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At its semiannual meeting on Thursday, OMRF named The Honorable Terence Kern to its board of directors, honored long-time director David Rainbolt and named Judith James, M.D., Ph.D. its first Vice President of Clinical Affairs. Judge Kern, of Tulsa, is a Senior Judge on the U.S. District Court for the Northern District of Oklahoma. A native of Clinton, Okla., Judge Kern graduated from Oklahoma State University and subsequently from the University of Oklahoma School of Law. A former Army reserve member and attorney at the Federal Trade Commission, he practiced as an attorney in Ardmore for 24 years before being named to the federal bench in 1994. He served as Chief Judge of the Northern District for seven years and took senior status in 2010. Last month, he was inducted into the OSU Hall of Fame. Rainbolt was presented with the OMRF Board of Directors Distinguished Service Award. Rainbolt, who is Chief Executive Officer of Bancfirst, joined OMRF’s board in 1994 and has served in numerous leadership roles during his 23-year tenure as an OMRF director. “David Rainbolt has been an ardent supporter of OMRF and our mission for many years,” said Prescott. “He has been actively engaged in all aspects of board service and has provided wise counsel and leadership that have proved invaluable to the foundation.” Also at the meeting, the foundation named Judith James, M.D., Ph.D., a physician-scientist, as Vice President of Clinical Affairs. In that role, she will oversee all clinical activities at the foundation, which treats and conducts clinical research projects involving thousands of patients suffering from lupus, rheumatoid arthritis and multiple sclerosis. A native of Pond Creek, Okla., James earned her M.D. and Ph.D. degrees from the University of Oklahoma Health Sciences Center and joined OMRF’s scientific staff in 1994. An internationally acclaimed researcher, she is best known for her work in the prediction and prevention of the autoimmune disease lupus. Her research has resulted in OMRF being named a National Institutes of Health Autoimmunity Center of Excellence, one of only 10 nationwide. She is chair of OMRF’s Arthritis and Clinical Immunology Research Program and holds the Lou C. Kerr Endowed Chair in Biomedical Research. “Dr. James is regarded by her peers worldwide as a pioneer in autoimmune disease prediction and treatment,” said Prescott. “She has helped expand OMRF’s clinical capabilities and assembled a stellar team of physicians dedicated to tackling some of the most puzzling and difficult-to-treat diseases. In her new role as Vice President of Clinical Affairs, she will continue to build synergy between the clinic and the research lab, which ultimately will benefit patients.” Two other OMRF researchers received special recognition at the meeting:
Finally, OMRF presented the Edward L. and Thelma Gaylord Prize for Scientific Achievement to Holly Van Remmen, Ph.D. The award is OMRF’s highest scientific prize, and it went to Van Remmen for her research on neurodegeneration and muscle loss in aging. The award is named for the late Edward L. Gaylord, who served on OMRF’s board for 30 years, and his wife, Thelma. The Gaylords’ daughter, Christy Everest, currently serves on the foundation’s board. Van Remmen earned her Ph.D. from the University of Texas Health Sciences Center, San Antonio, where she was a faculty member until joining OMRF in 2013. At OMRF, she leads the Aging & Metabolism Research Program and holds the G.T. Blankenship Chair in Aging Research. “Dr. Van Remmen is a tremendously hard worker and has a gift for fostering collaboration,” said Arlan Richardson, Ph.D., Van Remmen’s former mentor and now a professor at the University of Oklahoma Health Sciences Center. “She has grown into a noted leader in aging research.” |
New OMRF grant to investigate rare autoimmune disease
It took less than 24 hours for Sharon Tallman to lose her vision. It took half a decade to pinpoint the reason why.
“I was at a ballgame and all of a sudden my vision was blurry; I thought it was allergy related,” said Tallman. “Then I got overheated and felt like I was going to throw up. By the next morning, I couldn’t see out of my right eye.”
Tallman’s blindness and the other symptoms that followed were caused by a condition called neuromyelitis optica, or NMO. Scientists at the Oklahoma Medical Research Foundation are trying to unravel the mysteries of this rare disease and develop tools for earlier diagnosis and better treatment options.
OMRF has received a $646,000 grant to investigate the genetic origins of the condition. The one-year grant from the National Institute of Allergy and Infectious Diseases will allow OMRF researchers Bob Axtell, Ph.D., and Christopher Lessard, Ph.D., to look at how NMO starts and investigate its similarities to other autoimmune conditions like lupus and multiple sclerosis.
Also known as Devic’s disease, NMO is an autoimmune disease, which occurs when the immune system attacks its own healthy tissues as if they were harmful invaders. In the case of NMO, the body primarily attacks the optic nerves and spinal cord, resulting in inflammation that can cause severe pain and vision loss.
Unfortunately, Tallman’s first bout of vision loss was only the beginning. She also became paralyzed from the waist down in June 2015. She slowly rehabbed from a wheelchair to a walker and then a cane before walking independently by the end of the year. In early 2016, she even went completely blind for two weeks.
“Even when things are good, I never see totally. My vision, especially in my right eye, is different every day,” said Tallman, a Claremore, Okla., resident and patient at OMRF’s Multiple Sclerosis Center of Excellence, which specializes in MS and related conditions like NMO.
MS Center Director Gabriel Pardo, M.D. diagnosed Tallman with NMO, and she comes to Oklahoma City four times per year for treatment and evaluation.
“Going blind is a horrible experience, but I have met people far worse off than me,” she said. “The work being done at OMRF is unbelievable. I trust that they are making tremendous progress, and the news of this new funding is very encouraging for people like me.”
OMRF’s MS Center clinicians work with onsite researchers who investigate the origins of the disease, and they share information back and forth.
In the lab, Axtell and Lessard are digging into NMO’s root causes to speed diagnosis and improve treatment options.
“NMO is a really uncommon, devastating disease that looks a lot like MS in terms of symptoms and clinical signs,” said Axtell. “But it’s very different from MS when it comes to treatment and how potentially destructive it can be.”
Axtell said symptoms are often more severe after an NMO attack than MS itself, and the disease can also invade regions of the brain and brain stem, which can be particularly catastrophic.
“It’s a lot more inflammatory than MS, and it can actually lead to severe disability and even death, depending on where the inflammation occurs in the brain and spinal cord,” he said. “An attack there can shut down all normal functions, like breathing.”
Currently there is no approved therapy for NMO and early diagnosis is critical to minimize life-long consequences and even death.
According to the National Multiple Sclerosis Society, approximately 4,000 people the U.S. have NMO, and it occurs 80 percent of the time in women.
“This is a very poorly understood disease, and we’re looking at genetic and immunological approaches to study it,” said Lessard. “We’re hoping to use this funding to better understand it and make some headway in learning how to treat it.”
And that hard work and the potential in these research efforts fills Tallman and other NMO patients with hope.
“The work OMRF is doing is a great example of the steps scientists are taking in the fight against NMO and diseases like it,” said Tallman. “Some day, through medical research, we can put an end to this.”
The grant, number 1R56 AI118787-01A1, from the NIAID is a part of the National Institutes of Health.
OMRF scientist receives National MS Society grant
The National Multiple Sclerosis Society has awarded OMRF scientist Robert Axtell, Ph.D., a two-year, $422,400 grant to study the interplay between two specific cell types that drive the activity and progression of multiple sclerosis.
MS is a disabling autoimmune disease where the body’s immune system attacks its own healthy tissues. The disease attacks myelin, which is the protective later that covers nerves and fibers throughout the body. These attacks damage the nervous system’s ability to carry signals to and from the brain, causing a variety of symptoms including issues with vision, muscle spasms, tremors, paralysis and more.
The grant will allow Axtell to investigate how T cells and B cells, special kinds of white blood cells that have both been implicated in driving the disease process in MS, communicate with one another.
“Think of T cells as the generals of the immune system,” said Axtell. “They’re the ones that tell other cell types in the immune system what to do. B cells, on the other hand, are antibody-producing cells. One of the key things in MS is that these antibodies are incorrectly directed against myelin and interfere with the signals the brain sends to different parts of the body.”
As part of the project, Axtell will investigate how the T cells instruct B cells to make antibodies, as well as how B cells can influence T cells in a cyclical process.
“Even with the T cells playing the role of general, they still need information before they can send out orders,” he said. “So the B cells act like scouts and let the T cells know what’s going on out on the battlefield. With that information, the T cells can hand out instructions. That’s the interplay we are really going to dig into.”
By understanding this relationship between these cells, Axtell said they can see what molecules are driving the process and either block or promote certain ones to prevent or treat disease flares or progression.
The grant has a personal connection for Axtell, as well, because his work as a postdoctoral fellow at Stanford University was funded by the National Multiple Sclerosis Society from 2008-11.
“It feels like it’s come full circle, in a way,” said Axtell, who joined OMRF’s Arthritis and Clinical Immunology Research Program in 2013.
Axtell works closely with physicians at OMRF’s Multiple Sclerosis Center of Excellence to understand why MS behaves differently than other autoimmune diseases. By combining their strengths in clinical medicine and basic research, Axtell hopes to identify and develop prognostic tests that will bring personalized clinical care for patients with MS.
“Dr. Axtell continues to show why he is a rising star in his field and at OMRF,” said OMRF Vice President of Research Paul Kincade, Ph.D. “We are enthusiastic about his research and the long-term impact his findings can have on treatments for this horrible disease.”
The grant through the MS Society is RG-1602-07722. OMRF researchers Agnieshka Agasing, Rose Ko, Ph.D., Gaurav Kumar, Ph.D., and James Quinn are contributing to the project.
Multiple Sclerosis Center celebrates five-year anniversary
Multiple sclerosis requires attention to the patient as a whole.
That comprehensive approach has been at the core of the Oklahoma Medical Research Foundation’s Multiple Sclerosis Center of Excellence since it opened its doors on March 15, 2011.
While a slew of discoveries, advancements and an ever-growing patient population have changed the scale over the past five years, the vision remains the same: to provide not only complete, but also compassionate medical care.
In order to achieve that goal, it takes a dedicated, well-rounded team.
“It’s paramount to the concept of our multidisciplinary, comprehensive approach to the management of the disease,” said MS Center Director Gabriel Pardo, M.D. “Every single one of our team members is passionate about our mission to take care of these patients individually and make a positive impact on their lives. At the same time, we are promoting and developing new ideas that will, in turn, offer benefits to the community at large.”
MS Center physicians see more than 400 patients every month. With 5,567 patient visits over the past 12 months and 2,028 unique patients seen in the past two years, this 16-person MS team is constantly hard at work to make sure each individual is taken care of in every facet.
In addition to patient care, the center is devoted to the advancement of scientific knowledge through clinical and basic research. By doing this, they are able to gain a deeper understanding of these conditions, which can improve clinical outcomes for MS patients in Oklahoma and across the country.
With patient databases and a repository of biological samples, the center is creating a shared resource that enables collaborations across the world, allowing for significant advancement in the understanding, treatment and prevention of MS.
Pardo said that of all of the achievements over the past half-decade, a few instantly come to mind.
“We’ve been involved in a multitude of clinical trials, several of which have resulted in new medications that have either already been approved and made available for treatment of MS or are in the latest stages of development,” said Pardo. “Actually one of them is going soon to the FDA for review for possible approval. I think our involvement in the development of new treatments is one of the most important of our achievements. “
Secondly, OMRF’s facility remains the only comprehensive MS center in the state that offers a multidisciplinary approach to the disease.
“This anniversary allows us to take a second to pause and look back on what we have accomplished,” said Pardo. “I’m proud to say it’s quite significant on the side of both clinical medicine and research.”
OMRF scientist discovers new multiple sclerosis biomarkers
In new research from OMRF, scientists have discovered subtle biological signs in the development of multiple sclerosis that point to the need for highly individualized treatment plans for patients suffering from the disease.
MS damages the nervous system’s ability to carry signals to and from the brain. The disease can cause a wide variety of symptoms, including problems with vision, tremors, paralysis, muscle spasms, imbalance and cognitive changes.
Working with a team of international researchers, OMRF scientist Robert Axtell, Ph.D., completed a study to identify patient responses to different MS therapies, including the popular treatment interferon-beta. The findings were published in the journal Neurology, Neuroimmunology & Neuroinflammation.
According to Axtell, the wide range of patient responses to medications is one of the biggest hurdles in treating MS, as the disease can be caused or affected by a variety of factors. Researchers measured 50 immune molecules in the blood and found that certain subsets of MS patients responded well to standard treatments while others did not.
“We looked for biomarkers that indicated the presence of disease, because they can help us identify which patients respond to specific therapies,’” said Axtell. “We collaborated with a lot of folks and received blood samples and clinical data from a sizable MS patient population. It took a lot of effort from many clinical and basic scientists to complete this study.”
By knowing which biomarkers are associated with specific reactions or responses to certain drugs, said Axtell, scientists will have a better idea of how individual patients will respond to specific types of therapy. “Our study definitely showed us that MS is not biologically the same in every patient, and that lets us know that a personalized approach is needed when it comes to treatment.”
Harald Hegen, M.D., Ph.D., of the Medical University of Innsbruck, Austria, who collaborated with Axtell on the study, believes that the research provides helpful information to guide patient treatment.
“Given the large and increasing number of disease-modifying treatments for MS, there is a strong clinical need for biomarkers that enable treatment allocation in the individual patient,” said Hegen. “In the present study we observed that MS patients can be grouped by specific patterns of immune molecules, which were predictive for response to interferon-beta therapy.”
Axtell said these results may eventually help scientists use these immune molecules as a predictive test for MS.
“We need to do many other studies to verify the molecules and refine the testing before this can be taken forward commercially,” said Axtell. “But this research lays the groundwork for developing tests for prediction of MS or patient treatment options for the disease.”
OMRF scientists Christopher Lessard, Ph.D., and Indra Adrianto, Ph.D., also contributed to the work, which was supported by grants R00NS075099 from the National Institute of Neurological Disorders and Stroke and P30GM110766 from the National Institute of General Medical Science, both a part of the National Institutes of Health.
New publication marks a first for OMRF MS collaborators
A paper published in the Journal of Immunology provided a landmark moment in translational medicine for a pair of scientists at OMRF.
The paper marks the first published collaboration between Robert Axtell, Ph.D., a research scientist, and physician Gabriel Pardo, M.D., who combine their expertise to shed new light on multiple sclerosis, which is an inflammatory, degenerative disease of the central nervous system.
The two scientists’ effort focused on understanding the mechanisms of disease in MS and why specific treatment strategies do or do not respond by targeting specific immune cells. The project has been roughly a year in the making.
“It could prove to be a watershed moment for us,” said Axtell, an assistant member in OMRF’s Arthritis and Clinical Immunology Program, who came to OMRF in 2013 from Stanford University.
Since opening its Multiple Sclerosis Center of Excellence in 2011, OMRF has set out to provide a unique opportunity for MS researchers to collaborate with clinicians to better understand and treat the disease. The clinic allows for evaluation and care of patients where physicians learn firsthand what is or is not working or what needs to be addressed.
With clinical research housed in the same location as basic research, an open line of communication forms, allowing ideas to grow. This rare setup was used to investigate patient response to a popular MS therapy by using both human samples and mouse models.
“This consummates the purpose of having a clinical component to OMRF’s operation,” said Pardo, who is the director of the MS center and treats more than 2,000 MS patients. “We have a large population of individuals with a well-characterized immune-mediated disease that feeds into the strengths of the institution in basic autoimmune research. This is the first step in many to come.”
The paper represents a milestone in OMRF’s efforts to accelerate translational medicine, a discipline that takes what Pardo refers to as a “bench-to-bedside” approach. By enabling researchers and clinicians to work closely with one another and share findings, it expedites the speed with which patients can receive new treatments.
In the new paper, Axtell and Pardo show that a particular MS medication, interferon beta, alters immune cells in a way that can help to suppress the disease and its symptoms.
Scientists do not fully understand how this specific mediation works in people suffering from MS, but Axtell said these new findings will help shed light on this question. The new information also allows clinicians at OMRF and elsewhere to look for potential markers in patient response so they can tailor treatments accordingly.
Judith James, M.D., Ph.D., leader of OMRF’s autoimmune disease research efforts, is encouraged by the findings.
“Patients in OMRF’s MS Center of Excellence have been kind enough to allow us to collect extra samples just so these types of studies can be done,” said James, who holds the Lou C. Kerr Endowed Chair in Biomedical Research. “By providing samples and their clinical information, partnered with philanthropic and National Institutes of Health financial support, we hope this will be just one of many productive collaborations to occur in multiple sclerosis clinical research.”
Ultimately, said James, “The goal is that these and related studies will help improve the lives of patients with these diseases.”
Brrrrr-ing on the cold: OMRF houses Oklahoma’s own North Pole
Oh, the weather outside is frightful. But compared to the ultra-cold freezer facility at the Oklahoma Medical Research Foundation, those freezing temperatures seem positively delightful.
With temperatures that dip as low as minus 80 degrees Celsius (minus 112 degrees Fahrenheit), OMRF’s “biorepository” houses more than 1 million biological samples gathered from research subjects over the past three decades. With 2,500 cubic feet of minus 80 storage and 7,000 cubic feet of minus 20 Celsius (minus 4 degrees Fahrenheit) space, the facility, one of the largest of its kind in the U.S., guarantees that scientists will have access to the samples for generations to come.
“This deep freeze is vital to research at OMRF,” said Joel Guthridge, Ph.D., who serves as director of the core facility where the biorepository is housed. “Whenever a scientist does large-scale DNA testing to find genes that relate to a disease like lupus or heart disease, they need samples from donors. In order to keep those samples in the best possible condition for testing, we divide them up into small quantities and keep them very, very cold.”
The samples have been collected since 1981 from patients suffering from conditions such as lupus, fibromyalgia, sarcoidosis and multiple sclerosis, as well as healthy controls. OMRF physician-scientists continue to gather samples, and they’re also seeking to expand the types of disease models included in the collection through collaborative agreements with the Stephenson Cancer Center and the University of Oklahoma Health Sciences Center.
“This is the largest facility of its kind housed at a nonprofit, and we have it right here in the heart of Oklahoma City,” said OMRF President Stephen Prescott, M.D. “It’s an invaluable resource not only to scientists in Oklahoma but to researchers everywhere.”
The majority of the construction costs for the $1.5 million facility were paid for by a grant from the National Institutes of Health. Because the integrity of the samples is so important, the biorepository has a three-layer backup, including an emergency system that uses liquid nitrogen in case of a total loss of electricity.
To enter the facility, workers must don gear worthy of an Arctic expedition: parkas, heavily insulated gloves and face shields. They cannot stay in the freezer for more than 10 minutes at a time, lest they develop frostbite, hypothermia or other health issues from the extreme cold. To ensure safety, employees rely on the buddy system.
“Two people go into the freezer while a third waits outside,” said Guthridge. “If something happens, they can press an alarm to alert us they need help. Timers also ensure no one stays inside too long.”
This sample collection has contributed to more than 200 papers and important findings from scientists, helping them to identify the genetic basis and mechanisms of diseases like lupus, Sjögren’s syndrome and multiple sclerosis.
The facility was built with one goal in mind: to provide a resource to scientists that will help them learn more about specific diseases.
“New technologies are being developed every day,” said Guthridge. “This super-cold facility keeps our samples suspended and ready for use, so we’re prepared to supply them to researchers in excellent condition and very quickly. As new research methods arise for using them, it means we’re that much closer to making discoveries that will benefit patients. And that’s very cool, indeed.”
Just how cold is OMRF’s Biorepository?
32 degrees Fahrenheit, or 0 degrees Celsius, is the freezing point of water and the point at which frostbite begins to occur with prolonged skin exposure.
-31 degrees Fahrenheit (-35 Celsius) is the coldest temperature ever recorded in Oklahoma, recorded in Nowata on Feb. 10, 2011.
-90 degrees Fahrenheit (-67.7 Celsius) is the lowest winter temperature ever recorded in permanently inhabited locations. The Russian towns Oymyakon and Verkhoyansk average minus 50-degree temperatures during the winter, and the ground in both towns is permanently frozen.
-112 degrees Fahrenheit (-80 Celsius) is as low as OMRF’s biorepository can go. The temperature is so dangerous that employees are only allowed to be inside for 10 minutes at a time even in full gear.
-128.6 degrees Fahrenheit (-89.2 Celsius) is the coldest temperature ever recorded on earth at ground level. It was taken on July 21, 1983 in Antarctica.
