Winter 2015

WINTER 2015 | SANFORDHEALTH.ORG

More common than you know

Fetal alcohol spectrum disorders in the average American community

discoveries Winter 2015

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Message from Gene Hoyme, MD More Common Than You Know Updates from Development & Research Events Calendar

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message

from Gene Hoyme, MD It has been both a privilege and honor to serve as president of Sanford Research over the last four years. During this transformational time within the Sanford organization, we have made significant strides; including key technology and infrastructure investments, growth in federal support, and recruitment of some of the best scientists in the nation.

Sanford Health Development & Research 1305 W 18th Street PO Box 5039 Sioux Falls, SD 57117-5039 For questions or additional information email us at discoveries@sanfordhealth.org or visit us on the web at sanfordhealth.org/publications.

The progress, maturity and alignment of our research efforts with the overall health system has directly impacted the quality of patient care at Sanford. None of this would have been possible without Sanford’s culture of speed and innovation, our strong organizational values, but most of all, our accomplished team of more than 200 scientists dedicated to the work of health and healing in every way possible.

As the new chief of Genetics and Genomic Medicine, I am excited to focus more closely on a personal passion of mine, and look forward to continuing to build Sanford’s expertise and capacity in this rapidly evolving area of medicine.

Gene Hoyme, MD Chief of Genetics and Genomic Medicine and Chief Academic Officer, Sanford Health

More common than you know Fetal alcohol spectrum disorders in the average American community It’s a fairly common understanding that alcohol and pregnancy should not be combined. However, there are still many women who drink while expecting. In fact, nearly 5 percent of all American children may be affected by fetal alcohol spectrum disorders (FASD).

This staggering number comes from a recent study co-authored

by Sanford researchers Eugene

Hoyme, MD, and Amy Elliott, PhD, and published in Pediatrics, the official journal of American Academy of Pediatrics. The study, “Prevalence and characteristics of fetal alcohol spectrum disorders,” explored the incidence of FASD among first-grade students, or 6 to 7 year olds, in a representative Midwestern U.S. community, which was Sioux Falls. Students were enrolled from all the elementary

Cover: Front, Jaymi Russo, senior research associate; Back, Amy Elliott, PhD, Center for Health Outcomes and Prevention director, Gene Hoyme, MD, chief of Genetics and Genomic Medicine and chief academic officer, and Amy Baete, research manager.

schools in Sioux Falls, both public and parochial. The study is the first school-based ascertainment study to be completed as a measure of FASD prevalence in American children.

FASD are a group of conditions that can occur in the children of mothers who drank alcohol during pregnancy.

Characteristics are both physical and cognitive and can include abnormal facial features, smallerthan-average physical growth, poor coordination, learning disabilities and vision and hearing problems.

Execution and results The research team gathered data on two groups of children related to physical growth, development, dysmorphology, cognition and behavior. The first group was made up of small children who were in the 25th percentile or less in height, weight and head circumference. The second group was a randomly selected control group. The mothers of children from both groups were interviewed for maternal risk related to alcohol consumption while pregnant.

Around 2.4 to 4.8 percent of all the children studied were found to have some form of FASD based on cognitive and physical attributes. Furthermore, women who had affected children displayed higher levels of weekend binge drinking before discovering they were pregnant, sought prenatal care later and less frequently, and noted the fathers of their children were frequent drinkers.

“Previous estimates of fetal alcohol spectrum disorders put the occurrence at around 1 percent in the United States,” says Hoyme. “By actively assessing the children who were part of this study, our team was able to develop a more accurate figure for the prevalence of this disorder among the predominately middle class population of Sioux Falls and identify key risk factors that can predict it.”

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Sanford Health is the only health system in the Dakotas that offers pediatric geneticists - the front line of specialty care for children with FASD. Sanford pediatric geneticist and globally renowned researcher, Gene Hoyme, MD, has been helping children with FASD his entire career.

Helping to end the cycle With vast knowledge behind the complexities of this disorder, Sanford has been researching effective FASD prevention programs for the last several years. Jessica Hanson, PhD in Sanford Research’s Center for Health Outcomes and Prevention has led several research initiatives focused on FASD prevention, and has found solutions vary across cultures and communities. “When it comes to effective prevention strategies for communities, one size does not fit all. What’s most important is that all key community organizations and stakeholders are invested in the effort and included in planning and implementation,” says Dr. Hanson.

In November, Sanford Bemidji Medical Center (SBMC), in collaboration with Beltrami County Health and Human Services and Red Lake Family & Children’s Services, secured more than $1.6 million in grant funding from PrimeWest Health’s Community Reinvestment Grant Program.

This money will go to reducing prenatal substance abuse in Beltrami, Clearwater and Hubbard counties.

“PrimeWest Health is very excited about this project,” says Jim Przybilla, CEO of PrimeWest Health.

“We chose to fund this project because it tackles a very serious problem in the region using a welldesigned plan carried out through a partnership of key local health care and human services providers.”

In 2010, 2.87 percent of newborns at Sanford Bemidji Medical Center were placed on a 72-hour hold due to prenatal exposure to drugs and/ or alcohol. In 2013, that number increased to 6.65 percent.

“We have all had first-hand experience with the sad realities that face mothers and infants who struggle with the impacts and outcomes of substance abuse during pregnancy,” says Becky Secore, director of Beltrami County Health and Human Services. “As a region we have to collaborate to improve these statistics, but more importantly to encourage healthier pregnancies, healthier children and healthier women. No one can fix this problem alone.”

Over three years, the grant will fund a collaborative local program called Reducing Substance Abuse to Improve Pregnancy Outcomes.

The program is designed to support sobriety during pregnancy and decrease the adverse effects of prenatal exposure to drugs and alcohol. It will provide intensive case management to individuals who exhibit a high risk or past evidence of substance abuse. It will also include

Dr. Elliott leads the Center for Health Outcomes and Prevention Research at Sanford Research and is involved with national and international investigations about FASD and its consequences. Amy Baete and Jaymi Russo, research staff of the Center for Health Outcomes and Prevention Research, also contributed to the study.

the recruitment of a local substance abuse specialist medical provider.

Dr. Hoyme is internationally known for his work with FASD and also serves as chief academic officer for Sanford Health and chief of Genetics and Genomic Medicine. He has led FASD research studies in South Africa for the past 15 years and helped establish the prevalence rate in South Africa, which remains the highest documented rate in the world. In 2012, Dr. Hoyme was the recipient of the National Organization on Fetal Alcohol Syndrome (NOFAS) Excellence Award, joining the ranks of almost 40 past recipients that include Senator John McCain and the late Senator Ted Kennedy.

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Breaking Ground Sanford Imagenetics changes the definition of personalized care

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updates

Sanford Research President Gene Hoyme, MD, has been named chief of Genetics and Genomic Medicine for Sanford Health and will continue as the organization’s chief academic officer. Sanford Research Vice President and Chief Operating Officer David Pearce, PhD, will succeed Dr. Hoyme in the role of Sanford Research president.

Sanford Research New Sanford Enterprise Leaders Announced Sanford Research President Gene Hoyme, MD, has been named chief of Genetics and Genomic Medicine for Sanford Health and Sanford Research Vice President and Chief Operating Officer David Pearce, PhD will succeed Dr. Hoyme in the role of Sanford Research president.

Application of genomic or precision medicine to primary care medical practice has become one of Sanford’s major strategic initiatives. The announcement of a $125 million gift from Denny Sanford last year led to the creation of Sanford Imagenetics, setting the pace for an increased focus on genetics and family history, pharmacogenetics and genetic counseling in Sanford’s internal medicine practices.

Dr. Hoyme, an internationally known clinical geneticist, served as medical director of Sanford Imagenetics and played a critical role in the development of the initiative. In his new role, Dr. Hoyme will lead efforts to incorporate principals of genetics and genomics into population health management. He will lead the enterprise practices of clinical genetics and genetic counseling at Sanford and will work toward establishment of comprehensive enterprise genetic and genomic clinical diagnostic laboratories. Dr. Hoyme will also continue to serve as chief academic officer for Sanford, a post that encompasses oversight of all educational and academic activities of the health system.

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“Dr. Hoyme’s training, skills, administrative experience and passion will help position Sanford in becoming a national leader in precision medicine,” says Rick Adcock, Sanford Health Executive Vice President.

Previously vice president and chief operating officer of Sanford Research, Dr. Pearce will oversee research activities throughout the enterprise in his new role, including a growing clinical and translational research portfolio and developing programs in genetics and genomics research. He will continue in his role as director of the Sanford Children’s Health Research Center.

Dr. Pearce is a nationally regarded researcher. His broad perspective on

medical research and international scientific reputation will continue to propel Sanford Research into the upper echelon of health-system– based research organizations.

Congratulations to Drs. Hoyme and Pearce on their advancements and their continued dedication to the mission and vision of Sanford Health.

Sanford Imagenetics Part of International Study on Genetic Predictors of Statin Response

Genetic makeup determines how each person reacts to cholesterollowering medications, according to a new study published in Nature Communications with contributions from Sanford Health’s Russ Wilke, MD. The study is titled “Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.”

Cholesterol-lowering medications, better known as statins, are the most commonly prescribed class of drugs in the United States. Examples include Mevacor (lovastatin), Pravachol (pravastatin), Zocor (simvastatin), Lipitor (atorvastatin) and Crestor (rosuvastatin). These drugs reduce the frequency and severity of cardiovascular disease in patients at risk for heart attack and stroke.

the study through his combined roles in Sanford Imagenetics and the Genetics in Statin Therapy (GIST) Consortium.

This international consortium identified four genes that determine how well statins lower cholesterol.

The first part of the study contained data from thousands of subjects participating in Randomized Controlled Trials (RCTs) across the world. The second part brought in thousands of additional patients from other partners, including the multigenerational Framingham cohort.

One of the genes found to influence lipid-lowering response, SLCO1B1, is already used to predict statin-related side effects at some clinical centers.

The GIST results were therefore accompanied by a companion article that provides therapeutic recommendations in Nature’s Clinical Pharmacology & Therapeutics.

Wilke co-authored this companion article as well, titled “The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1 and Simvastatin-Induced Myopathy: 2014 Update.”

“Sanford Imagenetics is now in the process of evaluating the potential utility of SLCO1B1 genotyping to reduce the frequency of statin side effects in routine clinical care,” said Wilke.

Wilke has been researching the field of pharmacogenetics for nearly two decades. Prior to joining Sanford in 2013, Wilke was director of genomics and cardiovascular risk at Vanderbilt University.

3rd Annual Sanford Imagenetics Genomic Medicine Symposium Held Over 125 professionals representative of nine states convened for the 3rd Annual Sanford Imagenetics Genomic Medicine Symposium at the Sanford Center in October. Medical staff, scientists, residents and students learned from national experts about incorporating advances in genetics and genomics into clinical practice.

“This is a great tradition that we have started in convening important conversations and collaboration in the rapidly changing field of genomic

Sanford Imagenetics physician and researcher, Russ Wilke, MD, co-authored an international study on pharmacogenetics and statin response.

“Not everyone responds to cholesterol-lowering medications in the same way. Some patients see a large reduction in cholesterol levels, while others see only a small reduction,” said Wilke, an internal medicine physician at Sanford Health in Fargo. “Some patients get muscle side effects, but the large majority of patients using these medications have no side effects at all.”

The international study, of unprecedented size, looked at the proportion of patient responses to statin medications that can be attributed to genetic factors.

Wilke was one of the authors of

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Powell is the principal investigator of the study. He has a clinical research program focused on head and neck cancers in partnership with Lee’s lab at Sanford Research. Powell is also an active participant in the NCI Community Oncology Research Program.

Edith Sanford Breast Cancer Center National Genomic Oncology Advisor, James M. Ford, MD, Stanford University School of Medicine, presented at the 3rd Annual Sanford Imagenetics Genomic Medicine Symposium.

medicine. This symposia significantly enhances the ongoing physician training we have here at Sanford as part of the Imagenetics initiative,” says Gene Hoyme, MD, founder of the annual event and Sanford Health’s chief of Genetics and Genomic Medicine and chief academic officer.

Presenters included Leslie G. Biesecker, MD and Jeffery A. Schloss, PhD from the National Human Genome Research Institute, Bethesda, MD; Marc S. Williams, MD, FAAP, FACMG from Geisinger Health System, Danville, PA; Russ Wilke, MD from Sanford Medical Center and the University of North Dakota, Fargo, ND; James M. Ford, MD and Mildred K. Cho, PhD from Stanford University School of Medicine, Stanford, CA; and Kent Hoskins, MD from the University of Illinois at Chicago College of Medicine, Chicago, IL.

Head and Neck Cancer Clinical Trial is First of Several Novel Immunotherapy Studies at Sanford

Steven Powell, MD

John Lee, MD

A drug that has the potential to use the body’s immune system to attack tumors is the focus 8 | discoveries

of several upcoming cancer trials at Sanford Health.

The clinical studies will determine if a PD-1 inhibitor can use the body’s immune system to clear cancers by blocking a protein that would otherwise allow cancerous cells to avoid detection. Sanford Health is one of the first approved sites in the region to offer these immunotherapy trials.

Sanford oncologist Steven Powell, MD, and otolaryngologist John Lee, MD, are currently enrolling patients with recurrent or metastatic head and neck cancers from across the Midwest.

“These trials have the potential of using the underlying mechanisms of the body’s immune system to fight the disease,” said Lee. Head and neck cancers occur in the oral cavity, throat, larynx (voice box), sinuses, nasal cavity and salivary glands. Patients are eligible for enrollment if they have a confirmed recurrent case of head or neck cancer that is considered incurable by standard therapies.

“There hasn’t been a breakthrough in head and neck cancer for years, so the final outcome of this trial will be exciting to see. Normally, patients would have to travel across the country to have access to a treatment option like this. We are delighted to offer it closer to home,” said Powell.

Additional upcoming immunotherapy trials at Sanford Health will focus on lung and gastric cancers.

Lee is a sub-investigator in the trial. His Sanford Research lab focuses on the link between HPV and the development of head and neck cancers. Last year, Lee was featured as a keynote speaker at the American Society of Clinical Oncology Annual Meeting in Chicago where he presented his pre-clinical research using PD-1 inhibitors to treat head and neck cancer.

NIH Grant to Fund Heart Disease Prevention Research at Sanford Michelle Baack, MD

Sanford Health physician and scientist Michelle Baack, MD, has been awarded a grant totaling nearly $600,000 from the National Institutes of Health (NIH) for research focused on preventing cardiovascular disease in the offspring of diabetic mothers.

Baack’s five-year project, “Lipotoxic effects of maternal diabetes and high fat diet on the developing heart,” was awarded under the NIH’s Eunice Kennedy Shriver National Institute of Child Health & Human Development.

According to Baack, certain babies are born with a deficiency of good fats or an excess of bad fats. Infants born to mothers who have diabetes during pregnancy, for example, have a deficiency of omega-3 fatty acids important for heart health.

Current treatment for diabetes during pregnancy focuses on the regulation of blood sugar levels.

However, diabetes also changes the levels of circulating fats transported from mother to the developing baby.

Exposure to abnormal circulating fats before birth may put these

babies at a higher risk for heart disease at birth and throughout life.

Baack will use a rodent model to further determine the role lipids play in the development of heart disease in offspring born to diabetic mothers.

Previous research by Baack’s lab discovered that rats born to diabetic mothers died more frequently of heart disease when their mothers ate a high-fat diet. Her study will aim to answer why those rats experienced a high mortality rate.

Furthermore, by understanding the consequences of a high-fat diet during pregnancy, Baack hopes to identify preventative strategies and improve long-term outcomes of infants who are at high risk for heart disease.

“We believe that when the developing heart is exposed to excess fat, it is forced to reprogram itself to metabolize this fat,” said Baack.

“Because the neonatal heart is not designed for such metabolism, the reprogramming could contribute to ongoing cardiac risk throughout life.

While much research has focused on the role of glucose in the development of heart disease of infants with diabetic mothers, the impact of lipids is not well recognized.”

Baack is a neonatologist at the Sanford Children’s Specialty Clinic and also runs a lab in the Children’s Health Research Center at Sanford Research. Her lab focuses on the importance of different fats (good and bad fatty acids) needed to promote normal growth, brain development and vascular health during early development.

included Trinity Christian, Grant Deuel, Canton, Spencer, AlcesterHudson, Vermillion, Sioux Falls Christian, Dell Rapids, Brandon Valley, West Central, Rutland, Sioux Valley, Chamberlain and Northeast Technical.

Sanford Study Replicates Genetic Mutations in Disease David Pearce, PhD

Sanford Research’s David Pearce, PhD, has developed a mouse model that replicates the genetic mutations in Batten disease and could lead to therapeutic approaches to treat the rare disease and other genetic disorders.

Pearce’s findings were published in a September issue of Human Molecular Genetics. “The novel Cln1R151X mouse model of infantile neuronal ceroid lipofuscinosis (INCL) for testing nonsense suppression therapy” outlines the model generated by Pearce and his team.

According to the National Organization for Rare Disorders, approximately 30 million people

in the United States suffer from a genetic disorder like Batten disease.

A change in the DNA sequence or genome, called nonsense or frameshift mutation, is responsible for around 30 percent of genetic disorders. This results in a premature termination condon (PTC), which blocks the ability of the gene to code and creates disease. Identifying a way to lift the block could lead to potential therapies.

Batten disease, or neuronal ceroid lipofuscinoses, is a group of neurodegenerative disorders in children characterized by progressive onset of seizures, blindness, motor and cognitive decline and premature death. It is known for its early age of onset and devastating progression.

Frameshift mutations in the CLN1 gene account for more than half of all Batten disease cases.

Using the novel Cln1R151X gene developed by Pearce, his lab was able to mirror the characteristics of human Batten disease in mice, including gene mutations and enzyme activity, and test methods to ignore the PTC. Eventually, those methods could be tested on children with Batten disease and translated to other genetic disorders.

Associate Scientist Kristi A. Egland, PhD, of the Cancer Biology Research Center, presented to a group of students at The Sanford PROMISE Discovery Days.

Discovery Days Continues to Attract Teens from Across the Region On November 20 The Sanford PROMISE hosted over 270 teens at Science Discovery Day. Discovery Days provide high school students with hands-on science opportunities at the Sanford Research labs. This year’s keynote speaker was Brock Rops, Area Health Education Center education coordinator.

Participating schools this year sanfordhealth.org | 9

“To better understand how to treat genetic disorders in humans, it is important we engineer an accurate animal model to conduct research,” said Pearce. “This model has the potential to lead to new therapeutic treatment strategies designed to correct the flaws in DNA that underlie thousands of diseases affecting millions of people worldwide.”

Pearce Study Honored

by National Journal A study by Sanford Research’s David Pearce, PhD, that reveals the role of a protein in nervous system function, was a Journal of Biological Chemistry “Paper of the Week.”

“The human synaptic vesicle protein, SV2A functions as a galactose transporter in Saccharomyces cerevisiae” was in the top 2 percent of manuscripts reviewed by the Journal of Biological Chemistry, according to its editorial board members and associate editors. The journal publishes more than 6,600 papers each year but selects a limited number as “Papers of the Week.”

A Pearce-led team explored how the protein SV2A behaves as the target for an antiepileptic drug called levetiracetam. SV2A is a membrane protein found on synapses in the neuronal and endocrine systems.

By expressing the protein in yeast strains, Pearce discovered SV2A aided in growth in yeast containing galactose, which is a type of sugar.

“The newly identified galactose transport capability of SV2A may have an important role in regulating/ modulating synaptic function,” said Pearce. “This will provide greater insight into understanding and potentially targeting treatments for seizures that occur in many conditions, including Batten disease.”

Media visited the Sanford Sports Complex to get footage of Sanford’s new sport testing system as part of a new partnership with Sport Testing, Inc. The equipment uses real-time technology to capture athletic-performance data that can be used for research.

Sanford Researchers Awarded NIH Grant to Explore American Indian Infant Mortality

Amy Elliott, PhD

Jyoti Angal

Sanford Research’s Amy Elliott, PhD, and Jyoti Angal have a secured more than $1.7 million in grant funding from the National Institutes of Health to study methods to reduce infant deaths in American Indian communities.

The project, “CBPR Initiative in Reducing Infant Mortality in American Indian Communities,” received a five-year award under

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the NIH’s Eunice Kennedy Shriver National Institute of Child Health & Human Development.

According to the South Dakota Department of Health, infant mortality rates among American Indians are nearly double that of white infants. In 2013, the infant mortality rates in South Dakota were 11.2 per 1,000 live births among American Indians and 5.3 per 1,000 among the white population. This difference is largely driven by postneonatal mortality, or infant deaths between 1 and 12 months of age.

Post-neonatal mortality rates are primarily related to sudden infant death syndrome (SIDS), unsafe sleep environments and other environmental and preventable conditions. South Dakota’s postneonatal mortality rate in American Indian communities was 367

percent higher than the white infant mortality rate in 2013.

Using community-based participatory research methods, Elliott and her team will work with the Oglala Sioux Tribe and partners in Rapid City to identify cultural factors that affect infant sleep practices and then develop strategies for intervention that are community endorsed and culturally driven.

“We are hoping to establish a costeffective model to decrease mortality that is also self-sustainable and can build upon current programs,” said Elliott. “Findings could also provide a model for intervention that could be applied to other highrisk communities to help prevent sudden infant death syndrome and other sleep-related deaths.”

Elliott is director of and a senior scientist at the Center for Health Outcomes and Prevention Research at Sanford Research.

Sanford, Sport Testing Partner to Improve Athletic Assessment A partnership between Sanford Health and Sport Testing, Inc., will bring the latest tools in athletic assessment and research to the region.

The two organizations have announced an agreement that makes Sanford the official sports medicine and research partner of Sport Testing, an athletic-assessment technology company based in Toronto, Canada. The relationship gives Sport Testing access to the expertise of Sanford’s robust roster of orthopedics and sports medicine providers and respected research arm.

The Sport Testing system, which includes both hardware and software, uses real-time technology to capture athletic-performance data and offers comprehensive solutions to store, analyze and disseminate that information.

Sport Testing utilizes wireless technology to identify athletes with Sport ID bands; results from assessments can be accessed by testers and athletes online and

displayed on an on-site Sport Board.

Sport Gates are used for timebased tests like a 40-yard dash, while other assessments integrate with smart phones and tablets.

“The capabilities of the Sport Testing system when it comes to assessment technologies are unparalleled in this industry,” said Scott Hettenbach, Sanford POWER manager in Sioux Falls. “With Sanford’s expertise in sports medicine and athletic performance research, this partnership will enhance the athlete, improve safety and provide visibility for regional athletes.”

Sanford POWER in both Sioux Falls and Fargo and the Sanford Sports Science Institute will deploy the capabilities of Sport Testing to evaluate athletes and gather valuable data for research. The system will also allow Sanford POWER to host pro-level combines--complete with live results on site and online-across a variety of sports.

Sanford and Sport Testing are also developing a shared web platform and mobile app that will be utilized

by Sport Testing users worldwide.

Furthermore, the partnership includes the integration of Sanford SCORE, an athletic-readiness assessment designed by the Sanford Sports Science Institute, into the Sport Testing system.

“This cutting-edge equipment provides us with accurate, reliable data that will enrich the sports science research already being performed at Sanford,” said Thayne Munce, PhD, associate director of the Sanford Sports Science Institute and the primary developer of Sanford SCORE. “Together, Sport Testing and Sanford SCORE are setting new standards in athletic assessment that will help athletes test, improve and compete at the highest level.”

Sanford POWER will join an international network of Sport Testing certified partners, and the Sanford Fieldhouse will be the official training center for all future testing partners in the United States.

Sanford Sports Science Institute Publishes Findings on Brain Injury Risk in Youth Football Thayne Munce, PhD

The force of head impacts in youth football can be similar to high school and college, but may not necessarily affect short-term neurological function in children, according to a study authored by Sanford Health’s Thayne Munce, PhD, and colleagues and published by Medicine & Science in Sports & Exercise.

Munce and the Sanford Sports Science Institute team in Sioux Falls monitored 22 local youth football players 11 to 13 years of age during a single season of 27 practices and nine games. Each player wore sensors in his helmet that measured head-impact frequency, magnitude, duration and location.

Players were additionally screened prior to and after the season for select clinical measures like balance, visual reading speed, reaction time and self-reported symptoms.

More than 6,000 head impacts were recorded and found to be similar in magnitude and location to those in high school and college football but less frequent.

The study, “Head impact exposure and neurologic function of youth football players,” found head impacts that players sustained throughout the season were not associated with changes in neurologic function.

“The body of knowledge related to concussion and brain health in youth football players is limited; this is the first time associations between head impacts and neurologic function has been studied in this age group,” said Munce. “Because this area of research is relatively new, contributing noteworthy data on this population is incredibly valuable to further our understanding of this important health issue and positively impact the safety of the game.”

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translational,” said David Pearce, PhD, president of Sanford Research.

“By teaming with NDSU, two like-minded organizations are coming together to better serve the health needs of this region.”

Profile launched in Sioux Falls, South Dakota, opening its first store front in November 2012. Today, it has 18 locations in six states, including two in Fargo-Moorhead, with more planned openings by the end of 2014.

NDSU and Sanford Health will conduct collaborative research on human nutrition, weight management and other dietary-related areas as part of a seed-grant initiative.

The research will address key objectives of the Profile by Sanford® program.

Munce is associate director of the Sanford Sports Science Institute, which conducts research, assesses athletes, provides current educational information and develops guidelines and policy for safe and appropriate exercise, training, and sports participation.

The group’s studies on concussions and brain health in youth football have also appeared in the Journal of Child Neurology and the Journal of Science and Medicine in Sport.

NDSU, Sanford Health Research Partnership Focuses on Human Health, Nutrition North Dakota State University and Sanford Health will conduct collaborative research on human nutrition, weight management and other dietary-related areas as part of a seed-grant initiative developed between the two organizations. The research will address key objectives of the Profile by Sanford® program.

Profile is a weight-management program that uses customized meal plans, health coaches and real-time technology. It was developed by Sanford physicians and researchers.

NDSU researchers will have opportunities to collaborate with investigators from Sanford Research on topics like metabolism, food choices and consumption, prenatal nutrition, genetics, development of sensors that monitor wellness factors and food manufacturing 12 | discoveries

and nutritional interactions with the human microbiome.

Research findings relevant to Profile will be considered as the program evolves and expands.

Sanford will provide $250,000 annually for five years for the seed-grant program.

“This collaboration with Sanford represents additional opportunities for faculty to conduct research with potential wide-ranging implications for positive impact on human health,” said NDSU President Dean L. Bresciani.

The Profile system utilizes mealreplacement products, nutritionally complete foods, qualified health coaches and client tracking of body weight, blood pressure and physical activity through smart wireless technology. Jawbone UP24 activity trackers are integrated with the Profile app to allow members to track their movement and sleep patterns.

A new fitness tracker will provide additional measurable data helpful to members to monitor progress.

“This collaboration offers an additional opportunity to further serve the citizens of the region, while potentially making strides that contribute to important research on health and well-being,” said Kelly A. Rusch, NDSU vice president for research and creative activity.

“Sanford Research is dedicated to finding ways to conduct meaningful and quality research that is also

“Profile by Sanford continues to evolve and improve due to evidencebased research,” said Rich Adcock, executive vice president for Sanford.

“This partnership is important to our health system because Sanford Health values research that can contribute to its overall mission of health and healing.”

Seed-grant proposals are due March 16, 2015, and recipients will be announced in June 2015.

More information is available on the NDSU Research and Creative Activity website.

SAB Biotherapeutics Helping Fight Hantavirus Scientists investigating the potentially deadly hantavirus are using specially bred cows developed

by SAB Biotherapeutics, Inc., to develop protective antibodies against the disease. Their work, published in an online edition of Science Translational Medicine, provides proof of concept for producing antibodies against a broad range of human pathogens.

SAB Biotherapeutics, Inc., is a close partner of Sanford Research and is located at the Sanford Research Center in Sioux Falls.

Hantaviruses cause a condition known as hantavirus pulmonary syndrome (HPS), which has a case fatality rate of 35 percent to 40 percent. Currently, there are no licensed vaccines, prophylactics or therapeutics to prevent or treat this highly pathogenic disease.

This research involved the use of specially bred “transchromosomal”

cows that have been engineered

by SAB Biotherapuetics, Inc., to produce fully human IgG antibodies.

Investigators first immunized the cows with DNA vaccines targeting two types of hantaviruses, Andes virus and Sin Nombre virus. The team collected plasma from the cows, purified the human IgG antibodies, and tested the material for its ability to neutralize the two different viruses.

The purified human antibodies had “potent neutralizing activity against both hantaviruses,” according to the paper’s first author, Jay W. Hooper, PhD, of the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID).

To assess the efficacy of the antibodies, Dr. Hooper’s team used a hamster model of Andes virus, the predominant cause of HPS in South America and the only hantavirus known to be transmitted person-toperson. Infection of Syrian hamsters with Andes virus, as demonstrated in earlier studies at USAMRIID, results in a disease that closely mimics human HPS in incubation time, symptoms of respiratory distress, and disease pathology.

This makes it an ideal system for evaluating the feasibility of postexposure protection strategies.

As described in the publication, seven of eight hamsters treated with the product survived with no signs of disease. In contrast, all eight hamsters treated with control human IgG purified from unvaccinated transchromosomal cows developed lethal HPS. Similar experiments were performed demonstrating that the purified human antibodies also protected immunosuppressed hamsters against lethal disease caused by Sin Nombre virus. This virus, which causes HPS in the US and Canada, has been associated with notable hantavirus outbreaks, including the cluster of cases at Yosemite National Park in 2012.

polyclonal antibody approach to treatment is feasible. However, the immune plasma is in short supply and must be matched to each patient’s blood type. The transchromosomal cows used by USAMRIID collaborator SAB Biotherapeutics, Inc. offer the opportunity to produce large quantities of antibodies that are fully “human,” meaning they will not be seen as foreign antigen by the human immune system.

According to Dr. Sullivan, this technology can be used to rapidly respond to many types of diseases, as the development time from first vaccination to high-titer, fully human polyclonal antibody is just a few months. He added that each animal can produce up to several hundred or even a thousand human doses of antibody per month, making the platform very scalable, based on data from this and other studies.

According to the authors, this is a significant advantage over other animal-derived polyclonal antibody approaches to the treatment of disease, where the antibody must be treated with enzymes to “despeciate” the antibodies to prevent a condition known as serum sickness. Moreover, it is possible that the human IgG will be capable of interacting with the human immune system to neutralize and clear virus in ways that despeciated antibodies cannot.

“Monoclonal antibodies targeting infectious agents are most effective when combined into cocktails,” said Dr. Hooper. “The transchromosomal cows allow us to rapidly produce large quantities of polyclonal antibodies that are, in effect, natural cocktails targeting specific threat agents like Andes virus and Sin Nombre virus.”

“This study represents the first time that DNA vaccines have been used to produce a hyperimmunized response in a human antibodyproducing large animal species,” said Eddie Sullivan, PhD, CEO of SAB Biotherapeutics, Inc. “Furthermore, the animal studies show that the human antibody is protective in the animal model presented.”

Now that proof of concept has been demonstrated, Dr. Hooper said, the next step is to secure funding and approval for Phase I clinical trials in humans to assess the safety profile of the antibodies.

Pearce Leads International Rare Disease Discussion in China Sanford Research President David Pearce, PhD, co-chaired a session

Sanford Research partner, SAB Biotherapeutics, is working to develop protective antibodies against the potentially deadly hantavirus.

Recently, according to Dr. Hooper, scientists in Chile have had some success in using convalescent plasma from HPS survivors to treat the disease, which suggests that a sanfordhealth.org | 13

for a subsidy in 2015, enrollees must meet the following criteria: •H ave a household income from one to four times the Federal Poverty Level (FPL). The subsidy range is from $11,670 for an individual and $23,850 for a family of four at 100 percent FPL, to $46,680 for an individual and $95,400 for a family of four at 400 percent FPL.

Sanford Health Plan has grown to over 100,000 members because of the commitment of the Health Plan’s 160 employees and over 1,000 agents who share the mission of being dedicated to the work of health and healing.

on Diagnostics of Rare Diseases at the 2nd International Rare Diseases Research Consortium (IRDiRC) Conference in Shenzhen, China November 7-9.

The IRDiRC teams up researchers and organizations investing in rare diseases research in order to achieve two main objectives by the year 2020, namely to deliver 200 new therapies for rare diseases and means to diagnose most rare diseases.

A number of grand challenges are being addressed through collaborative actions to reach these 2020 goals, such as establishing and providing access to harmonized data and samples; performing the molecular and clinical characterization of rare diseases; boosting translational, preclinical and clinical research; and streamlining ethical and regulatory procedures.

14th International Conference on Neuronal Ceroid Lipofuscinoses In October, faculty from the Sanford Children’s Health Research Center attended the 14th International Conference on Neuronal Ceroid Lipofuscinoses (NCL) in Cordoba, Argentina. The NCLs are a family of rare lysosomal storage disorders that affect 1:100,000 children worldwide. At Sanford Research, the laboratories of David Pearce, PhD, Jill Weimer, PhD, and Michael Kruer, MD all have research projects focused on understanding the underlying causes of NCLs as well

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as exploring therapeutic strategies for preventing or delaying the onset of these devastating diseases.

Faculty from the Pearce and Weimer labs were able to present the work that is being done here at Sanford Research to their peers worldwide.

eIRB System Now Live Sanford Research has launched a new eIRB (Internal Review Board) system for clinicians and scientists pursuing human subject research.

The new automated system, which went live January 23, offers streamlined capabilities and can be accessed from anywhere with internet access. The eIRB can be accessed through Sanford Connect in the Policies and Procedures section of Sanford Research. For more information, contact IRB Director Deb Langstraat, Sanford Human Research Protection Program, at debra.langstraat@ sanfordhealth.org or (605) 312-6434.

Sanford Health Plan Sanford Health Plan Participates in Federal Marketplace for Second Year Sanford Health Plan is once again participating in the federal Health Insurance Marketplace, HealthCare.gov, for South and North Dakota. The federal open enrollment period commenced November 15, 2014 and runs through February 15, 2015. In order to qualify

•N ot have access to affordable coverage through an employer (including a family member’s employer).

•N ot be eligible for coverage through Medicare, Medicaid, the Children’s Health Insurance Program (CHIP), or other forms of public assistance.

•H ave U.S. citizenship or proof of legal residency.

• I f married, must file taxes jointly in order to qualify.

As part of one of the largest integrated health systems in the nation, Sanford Health Plan members receive valueadded discounts on other Sanford services, including 50 percent off a Profile by Sanford membership, 50 percent off heart and lung screenings, 10 percent off of Sanford optical services, and 10 percent off of cosmetic dermatology and plastic surgery services not covered by a plan.

Through Sanford’s innovative electronic health record, all members can access increased value through My Sanford Chart e-visits, priced at $40, and video visits, priced at just $55; both covered by Sanford Health Plan with a co-pay.

Sanford Health Plan continues to offer affordable plans in Iowa, Minnesota, North Dakota and South Dakota, and is the sole Medicaid Expansion carrier in North Dakota.

Sanford Health Plan has grown to over 100,000 members because of the commitment of the Health Plan’s 160 employees and over 1,000 agents who share the mission of being dedicated to the work of health and healing.

Sanford International Clinics Sanford Health Opens Pediatric Clinic in Kunming, China

Jim Slack

Zhiguang Guo, PhD

Sanford Health opened a pediatric clinic in Kunming, China, as part of its International Clinics initiative in October. This quickly growing area of China has a significant need for health care, particularly with children.

For this clinic, Sanford collaborated with YMCI Calmette Medical Investment & Management Company, Ltd., a state-owned company of the Yunnan Provincial government.

YMCI Calmette currently operates the non-profit First Hospital of Kunming, which was established in 1914 and is rated as one of the top-100 hospitals in China. YMCI Calmette also developed a new 1,100-bed hospital complex in the northern part of Kunming that includes the new Sanford International Clinics location.

The new pediatric clinic includes 14 exams rooms, six treatment rooms, an education and training room and general office space. The goals of

the pediatric clinic include shifting the focus of care from acute illness to health and wellness, incorporating evidence-based practices and clinical practice guidelines into clinical care and creating workflows that increase efficiency, enhance patient safety and improve patient satisfaction, all while serving the pediatric health needs of a rapidly growing city.

“This area of Kunming is a perfect fit for our International Clinics initiative,” said Jim Slack, vice president of Sanford International Clinics. “This partnership with YMCI Calmette, its work to build a state-of-the-art hospital and the growing population of Kunming all fit together with what we hope to accomplish.”

With a population that surpasses 6 million, Kunming is the political, economic, communications and cultural hub of Yunnan and the seat of the provincial government.

The pediatric clinic is two stories and 18,000 square feet with the capacity to hold up to 10 primary care pediatric physicians. YMCI Calmette may also utilize the clinic for rotating pediatric sub-specialists.

general manager. “This partnership and new clinic will greatly benefit thousands of children and families.”

YMCI Calmette will own the pediatric clinic, and Sanford International Clinics will manage the day-to-day operation as well as provision of medical services.

The children’s clinic will also have connection to Sanford Health’s extensive clinical, research and administrative expertise in South Dakota.

The connection to Kunming and YMCI Calmette was made possible through Zhiguang Guo, PhD, a research scientist with Sanford who previously worked with YMCI Calmette physicians.

In addition to the planned clinic for Kunming, China, Sanford International Clinics has opened facilities domestically in Oklahoma, California and Oregon.

Internationally, Sanford has partnered with the government of Ghana, Africa, to build as many as 300 clinics in that nation.

Sanford also is pursuing projects in Mexico and evaluating several other locations worldwide.

After being open just two months, the clinic reported seeing over 20 patients a day. “We’re pleased to work with Sanford to provide care to children in this region of China,” said Li Li, MD, First Hospital of Kunming president and YMCI Calmette

Sanford International Clinics opened its Kunming, China, location in October, made possible through Sanford researcher Dr. Zhiguang Guo’s connection to the area. This quickly growing area of China has a significant need for pediatric health care.

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events

give.

February 26: The Sanford PROMISE Community Lecture Series 5:30 p.m.

February 27: 5th Annual Sanford Rare Disease Symposium March 5: The Sanford PROMISE Community Lecture Series 5:30 p.m.

March 5-6: STEMWise Forum

If you are interested in providing philanthropic support for any of the research or major initiatives featured in this publication, please contact the Sanford Health Foundation. Thank you.

March 20: STEM of Sports April 9: The Sanford PROMISE Community Lecture Series 5:30 p.m.

Sioux Falls Region: (605) 328-5700

April 10: Tourette Syndrome Symposium

Fargo Region: (701) 234-6246

June 13: It’s All About Science Festival

Bismarck Region: (701) 323-8450

June 18-19: 5th Annual Alex Rabinovitch Type 1 Diabetes Symposium – “Advances in Stem Cell Therapies for Type 1 Diabetes” * Unless otherwise noted, all events will be located at the Sanford Center, 2301 East 60th Street North, Sioux Falls, SD 57104

800-11000-0370 1/15

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Bemidji Region: (218) 333-5515 foundation.sanfordhealth.org Edith Sanford Breast Cancer Foundation: (855) 463-3484 edithsanford.org