The Sanford Project Issue 1

Issue 1

February, 2009

Finding a Cure for Type 1 Diabetes

We are pleased to present the first issue of The Sanford Project Newsletter outlining progress on Sanford Health’s attack on type 1 diabetes and news about broader scientific achievement in cell biology.

We hope our common-language approach to this technical subject, during what is an extremely exciting period, will be informative for people living with diabetes, their friends and families, scientists within the diabetes community, and others with an eye on The Sanford Project.

In our path toward a cure, we hope you become familiar with the tremendous development activities occurring at Sanford Health, an

The Sanford Project Seeks Cure for Type 1 Diabetes Focus on Beta Cell Regeneration and Autoimmunity On June 6, 2008, Sanford Health leaders announced the focus of The Sanford Project is curing type 1 diabetes via the body’s natural ability to regenerate beta cells. Identified as the attack on one of the greatest health concerns of our time, Sanford Health is dedicating health research resources to cure type 1 diabetes, also known as juvenile diabetes.

“The concept for The Sanford Project is to focus on a single,

pressing healthcare issue and establish a world-class research team to achieve significant progress within a reasonable time period,” said Sanford Health Executive Vice President Dave Link.

Regeneration research focuses on triggering the body to re-grow the insulin-producing beta cells that have been killed by the autoimmune response and to prevent destruction of the newly regenerated cells by

organization with humble roots planted firmly in South Dakota and the greater Midwest, and the industries of patient care, medical education and health research.

Also, visit www.sanfordproject.org to learn more and receive the most advanced information on our developments and discoveries.

Thank you for joining us on this exciting and historic journey.

David Link Executive Vice President, Sanford Health

the same autoimmune reaction.

“Beta cell regeneration is one of the fastest-growing and most intriguing areas of type 1 diabetes research,” stated Ben Perryman, PhD, Sanford Health Vice President of Research.

Sanford Health will assemble a team of top researchers to work on the project and plans an investment of $30 million over five to seven years.

Additional funding is expected from foundation and industry sources as well as the National Institutes of Health. The core of the research will be conducted in a developing 185-acre research park in Sioux Falls, South Dakota’s growing southwest corridor.

$5.00 or included within a $20 annual subscription to The Sanford Project via www.sanfordproject.org. All proceeds support type 1 diabetes research at Sanford Health.

Who is Sanford Health?

Sanford Health is a not-for-profit integrated healthcare system of 24 hospitals, 115 clinics and nearly 400 physicians in four states. The health system has garnered a decade-long commitment to health research through collaborative efforts with the University of South Dakota and the Sanford School of Medicine at USD. Beyond this partnership that supports health research including cardiovascular, signal transduction, cancer biology, health disparities and disabilities, nutrition and metabolic diseases, women’s health, pediatrics, and genomic research, the Sanford Children’s Health Research Foundation is a multisite partnership with The Burnham Institute for Medical Research.

This agreement of more than $20 million includes funding for up to six principle investigators and a variety of associate scientists and staff.

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What is The Sanford Project?

The Sanford Project is a key program effort with the goal of enabling Sanford Health to contribute to advancing biomedical research even as the full footprint of its research infrastructure is being developed. This effort, combined with the activities of Sanford Research/USD, will eventually lead to an annual research budget of more than $100 million per year and a staff of between 300 and 350 investigators, associate scientists and administrative staff.

The concept for The Sanford Project is to focus on a single pressing healthcare issue and establish a world-class research team targeted to making significant progress in addressing it within a reasonable time period. Sanford Health is planning an investment of $30 million per year to advance The Sanford Project; additional funding is expected from federal, foundation and industry sources.

What makes The Sanford Project different?

It is “designed for results” from its inception. Using a deliberative, objective-based identification and selection process, associates of Sanford Health and their representatives examined a wide range of pressing healthcare diseases and conditions to identify those in which innovative new treatment approaches were poised for development and could be carried out through a targeted research program housed at Sanford Health.

The Sanford Project is intended to be a new way of advancing biomedical research. Instead of creating barriers between the worlds of research and clinical treatment, The Sanford Project creates a bridge by focusing on opportunity-driven and resultsoriented innovation to address pressing, real-world healthcare needs.

Denny Sanford From Success to Significance On February 3, 2007, South Dakota businessman Denny Sanford set a new standard in healthcare philanthropy with an unprecedented gift of $400 million to Sanford Health.

The gift set the organization, the region’s leading healthcare system, on a path that would change patient care, education and research broadly.

Sanford is CEO of United National Corporation, First PREMIER Bank, and PREMIER Bankcard, headquartered

in Sioux Falls. In 2005, the 71-yearold businessman ranked 14th on the Chronicle of Philanthropy’s list of America’s Most-Generous Donors.

Mr. Sanford has given more than $70.5 million to U.S. charitable causes, including $20-million to Sanford Health for use in expansion projects involving the University of South Dakota’s School of Medicine.

In 2006, Mr. Sanford was named to Business Week’s list of 50 most generous philanthropists.

“Now is the time to set things in motion that can truly make a difference in people’s lives,” Sanford said. “My greatest desire is that this gift will create and sustain a momentum that results in major healthcare innovations and improvements in the human condition for generations to come.”

For more information on Mr. Sanford’s historic gift, please visit www.sanfordproject.org.

Todd & Linda Broin Chair of The Sanford Project Historic $10 Million Gift Creates Fund for Sanford Project Chair On July 10, 2008, Sanford Health received a $10 million gift from Todd and Linda Broin of Sioux Falls, SD to fund the Todd and Linda Broin Chair of The Sanford Project, the largest publicly-recorded gift given for the recruitment and support of a single research leader and that individual’s related research activities. ”The success of The Sanford Project is dependent on the expertise and dedication of a world-class research team,” said Sanford Health President

and Chief Executive Officer Kelby Krabbenhoft. “This generous donation from Todd and Linda Broin will allow us to support a lead researcher and the team who will attack and cure type 1 diabetes by focusing on beta cell regeneration.”

Linda Broin, who has lived with the disease for nearly 30 years, added, “We didn’t want it to be an endowment. We’re doing this for the cure. We want this to happen and believe it will happen here in Sioux Falls.”

“We came to the conclusion in our lifetime we want to give a gift that has meaning, and this is that one gift that has a lot of purpose,” stated Todd Broin.

To chair The Sanford Project, Sanford Health is currently recruiting a senior scientific leader with a superior record of accomplishment in type 1 diabetes research. sanfordproject.org • 3

Partnerships In its pursuit of a cure for type 1 diabetes, Sanford Health is partnering with the Juvenile Diabetes Research Foundation, the world’s leading charitable funder of diabetes research, and a leader in the newly emerging scientific field of regeneration — the innovative focus of Sanford’s groundbreaking diabetes project. This combination of a dynamic health care system with the major funder and pacesetter of diabetes research for more than three decades is unprecedented in diabetes science.

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A New Beginning Sanford announced in June that type 1 diabetes would be the principal focus of The Sanford Project. It was also announced at that time that Sanford would create a unique partnership with JDRF, which has funded more than $1.3 billion in diabetes research and has been a leader in setting the direction of science focusing on a cure for type 1 diabetes and its complications.

Sanford Health and JDRF will identify opportunities to speed the pace of regeneration research leading to a cure, working together in the recruitment of researchers and the review of regeneration-related science that will establish the scientific platform for the project.

Groundbreaking Science Regeneration involves triggering the body to re-grow or regenerate insulinproducing cells in the pancreas (which are destroyed by the autoimmune attack that causes type 1 diabetes). In the past few years, researchers have found evidence that insulin-producing beta cells can replicate or regenerate over time in healthy people, but not in those with type 1 diabetes. Tapping JDRF’s experience and expertise in regeneration, Sanford will build a world-class basic and clinical research infrastructure to investigate how beta cells regenerate, and develop novel therapeutics that utilize regenerative medicine to restore beta cell function and cure type 1 diabetes, without the need for transplants (which carry a range of complications and

Key Fact:

“ problems, particularly for children).

Sanford Health’s diabetes translational network provides a unique opportunity to incorporate the clinical components of patient-oriented care with scientific investigation into the most promising and fastest moving fields of diabetes research.

Decades of Progress Toward a Cure Type 1 (or juvenile) diabetes is an autoimmune disease that strikes children and adults suddenly, and requires multiple injections of insulin daily or a continuous infusion of insulin through a pump. Insulin, however, is not a cure for diabetes, nor does it prevent its eventual and

According to the National Institutes of Health, nearly 13 percent of adults age 20 and older have either type 1 or type 2 diabetes, but 40 percent of them have not been diagnosed.

devastating complications which may include kidney failure, blindness, heart disease, stroke, and amputation.

The mission of JDRF is to find a cure for diabetes and its complications through the support of research.

Since its founding in 1970 by parents of children with diabetes, JDRF has funded more than $1.2 billion in diabetes research, including more than $156 million in the last year. In that year, JDRF funded some 1,000 centers, grants and fellowships in 20 countries.

Regeneration is one of the five “cure therapeutic” areas in which JDRF research is focused. In addition to reversing the immune attack that causes type 1 diabetes, the restoration of insulin producing cells — either

”

by regenerating them or replacing them with working cells — is a key to a cure. The foundation’s innovative Regeneration Team was the first to incorporate multi-center, multidisciplinary team-science approaches to explore the early applicability and proof of concept of regeneration as a path towards a cure for diabetes.

JDRF’s portfolio of regeneration research has increased each of the last three years, and today includes the foundation’s first human clinical trials involving regenerative therapeutics.

JDRF is also a key advocate for NIH special funding for diabetes research, including regenerative science, and has successfully advocated for more than $1 billion in special diabetes funding over the past nine years.

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Contributors…

Pat Killian, PhD The Juvenile Diabetes Research Foundation

Dr. Kilian has extensive global management and scientific experience in both large pharmaceutical and biotechnology companies in the area of diabetes. From 1998 to 2001, she served as Vice President of Research for Pharmacia AB in Stockholm. Prior to joining Pharmacia, Dr. Kilian was Department Head, Cell Physiology, at Glaxo in Research Triangle Park, North Carolina. Dr. Kilian has also been involved in two start-up companies in California. She is co-founder and a board member of Kinexis, Inc., where she served as CEO from its inception to September 2005. Dr. Kilian also served as Vice-President, R&D, at gene/Networks, which was ultimately acquired by Parke Davis/Warner Lambert in 1998.

Science

Notes from The Sanford Project staff and collaborators…

JDRF’s Regeneration Research Goals Article by Pat Killian, PhD

Fred Levine, MD, PhD Sanford Children’s Health Research Center Burnham Institute for Medical Research Dr. Fred Levine is a Professor and Director of the Sanford Children’s Health Research Center at the Burnham Institute for Medical Research. Prior to that, he was a Professor in the Department of Pediatrics at the University of California, San Diego School of Medicine, where he continues to see children with inherited metabolic diseases. Dr. Levine received his undergraduate degree in biochemistry from Harvard and his MD and PhD in genetics from the University of Washington. His clinical training as a pediatric geneticist was at the Children’s Hospital of Philadelphia.

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The overall goal of JDRF’s Regeneration research is to cure type 1 diabetes by restoring the body’s ability to produce insulin. Our knowledge of beta cell biology and cell function is rapidly changing, and new advances are being made in regenerative medicine on an accelerated pace. For example: • While it was thought that all beta cells were destroyed by the autoimmune attack that causes type 1 diabetes, we now know from studies at UCLA that people with type 1 diabetics — even those who have had the disease for many years — are able to retain some residual beta cell mass. This finding suggests that using therapies to expand beta cells (while at the same time suppressing the immune response) may be therapeutically possible. JDRF-funded investigator at the University of Alberta, in Canada, have recently found that using two agents, gastrin and glucagon-like peptide 1, may expand beta cell mass and at the same time suppress the immune response in animal experiments. These findings may have implications for human

use. With JDRF support, a small company, Transition Therapeutics, is partnering with the large diabetes company Lilly to investigate the use of such combination therapies in clinical studies in people.

• It was also thought that mature beta cells were incapable of being stimulated to replicate but this “dogma” is being challenged.

We are now gaining insights into mechanisms by which the body accommodates increased metabolic demands during pregnancy, growth, obesity, and other conditions by creating new insulin-producing cells. By understanding these physiologic mechanisms, it is possible that scientists can develop pharmacologic means to promote beta cell expansion. JDRF-funded investigators at Stanford and at the University of Pennsylvania have identified genes that are crucial for insulin-producing cell expansion and replication during pregnancy.

And scientists at Burnham Institute, with JDRF funding, are performing chemical screens for new potential therapeutics to promote beta cell regeneration from mature beta cells.

• Finally, conventional scientific wisdom suggested that new beta cells could not be made from progenitor cells after birth.

But findings by JDRF funded investigators at Vrije University in Brussels showed there is indeed a progenitor cell in adults for beta cells, which could potentially be harnessed to provide a cure for type 1 diabetes. JDRF is currently looking to identify pancreatic progenitor cells in people.

With each of these and other new findings, the “book” of beta cell biology is being rewritten and entirely new chapters are being added.

To quote one JDRF researcher,

the dogmas surrounding beta cell regeneration are being rewritten — and the dogmas are becoming old “dogs.” JDRF’s support has been pivotal in bringing about this important paradigm change in our understanding of how insulin-producing cells develop and regenerate, allowing new strategies for the treatment of type 1 diabetes by targeting cell regeneration and replication.

JDRF’s Regeneration Program partners with top investigators at leading institutions, and with pharma and biotech companies, to fill critical gaps in our understanding of beta cell regeneration and to translate these findings to the clinical setting. Milestone-driven goals and objectives have been mapped and are revised on a continuing basis as our scientific knowledge grows, and

our field advances, are progressing and bottlenecks are avoided. We work closely with investigators to identify the most opportunistic research that accelerates the pace of science leading to a cure for type 1. More information about the Regeneration Program can be found on JDRF’s web site (www.jdrf.org).

While the hope of everyone connected to type 1 diabetes is that a “cure” is around the corner, and the importance of targeting beta cell regeneration as a therapeutic strategy is clear, we recognize there is still much more to do to advance this exciting but early research area. JDRF has partnered with Sanford Health and is committed to provide counsel, strategic direction and collaboration to ensure the investment in The Sanford Project is leveraged for success — and leads to a cure.

Beta Cell Regeneration JDRF’s Regeneration Therapeutic Program focuses on basic and clinical research aimed at developing therapies to restore and maintain insulinproducing beta cells to treat type 1 diabetes. This is one of the newest and fastest-growing areas of diabetes research, and JDRF has worked aggressively to build this promising field, funding $20.9 million last year alone. The two major approaches to regenerating beta cells are: increasing functional beta cell mass by promoting existing or residual beta cells to replicate, and producing new beta cells from progenitor cells residing in the pancreas. The Regeneration Program looks to translate research findings into therapies that regenerate beta cells, restore the body’s ability to produce insulin in response to blood glucose, and alleviate the need for insulin injections that people with type 1 diabetes need to take each day of their lives. sanfordproject.org • 7

Science

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How can we develop a new treatment for diabetes based on beta-cell regeneration?

Article by Fred Levine, MD, PhD

Beta-cells are the only cells in the body that make insulin, a hormone that regulates sugar metabolism in the body. These cells are absent or insufficient in both type I and type II diabetes. Thus, there is a great deal of interest in replacing or regenerating beta-cells as a way of treating and potentially curing diabetes. A major question in the field of beta-cell regeneration is how and even whether beta-cells turn over in human beings.

Under normal conditions, the total mass of beta-cells is about one

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gram. Given that an average person weighs about 70 kilograms, one can calculate that beta-cells make up about 0.001% of the body. Beta-cell mass generally remains constant in normal individuals. There is a gradual decline with aging but an increase during pregnancy. When individuals become obese, there is an early stage where there is a compensatory increase in beta-cell mass, but as time goes on and particularly when a person develops type II diabetes, beta-cell mass declines. Of course, in type I diabetes there is an almost

complete loss of beta-cells due to autoimmune destruction.

To begin to understand beta-cell regeneration, we should first consider the different types of cells in the pancreas, as these are the logical candidates for new beta-cells. A great deal of interest has centered on the beta-cells themselves. In that scenario, new beta-cells would arise from preexisting beta-cells by a process called replication, i.e., one cell dividing into two. While it is clear that betacell replication occurs during fetal

development and in young animals and humans, it is also clear that betacell replication declines rapidly with age, to the point where it becomes almost undetectable in adult humans.

Another possible source of new betacells is a stem cell. However, there has been tremendous controversy about whether such a cell even exists in the adult pancreas. We spent many years developing methods for asking whether stem cells that can become beta-cells are present in the adult human pancreas. In 2006 we published a paper in which the existence of such stem cells was demonstrated.

Adult stem cells have also been demonstrated in the mouse, using sophisticated genetically modified mice, a technology that obviously cannot be applied to human beings.

So what’s next? We are working to understand the process by which adult stem cells in the human pancreas become beta-cells. We believe that it will be important to understand at a molecular level what is happening so that we can manipulate the process and stimulate the formation of new beta-cells in individuals with diabetes.

One method that we are using involves screening many thousands of small chemicals for those that promote particular steps in the process of beta-cell formation. This is essentially the same technology that large pharmaceutical companies use to discover new drugs. As these experiments progress, we are looking forward to working collaboratively with our Sanford colleagues in Sioux Falls to test in animals molecules we discover, with the plan of eventually conducting clinical trials in patients with diabetes.

Key Fact:

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Researchers have learned a great deal about the underlying biology of autoimmune diabetes and can now predict who is at high, moderate and low risk for developing type 1 diabetes according to the National Institutes of Health.

”

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Research News Sanford Research/ USD Awarded $878,686 ADA Grant for Diabetes Research

More than 65 percent of people with diabetes die from heart disease or stroke, according to the American Diabetes Association (ADA). Sanford Research/USD announced today it has received an ADA Career Development Award to help understand why this occurs, which could ultimately save lives. The $878,686 grant over five years will be used to explore the connection between diabetes and susceptibility to heart disease in patients with both type 1 and type 2 diabetes. Qiangrong Liang, MD/ PhD and a team of researchers at Sanford Research/USD Cardiovascular Research Center will use the grant to expand the research capacity by recruiting staff and purchasing equipment and supplies.

“It is a great honor to be chosen as the recipient of this highly competitive grant,” Dr. Liang said.

The ADA Career Development Awards are designed to assist outstanding assistant professor level faculty 10 • The Sanford Project

investigators in conducting diabetesrelated research. Sanford Research/ USD is one of the very few institutions awarded this grant for 2009.

“It is a credit to Dr. Liang’s research team they were chosen for this very competitive award,” added Ben Perryman, PhD, Sanford Health Vice President of Research. “His team has already made significant discoveries, and this grant shows national recognition of the important work they are doing.”

SEARCH for Diabetes in Youth Study Nearly 154,000 children in the United States have some form of diabetes, according to results of the SEARCH for Diabetes in Youth study — a decade-long examination of the disease and its trends in youth. This $22 million, multi-center study, which began in 2000, uses surveillance databases maintained by networks of endocrinologists, hospitals, care providers, and health plans from six centers around the country.

Based on a one-time count in 2001, SEARCH estimates approximately 154,000 diabetes cases among youth 0 to 19 years old, with the vast majority of cases still being type 1 diabetes. The study has found that while type 2 diabetes is still rare among children younger than 10, the risk of developing the disease increases with age, especially among certain minority groups. The study is identifying risk factors for diabetes

complications, learning how youth diabetes progresses and how types 1 and 2 differ. Researchers will report on diabetes trends among U.S. Youth in 2010. NIDDK Diabetes Dateline, Spring/Summer 2008.

Building on Work of the Human Genome Project The Type 1 Diabetes Genetic Consortium, funded by the National Institute of Diabetes and Digestive and Kidney Diseases and its collaborators are organizing and implementing international efforts to identify genes and gene variations that determine an individual’s risk of developing type 1 diabetes or related autoimmune diseases. The consortium is building on the work of the Human Genome Project, which spelled out the contents of human genes, and the International HapMap Project, which is identifying the points at which gene sequences differ from person to person. These groups are identifying which of these genetic differences is significant for type 1 diabetes.

The first phase of the project involved recruiting families, particularly those with multiple siblings with type 1 diabetes, and the consortium created a database containing clinical, genetic, and medical history information to facilitate the search for susceptibility genes. In the future, the database and centralized DNA repository will serve as a resource for genetics research in a variety of areas. NIDDK Diabetes Dateline, Spring/Summer 2008.

Clinical Trials Frequently Asked Questions about Clinical Trials

Before new treatment or a new drug or is approved by the U.S. Food and Drug Administration (FDA), it must be shown to be both safe and effective.

This is accomplished by a clinical trail designed to test, evaluate and prove that new drugs and new treatment plans are safe and effective.

Clinical trials help researchers explore new treatments options and find better therapies.

Why do people volunteer for clinical trials?

People participate in clinical trials for a variety of reasons. Some people who are very sick or not responding to standard treatments join clinical trials in order to receive new, investigational treatments. They are hoping that this treatment — possibly a new drug or a new combination of drugs — will work better for them than standard therapy. This is not always the case as new treatment strategies may not work or may have side effects. For this reason, all people in clinical trials are carefully monitored. Frequent medical exams and tests are performed to assure their safety. Other people participate in clinical trials to contribute to medical science and to help doctors and researchers find better ways to help others.

Are there risks in clinical trials?

The process of evaluating new treatments can involve some risk. All drugs used in clinical trials have been extensively tested in laboratory experiments. However, some side effects do not become apparent until the treatments are given to humans. The progress of patients in clinical trials is constantly monitored.

Periodic reviews of test results and other statistics are carried out while the trial is underway. If, at any time, a new treatment is found to be harmful to the study participants, the trial will be terminated.

What are the different phases of clinical trials?

Clinical trials are traditionally divided into different phases. Each phase is designed to gather specific information about the drug or treatment being studied.

Phase I trials

These trials are the first human tests of new drugs or therapies. They typically involve small numbers of volunteers and are designed to determine the best dose of the drug and to check for any side effects. Because Phase I trials use treatments that have never been tested in humans, they may involve significant risks.

Phase II trials

If a treatment is shown to be safe and well tolerated, it moves on to Phase II trials. These trials involve many more volunteers and are designed to see how well the treatment works, usually in a small group of patients.

Phase III trials

If the treatment is effective in Phase II trials, it moves on to Phase III trials. Hundreds or even many thousands of patients may participate in these studies. They are aimed at further testing how well the treatment works. Often Phase III trials compare the new treatment to an already existing, standard treatment in a randomized fashion.

Phase IV trials

These trials are conducted after a drug has been approved by the FDA and are on the market. Phase IV trials typically involve a very large number of participants and are designed to evaluate new uses of existing therapies or to detect side effects that were not apparent during Phase III studies.

Who pays for the treatment in a clinical trial?

For the most part, the drugs used in clinical trials are given free of charge to the study participants. However, there may be other costs associated with the trial, such as blood work, x-ray tests, and travel expenses.

Most health insurance companies do not cover the costs associated with clinical trials. However, Medicare covers all routine patient care costs associated with clinical trials. You should contact your insurance company and the clinical trial investigator to understand any associated costs before enrolling in a trial. sanfordproject.org • 11

Clinical Trials

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Is a referral from my physician required for participation in a clinical trial?

No. In order to participate in a clinical trial you will be evaluated by the medical staff conducting the study to make sure you are eligible for the study. Once the details of the trial have been explained, it is up to you to decide if you wish to participate or not. You should discuss participation with your own physician, as well as family prior to enrolling in a clinical trial.

Can I still see my regular doctor if I am participating in a clinical trail?

Yes. Clinical trials do not replace your normal health care. In fact, the regular doctors of trial participants should be updated regularly by the trial coordinators.

References: American Diabetes Association www.diabetes.org Department of Health & Human Services, Food & Drug Administration www.fda.gov

Type 1 Diabetes Clinical Trials By participating in clinical trials you play an important role in the fight to treat and cure Type 1 Diabetes. For more information on these clinical trials visit www.clinicaltrials.gov.

Prospective Assessment in Newborns for Diabetes Autoimmunity (PANDA). Phase I Observational No safety issues. Male and female newborns, young children, and adults with or without type 1 diabetes.

This study is designed to identify people who are at risk for developing type 1 diabetes, based on their genetics, family history and autoimmunity status, and to understand the role genetics plays in the development of the complications associated with type 1 diabetes in patients already affected by type 1 diabetes. Blood samples are taken, preserved and studied. Contact Diane I Hopkins, MS, CCRC (706) 721-4161 dhopkins@mcg.edu or Leigh Steed, RN, CCRA (404) 252-0844 lsteed@mcg.edu Refer to ClinicalTrials.gov identifier: NCT00649246 12 • The Sanford Project

PROCHYMAL™ (Human Adult Stem Cells) for the Treatment of Recently Diagnosed Type 1 Diabetes. Phase II Interventional with drug PROCHYMAL™ Male and female adults ages 18-30 diagnosed with Type 1 diabetes in the past 16 weeks. Other health criteria apply such as weight and blood pressure.

This study is designed to establish the safety and efficacy of multiple administrations of PROCHYMAL™ in adults recently diagnosed with type 1 diabetes.

Insulin is the primary method of controlling diabetes by regulating blood glucose levels, but it may not reverse or prevent disease progression. The characteristics and biologic activity of PROCHYMAL™, suggest that it may be a good candidate for addressing this unmet medical need. Contact Dayna Buskirk (352) 335-9383 osiris@osiris.com Refer to ClinicalTrials.gov identifier: NCT00690066

Oral Insulin for Prevention of Diabetes in Relatives at Risk for Type 1 Diabetes Mellitus. Phase III Interventional with drug Oral Insulin No safety issues. Male and females ages 3-45 diagnosed with Type 1 diabetes before age 40 and started on insulin therapy within one year of diagnosis. Other health criteria apply. This study explores the potential role of oral insulin to delay or prevent Type 1 diabetes in relatives at risk for developing Type 1 Diabetes. Eligible participants will be randomized to receive either oral insulin or placebo daily. All participants will be seen at a study site for regular follow-up evaluations and contacted by phone in between visits to assess changes in diabetes status, medication compliance and adverse events. Participants will be followed until development of type 1 diabetes or the conclusion of the study (expected to last approximately 7-8 years). There are multiple study locations.

Visit www.clinicaltrials.gov and refer to ClinicalTrials. gov identifier NCT00419562 for contact information.

Clinical Updates Sanford Health Diabetes Center The Pediatric Diabetes Center at Sanford Children’s Specialty Clinic and Sanford Clinic Diabetes & Thyroid utilize a multi-disciplinary team approach to providing diabetes care and education to children and their families This team includes pediatric endocrinologists, endocrinologists, endocrinology nurses, certified diabetes educators, registered dieticians and social workers. While focusing on the immediate and long-term issues related to diabetes,

the team of medical professionals provides an opportunity for patients and their families to obtain support and guidance for all aspects of diabetes care and management.

A difficult disease to manage at home, patients that are diagnosed with diabetes begin with a series of education-related meetings with a skilled team of diabetes educators.

This staff helps patients and their families with individualized education tailored to their needs, including insulin administration and adjustment, nutrition, blood glucose monitoring and home care management. Patients also learn about insulin pump therapy and intensive insulin management.

Once patients have been educated on the daily practices required to treat the disease, they see endocrinologists each three to six months. Through the evaluation of growth disorders, a variety of treatments are offered including growth hormone therapy.

The endocrinology team also evaluates thyroid issues, adrenal conditions, early and delayed puberty, polycystra spectrum disorders and other endocrine conditions. While focusing on the immediate and long-term issues related to diabetes, our team of medical professionals provides an opportunity for patients and their families to obtain support and guidance for all aspects of diabetes care and management.

The endocrinology team participates in a variety of research studies and clinical trials to further growth hormone therapies and the treatment of diabetes. The physicians also travel to clinics throughout the region to provide care to patients close to home, reducing travel time and expense.

This team is also tied to the most comprehensive collection of pediatric and adult subspecialty services in the region. As patients with diabetes need other clinical care, physicians at the Sanford Diabetes Center have access to physicians in: cardiology, gastroenterology, nephrology, neurology and ophthalmology.

Adult patients with type 1 diabetes are seen by endocrinologists, family practitioners and internal medicine physicians. Sanford also has a gestational diabetes specialist at Sanford Clinic Women’s Health. sanfordproject.org • 13

Other Resources As research initiatives continue to develop, patients will have greater access to the most advanced therapies and technologies via clinical trials conducted concurrently by their physicians. Also, the planned Pediatric Residency at the Sanford School of Medicine of The University of South Dakota will provide a pipeline of talent to continue services to the region’s children. Type 1 diabetes programs may also be enhanced through Sanford Health’s relationship with the Mayo Clinic as well as the advancing data network provided by the health system’s integrated electronic medical record system, docZ. This system will help patients and physicians better manage treatment protocols and follow-up appointments.

U.S.News & World Report has recognized Sanford as a leader in Diabetes Care Sanford USD Medical Center has been recognized by the American Diabetes Association for Quality Self-Management Education. The Sanford Diabetes Program has 15 American Diabetes Association recognized sites throughout the health system. Certified Diabetes Nurses and Dietitians provide Self Management training for people of all ages.

With The Sanford Project investment and initiatives, Sanford Health will seek to end the challenges type 1 diabetes brings to children and adults alike. But, while the cure is sought, the team at the Sanford Diabetes Center will continue to strive to provide better and less-intrusive treatments, not just for survival, but for a greater quality of life.

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Sanford Contributes to Record-Setting JDRF Walk On January 31, more than 450 Sanford employees, families, and friends gathered to walk in the 2009 JDRF Sioux Falls Walk to Cure Diabetes. An overwhelming sea of blue Sanford t-shirts filled The Empire Mall, with Sanford walkers raising $21,056!

Support from Sanford walkers helped the local JDRF chapter raise $161,479 at this year’s walk. That well surpassed JDRF’s 2009 goal of $100,000!

Funds from the event will be used to support research and research related education for type 1 diabetes.

As part of Sanford’s dedication to finding a cure for type 1 diabetes, Sanford Health served as the presenting sponsor of this year’s JDRF Sioux Falls Walk to Cure Diabetes. The goal of The Sanford Project at Sanford Health is to research and cure juvenile diabetes. The mission of the Juvenile Diabetes Research Foundation International (JDRF) is to find a cure for diabetes and its complications through the support of research.

Sanford Health and JDRF International are working collaboratively to find a cure for type 1 diabetes, also known as juvenile diabetes.

This chronic disease strikes children suddenly, making them dependent on injected or pumped insulin for

the rest of their lives. Affecting approximately 3 million Americans, type 1 diabetes carries the constant threat of major health complications.

Taking insulin does not cure diabetes nor prevent the possibility of its eventual and devastating effects: kidney failure, blindness, nerve damage, amputation, heart attack, stroke, and pregnancy complications.

To learn more about The Sanford Project, partnership updates, clinical trial information and research findings, visit www.sanfordproject.org.

Key Fact:

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The long-term survival of those with type 1 diabetes has dramatically improved within the last 30 years according to the National Institutes of Health.

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JDRF’s CGM Research Named One of Top 10 Medical Breakthroughs of 2008 ABC News Lists Human Clinical Trial of Continuous Glucose Monitors Among Years Most Important Advancements The groundbreaking human clinical trial funded by Juvenile Diabetes Research Foundation that showed that continuous glucose monitors can improve diabetes control was cited by the ABC television network as one of the top 10 medical breakthroughs of 2008.

ABCNews.com polled top medical centers and physicians in putting together its list of the past year’s most important scientific advances.

The 10 developments chosen, which ranged from JDRF’s CGM trials to advances in Alzheimer’s research and an early blood test for Down syndrome, were considered the most important scientific breakthroughs by medical practitioners and the most interesting by readers.

The JDRF CGM trial was the first major, multi-center trial to document the benefits of CGM devices in helping people with type 1 diabetes better control blood sugar levels and reduce the risk of devastating complications.

CGM devices, manufactured by several companies and approved by the FDA as an adjunctive therapeutic for diabetes, are a small monitor connected to a sensor that people with diabetes wear, that provide both a real-time snapshot of the glucose levels of a person with diabetes, as well as trend information on whether glucose is moving upwards or downwards, and how fast. The devices also provide warnings when the glucose is becoming too high or too low — both dangerous conditions.

“The recognition the CGM trial is receiving will come as no surprise to people involved with diabetes

research,” said Dr. Alan Lewis, President and Chief Executive Officer of the JDRF. “These study results promise to be a cornerstone of our research into metabolic control and the development of an artificial pancreas, as it shows that these technologies can provide significant improvements in the lives of people with diabetes.”

Type 1 diabetes is an autoimmune disease in which the immune system attacks and kills off the insulinproducing cells in the pancreas.

Without insulin, sugar from food cannot be turned into energy, accumulates in the blood stream, and can cause death. After diagnosis, people with type 1 diabetes need to check blood sugar levels multiple times every day and give themselves multiple injections of insulin, or use a pump to infuse insulin - each day, every day, for the rest of their lives. While insulin can help control diabetes, it does not represent a cure; and even with insulin treatment, people with diabetes have significantly increased risks for devastating complications, including kidney disease, blindness, nerve disease, and heart disease. However, research has demonstrated that improved control reduces the risk of complications.

care-based practices at the Atlanta Diabetes Associates, the Joslin Diabetes Center, Kaiser Permanente Southern California, Nemours Children’s Clinic, Jacksonville, FL, the Lucile Packard Children’s Hospital at Stanford University, the Barbara Davis Center for Childhood Diabetes at the University of Colorado Denver, the University of Iowa, the University of Washington, and Yale University, and coordinated by the Jaeb Center for Health Research in Tampa, FL. “The CGM clinical trial results are very important, because they show that continuous glucose monitors are tools that can substantially improve diabetes control when used regularly. And better control can lead to a lowered risk of complications, fewer hospital visits, and importantly improved quality of life” said Dr. Aaron Kowalski, Program Director for Metabolic Control at JDRF.

As many as 3 million people in the U.S. have type 1 diabetes, with children representing half of those diagnosed each year.

The JDRF study was a randomized, controlled trial involving 322 patients spanning the age range of 8 to 72 years at 10 sites, which included academic, community, and managed sanfordproject.org • 15

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