in her hands and feet came next. Then she fell to the ground.

After being rushed to a local hospital and undergoing a series of tests, she learned what was happening. Hidden close to the surface of Kandie’s brain was a tiny tangle of blood vessels called a cavernous malformation, which Mayo Clinic neurologist Kelly Flemming, M.D., says often take on the appearance of a “little raspberry or cluster of grapes in the brain.”

The malformations occur when capillaries divide abnormally, creating a small tangle of blood vessels. In many people, they often go undetected and unnoticed. Symptoms are rare.

“We find these accidentally,” Dr. Flemming says. “Somebody had a head trauma, and they are being scanned … Or they may have migraines, and they undergo an MRI.”

But the abnormalities do sometimes show themselves, as in Kandie’s situation. While Dr. Flemming says it’s unclear why some people develop cavernous malformations and which ones will trigger symptoms, one thing is becoming more certain. In about 2 out of 10 cases, there’s a family connection. And each affected family member usually has several cavernous malformations.

That was the case for Kandie, along with her son, Bryan, and daughter, Kayla, who also were found to be living with cavernous malformations. Bryan’s was in his spinal cord and brain stem, and Kayla’s in the temporal lobe of her brain. Fortunately, each was in a location that allowed for safe surgical removal.

Now that the malformations are gone, Kandie, Bryan and Kayla are helping doctors better understand and treat cavernous malformations.

“All three of us have donated our malformations to science,” Kandie says. “God puts you here for a reason. I believe one of my reasons is to help find a cure for this.”

Learn more about Kandie, Bryan and Kayla’s story:

This story originally appeared on Mayo Clinic News Network on January 7, 2019. 

Fri, Feb 22 2:00pm · Students swap backpacks for lab coats at upcoming 'Celebration of Research'

Rochester, Minnesota, area high school students will meet Mayo Clinic researchers and tour their laboratories at the upcoming 18th biennial Celebration of Research. The daylong conference on Tuesday, Feb. 26, enables students in grades 10–12 to learn about biomedical science and research careers.

“We are excited to welcome students from our Minnesota communities, so they have an opportunity to learn more about career paths in research and how research is the future of medicine,” says conference co-chair, Jim Maher III, Ph.D., dean of Mayo Clinic Graduate School of Biomedical Sciences. Dr. Maher is the Bernard Pollack Professor of Biochemistry and Molecular Biology.

This year’s theme will be “Fishing for Cures” — a nod to the important role of zebra fish in researching human conditions.

Read more about the celebration in the news release.

###

Thu, Feb 7 6:00am · Eva Galanis, M.D.-Bitten by the virotherapy bug

Every day more than 1,600 Americans die from cancer. Most of them have cancer that can’t be cured with traditional methods — surgery, radiation and chemotherapy. The father of Evanthia Galanis, M.D., was one of them.

He died in the late 1990s from melanoma when his daughter was a junior faculty member at Mayo Clinic.

“My father would have better treatment options today,” says Dr. Galanis, chair of the Department of Molecular Medicine at Mayo Clinic in Rochester and the Sandra J. Schulze Professor. “Research has led to the availability of very effective melanoma treatments, including immunotherapy. My father always encouraged me to be the best I could be. Every time I see a patient with cancer for whom we can’t offer good options, I think of him, and my commitment to decreasing the burden of cancer and eliminating it altogether is re-energized. I’m more determined to find answers as a result of that very difficult personal experience. I know my father’s legacy makes me a better oncologist and researcher.”

From fellow to virotherapy P.I.

Dr. Galanis’ research is focused on developing viral gene and cell therapies to treat cancer. She has been the principal investigator in multiple phase I and II gene therapy and virotherapy trials in solid tumors (ovarian cancer, glioblastoma, renal cell carcinoma, colorectal cancer, melanoma and pancreatic cancer).

She believes that ongoing trials could result in viral therapy products being approved for cancer treatment in the next several years. Many viruses are drawn to cancer cells, which grow and replicate more quickly than normal cells. Virotherapy harnesses viruses’ cancer-cell-killing ability to attack cancer cells while sparing normal cells. Mayo Clinic has explored treating cancer with gene therapies and viruses for about 25 years, making it one of the oldest cancer gene therapy and virotherapy programs in the country. Dr. Galanis was there from the start — as a hematology/oncology fellow.

“When you understand what’s wrong with a cancer cell, you can design a gene-based treatment to repair the defect or convert the abnormally behaving cell to one that behaves like normal cells,” says Dr. Galanis. “That led to my interest in gene therapy — using genetic material to treat disease — and trials to introduce genes in tumors. Today we have much better ways to deliver genetic material to cells; we also can use viruses to deliver genetic material that replicates and kills cancer cells. This is a welcome alternative to chemotherapy, which isn’t selective and can be crude for and highly toxic to patients.”

The measles virus is one of the most promising viral platforms. It has shown to be safe, generates good immune response from the tumor, and can be engineered to carry genes and retargeted to be more specific against certain types of cells. In the early 2000s, Mayo Clinic researchers delivered a weakened strain of the measles virus to laboratory mice with ovarian cancer. Their tumors shrank by 80 percent. To test that approach in humans and more quickly move ideas to the clinic, Mayo Clinic created a vector production facility — one of the only academic sites in the world capable of manufacturing clinical-grade engineered viruses for patient use.

First-in-human measles virus trials

Dr. Galanis led the first-in-human clinical trials in which 36 patients with recurrent ovarian cancer were treated with homegrown measles strains. Patients treated with higher doses of the viruses achieved a median overall survival of 27 months — more than twice as long as the expected median survival in these heavily pretreated patients who had failed multiple chemotherapy regimens. The vaccine provided remarkable results on other cancers in the lab, eliminating tumors in almost every model tested.

A five-year, three-site randomized phase II trial is now comparing measles virus treatment for ovarian cancer with the treating physician’s chemotherapy of choice. In addition to efficacy, the virotherapy is much less toxic than chemotherapy, resulting in better quality of life for patients.

More recently, Dr. Galanis led the first human trial of stem cell delivery of a cancer-killing virus. The phase I/II trial uses a small amount of a patient’s fat tissue to generate stem cells at Mayo’s Human Cellular Therapy Laboratory that are then infected with measles virus. The cells are subsequently infused back to the patient. The infected stem cells help lead the virus to tumor sites. With a grant from the National Cancer Institute, the trial recently expanded the number of patients to assess efficacy and treatment impact on survival. If the trial succeeds, the way physicians deliver viruses to cancer patients could change drastically.

Designer virus

When viruses destroy cancer cells, they release hundreds of infectious virus particles to kill the remaining tumor. The infected cells also secrete chemicals that trigger the anti-tumor immune response. This ability to kill cancer cells and recruit immune cells to join the fight makes viruses a potentially potent treatment for advanced cancers that don’t respond to other therapies.

Dr. Galanis is exploring ways to strengthen this immune response to cancer by combining the measles virus with an antibody that unleashes the immune system — a combination of virotherapy and immunotherapy. In mice with malignant brain tumors, this combination therapy significantly increased survival, leading to cures in 60 percent of the animals.

In further exploration of these encouraging results, Dr. Galanis’ laboratory has modified the measles virus to express genes that significantly enhance the immune response to the tumor, which Dr. Galanis describes as a form of vaccination against cancer. The first-ever phase I clinical trial with one of these designer viruses is about to launch in patients with metastatic breast cancer in partnership with Mayo Clinic’s Specialized Program of Research Excellence (SPORE) in breast cancer.

A new standard of care

With the first-in-human testing of the measles vaccine for ovarian cancer, first-in-human stem cell delivery of a virus and novel combination virotherapy-immunotherapy approaches under her belt, Dr. Galanis remains laser-focused on rapid translation of lab work to trials.

“Viruses represent an innovative way to treat cancer, and clinical activity is very promising,” says Dr. Galanis. “Some of the leading efforts in the world in virotherapy are happening at Mayo Clinic. We believe our trials will lead to viruses becoming incorporated to the standard of care. I’m honored to be part of a team in the Department of Molecular Medicine and the Cancer Center that can bring clinical and lab work together and move science forward to help our patients and change lives.”

###

This article was originally published in Mayo Clinic’s Alumni Magazine, Issue 4, 2018.

NOTE: The composite image is from the Mayo Clinic Viral Vector Production Laboratory.

 

SAVOR, SUBSCRIBE, SHARE:  Advancing the Science

  • If you enjoyed this article, you might want to subscribe for regular updates.
  • If you want to share this story with friends, social media links are at the top of the article.
  • And if you want to see other recent stories on the blog, the index page is a great place to start.
Contact Us · Privacy Policy