iTolerance Inc., a San Mateo, California-based biotech company, has signed an exclusive license and intends to develop the therapy toward clinical use. The technology was co-invented at UofL and at the Georgia Institute of Technology with support from the National Institutes of Health and , which funds Type 1 diabetes (T1D) research.

“Our goal is to help people with Type 1 diabetes, so they don’t have to suffer the side effects that come with immunosuppressants,” said Haval Shirwan, inventor and gratis professor in the UofL Department of Microbiology and Immunology.

In Type 1 diabetes, a condition affecting some 1.6 million Americans, the body’s immune system attacks cells in the pancreas that produce insulin, a hormone that regulates blood sugar. As a result, patients that receive pancreatic islet transplants need to be placed on immunosuppressants and cope with the possible side effects, including loss of appetite, nausea and increased risk of infection.

The technology works by training the immune system to accept insulin-producing cells through transplanted islets — cells taken from the pancreas. The islets are laced with a recombinant protein pioneered by Shirwan and Esma S. Yolcu, a gratis faculty member at UofL, known as Fas ligand (FasL), which “teaches” the immune system to see new graft as beneficial rather than a threat.

Once the immune system has been re-trained, the idea is to transplant healthy islet cells so the patient again can produce insulin on their own.

The UofL scientists teamed up with researchers at Georgia Tech to generate a to the graft site to ward off rejection. The technology has the potential to be an “off-the-shelf” treatment, and the hydrogels which hold the islets can be prepared up to two weeks ahead of the transplant. The islets also don’t need to be modified for the individual patient.

“We look forward to leveraging the technology to locally and durably induce immune tolerance of organ transplants,” said Cameron Gray, founder and chairman of iTolerance. “We believe the technology has potentially far-ranging implications for engraftment.”

iTolerance holds an exclusive license to the technology through Georgia Tech and the��, which works with startups and industry to commercialize university-born technologies.

The center is located in the UofL Physicians Outpatient Center, 401 E. Chestnut St., and serves as the clinical arm of the UofL Diabetes and Obesity Center headed by Aruni Bhatnagar, PhD, which focuses on research into prevention of diabetes.

“It is immensely gratifying to see the science of diabetes prevention being implemented to improve the public’s health,” Bhatnagar said. “It is through programs such as this that we will turn the tide in the fight against the epidemic of type 2 diabetes.”

In addition to the CDC recognition, the UofL Physicians Diabetes and Obesity Center, in a partnership with ULP Department of Medicine, is recognized by the American Diabetes Association for Quality Diabetes Self-Management ����ֱ�� and Support.

The ULP Diabetes and Obesity Center was created in part from support by KentuckyOne Health to provide preventive care and education and to promote research in diabetes and obesity. The Center is directed by Sri Prakash Mokshagundam, MD.

“Once you have diabetes, you can’t get rid of it, but if you have prediabetes, which is higher than normal blood sugar levels, or if you are at risk for developing diabetes, you can prevent it with lifestyle changes,” Mokshagundam said. “Diabetes also can be effectively managed with physician-directed care.

“We want people to know they have the power to change their outcome.”

The program is directed by Registered Dietitian and Certified Diabetes Educator Beth Ackerman, who cited UofL’s own employee wellness program, Get Healthy Now, in earning the recognition.

“This recognition was made possible through collaboration with UofL Get Healthy Now and its director, Patricia Benson, assistant vice president for health, wellness and disease management,” Ackerman said. “We currently offer the program to UofL employees who are covered by the university’s health plan, and will begin offering it to other patients in January.”

The UofL Physicians Diabetes and Obesity Center works to:

• Elevate the health status of our community by raising awareness of the risks for diabetes and heart disease;
• Facilitate prevention and management programs;
• Be a resource to our patients and community health care providers; and��
• Support researchers in their efforts to fight the growing epidemic of diabetes and obesity.

The Diabetes and Obesity Center at UofL Physicians offers diabetes self-management education and support if a patient is newly diagnosed or has had diabetes for many years. The center’s diabetes educators assess each patient’s needs and help them individually or to enroll in an education class to meet those needs. Classes cover:

• Diabetes Prevention
• Diabetes Self-Management��
• Pregnancy Planning
• Diabetes Medications
• Diabetes and Technology
• Medical Nutrition Therapy
• Weight Management
• Monitored Activity Options

More than 84 million Americans – one in three adults��– now have prediabetes. Of those 84 million, nine out of 10 of them don’t know they have it. Without intervention, many people with prediabetes could develop type 2 diabetes within five years.

In Kentucky, diabetes and prediabetes are at epidemic levels, according to the American Diabetes Association. More than 531,000 people in Kentucky, or 14.5 percent of the adult population, have diabetes. Of these, an estimated 108,000 have diabetes but don’t know it, greatly increasing their health risk. In addition, 1.168 million people in Kentucky – 35.5 percent of the adult population – have prediabetes with blood glucose levels higher than normal but not yet high enough to be diagnosed as diabetes. Every year an estimated 27,000 people in Kentucky are diagnosed with diabetes.

“More than 90 million adults in the United States are obese and more than 30 million adults suffer from diabetes. Our faculty, staff and students work every day to understand the causes and impacts of both so that we can develop the next generation of preventions, cures and treatments,” said UofL President Neeli Bendapudi, PhD. “This group of dynamic researchers now is looking at how our environment, in the broadest sense of the word, plays a role. This understanding has the potential to change not just people in Louisville, but literally the world. This is some of what makes UofL a great place to learn, work and invest.”

Aruni Bhatnagar, PhD, director of the UofL Diabetes and Obesity Center and the recently created Envirome Institute, which houses the Diabetes and Obesity Center, earned a competitive renewal grant that provides funding for essential core programs for all researchers in the center. Additionally, the center grant helps set the director of the research with an emphasis on metabolic and inflammatory mechanisms leading to diabetes, obesity and insulin resistance; stem cell biology; and environmental determinants of cardiometabolic disease. This marks the second successful five-year renewal that Bhatnagar has earned.

Petra Haberzettl, PhD, assistant professor of medicine, and Bradford Hill, PhD, associate professor of medicine, received funding to examine the effects of air pollution on stem cell health.

Jason Hellman, PhD, assistant professor of medicine, received funding to explore how exercise can reduce inflammation. His previous work has shown previously uncovered new mechanisms of sustained inflammation in atherosclerotic lesions in diet-induced obesity.

Matt Nystoriak, PhD, assistant professor of medicine, received support to study how the molecule carnosine can be activated in protecting humans against airborne particulate matter.

Timothy O’Toole, PhD, assistant professor of medicine, earned a competitive renewal grant to gain a better understanding of how diabetic conditions and pollutant exposure affects small pieces of genetic materials that line blood vessels.

Joule’s son lives with type 1 diabetes.

To honor her late father and help improve the lives of those with type 1 diabetes, Joule has given $500,000 to the University of Louisville Foundation to establish the William Marvin Petty, MD, Research Fund. The fund is designated to support type 1 diabetes research at the UofL School of Medicine.

“I saw the toll diabetes took on my dad, and now my son is faced with the same disease,” Joule said. “I was��not happy that medical research has not come up with anything new in the 40 years my son has been suffering. I am putting my assets behind the UofL research team.”��

That research team includes Haval Shirwan, PhD, and Esma Yolcu, PhD, of the UofL Department of Microbiology and Immunology, who are working to develop techniques to prevent and treat type 1 diabetes with particular focus on transplantation of islet cells.

Type 1 diabetes is a chronic autoimmune disease in which the pancreas does not produce enough insulin, a hormone required to convert glucose to energy in the body. There is no cure for type 1 diabetes, and standard treatment involves regular injections of insulin, which is far from keeping blood sugar in balance.

Insulin is produced in the pancreas by a type of cells called islet cells. Individuals with type 1 diabetes have too few or altogether lack the type of islet cells that produce insulin to keep glucose at the proper level. In recent years, physicians have developed a treatment in which they transplant the needed islet cells into a patient. However, the patient’s immune system often rejects the transplanted islet cells over time, attacking and killing them. To keep the transplanted cells alive, patients must take immunosuppression medications, which have a number of undesirable side effects.

At UofL, Shirwan and Yolcu have pioneered a process to create a manufactured protein known as Fas ligand (FasL), to protect the islet cells from destruction by the patient’s immune system. This process, patented by the UofL Office of Technology Transfer, is called ProtEx^��technology. ProtEx is used to create FasL, which is then applied to islet cells to protect them from destruction by the immune system once they are transplanted into the patient.

Preclinical research has shown that FasL is highly effective in protecting islet cells in small animal models. However, additional testing is necessary before the therapy can be used in humans.

“Ms. Joule’s contribution will enable us to achieve an important milestone for further development of the technology towards clinical translation by performing efficacy and safety studies. We are very grateful for that support,” Shirwan said.

Greg Postel, MD, executive vice president for health affairs at UofL, said the university is grateful for the contribution to research by and in honor of members of the Louisville community.

“We are extremely pleased that Ms. Joule has elected to support this very promising research at the University of Louisville,” Postel said “We believe her donation will allow this research to improve the lives of type 1 diabetic patients sooner rather than later.”

With increasing evidence that an artificial pancreas can improve glucose control in patients with type 1 diabetes, investigators had sought to see if it could also help patients with type 2 diabetes.

The study also found the improved glucose control in patients with type 2 diabetes was achieved without increasing the risk of hypoglycemia. One of the major limiting factors in achieving improved glucose control is the increase in hypoglycemic events.

Conducted by researchers at the University of Cambridge and Manchester University in the United Kingdom, along with the University of Bern in Switzerland, the study was published to coincide with a presentation at the American Diabetes Association’s 78th Scientific Sessions in Orlando, Florida.��

It was notable as most studies of automated closed-loop insulin delivery systems include patients with type 1 diabetes, said Sri Prakash Mokshagundam, MD, an endocrinologist and diabetes specialist with University of Louisville Physicians. It also focused on hospitalized patients, where most studies have focused on outpatients who were already on insulin, he said. About 25 percent of hospitalized individuals have diabetes.

In the study, patients who were not already on a pump or sensor to control their diabetes prior to admission were placed on the system upon admission to the hospital. Mokshagundam said that using the technology in an inpatient setting has certain advantages, such as less burden on nursing staff as they try to manually adjust insulin doses. Meal-time insulin delivery still has to be planned by the health care team.

He said that while the technology helps in the acute setting, procedures need to be developed to transition it from acute to chronic care after patients leave the hospital.

He noted there also are some hurdles at this time to implementing the technology in the United States, as the technology used in the study has not yet been approved by the U.S. Food and Drug Administration for inpatient use here. A slightly different type of system has been approved for outpatient use, which uses a different algorithm to calculate the dose.

“The study that shows that this can be done, but we are still a ways off before this becomes routine practice,” Mokshagundam said. “There is some refinement needed.”

“Hopefully they’ll catch it, but what if they miss?” said Dr. Harpal Sandhu, an assistant professor of ophthalmology at the University of Louisville.

That was the inspiration behind new research done by Sandhu and colleagues at UofL, which aims to make the process of identifying diabetic retinopathy more objective by teaching software to diagnose. The results were published in the British Journal of Ophthalmology and the .

The team used a technique called machine learning to teach the software how to identify the condition, which occurs when high blood sugar levels cause damage to the blood vessels in the eye.

They showed the software pictures of eyes — tons of them, both healthy and unhealthy — until it “learned” what to look for when making a diagnosis. It learned to look for swollen vessels or leaking of blood into the eye, which could cause impaired or even lost vision.

When tested on more than 100 cases, the software got 94.3 percent of the diagnoses correct.

Sandhu said diagnosis of diabetic retinopathy is especially important, given the “epidemic proportions” of diabetes. According to the , the number of people with diabetes rose from 108 million in 1980, to 422 million in 2014.

The software combines two systems developed by the UofL team for optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). Together, they allow the machine to, non-invasively, get a clear view of the blood vessels in the eye and make a diagnosis.

The software works with a machine used by many optometrists and ophthalmologists to examine patients’ eyes. The automated technology could supplement care in areas where medical staffing is low and optical specialists are sometimes unavailable.

“We think this machine could be set up in the family doctor’s clinic,” said Dr. Ayman El-Baz, professor and chair of bioengineering, who was part of the development team.

He said the technology is part of a “new trend for using artificial intelligence in medicine.” Similar research is being done at UofL for diagnosis of other medical conditions, such as lung cancer and organ rejection.

The development was backed by from the Wallace H. Coulter Translational Partnership, which promotes collaborative translational research, and is currently available for through the UofL Office of Technology Transfer.

This project is “a great example of collaboration between engineers and clinicians to address unmet clinical needs,” said Jessica Sharon, director of the Coulter Translational Partnership at UofL, adding the resulting technology “has the potential to make a significant impact through commercialization to diagnose disease and improve patient outcomes.”

Open-angle glaucoma��is��a chronic and��multi-faceted disease that causes��optic nerve damage and visual field loss, and if left untreated��can eventually lead to blindness. One of the most important risk factors for the development of open-angle glaucoma is high eye pressure.��It��is��the second leading cause of blindness worldwide, and is expected to affect about 3 million Americans by the year��2020.��

Working with colleagues at Indiana University School of Medicine Department of Ophthalmology and in Italy, Gross found that diabetic open-angle glaucoma��patients who had reduced retinal blood flow experienced faster glaucomatous optic nerve��and��visual field��deterioration than��glaucoma��patients without��diabetes.

Some services require that participants meet certain criteria; staff in the booth can provide information.

Daily services

University of Louisville health care providers will be on-site in the Health Horizons Pavilion at the Kentucky State Fair, and three programs will be offering services each day:

• Mammogram screenings: Providers affiliated with the UofL James Graham Brown Cancer Center and Kentucky Cancer Program will provide mammograms. All screenings will take place in the privacy of the Horses and Hope Cancer Screening Van. Mammogram screenings will be billed to insurance, so participants should have their health insurance verification and photo identification handy. Yearly mammograms are covered by Medicare and most private insurance providers for women over 40. Special discounted rates are available to those without insurance.
• Vascular screenings, including carotid artery screen and ankle brachial index, will be provided daily at the fair, Aug. 17-27. A carotid artery screen is ideal for anyone with dizziness, ringing in the ears or anyone with a family history of carotid artery disease. It also is indicated for smokers and people with high blood pressure, high cholesterol or diabetes or for anyone who is over the age of 50. The test is administered by a registered technologist and uses ultrasound technology.��
• ����ֱ��, prevention and survivorship information from the Kentucky Cancer Program: The Kentucky Cancer Program is a statewide cancer prevention and control program, bringing together local organizations, providers and other partners in planning, implementing and evaluating cancer prevention and control efforts. The KCP staff and volunteers will be on-site providing information and giveaways to fair-goers with the goal of reducing cancer incidence and cancer death in Kentucky.

Women’s health

Staff from UofL Hospital’s��Center for Women & Infants��and��UofL Physicians-Ob/Gyn & Women’s Health��will be on hand at the fair to help women of all ages. The Center for Women & Infants specializes in both high-risk obstetrics and general maternity services and gives expectant families their choice of care from board-certified obstetricians and certified nurse midwives who practice with UofL Physicians-Ob/Gyn & Women’s Health.

At the fair, staff will be on hand to discuss urogynecology with providers from the Female Pelvic Medicine & Reconstructive Surgery practices, fertility specialists in reproductive endocrinology and infertility, the certified nurse midwifery program, family planning services, and our newest offering – Centering Prenatal Care.��

Emergency care, training

The UofL Hospital Level I Trauma Center and the Burn Unit will also both provide a variety of services at the fair.

The��Trauma Center��is the region’s only Level I trauma unit. Staff will train fair-goers to “Stop the Bleed” on Aug. 18. This innovative program uses a lifelike replica of the human thigh – complete with faux blood – to train participants in handling bleeds from wounds at the scene where they occur. On Aug. 22, the Trauma Center will participate in Senior Day at the Fair, and feature a walk-through demonstration to help older adults identify potential hazards, help prevent falls and improve balance. The Trauma Center staff will return on Aug. 26, with more trauma prevention activities.

The UofL��Burn Unit��is the region’s only dedicated adult burn unit and will provide safety information and activities for the entire family. Burn Unit personnel will be at the fair on Aug. 23.

Senior Day

Senior Day at the Fair will feature two programs that will only be available to fair-goers on that date, Tuesday, Aug. 22:

• UofL Hospital Pharmacists��will share information of interest to older adults, including diabetes, vaccinations, pharmacy services at UofL facilities and more. They also will be available to answer questions one-on-one with fair-goers about their medications and treatments.
• UofL Hospital Volunteers��will be at the fair to provide information on how fair-goers can serve others as a hospital volunteer. A wide array of service opportunities are available each year, from greeting guests to clerical service and more.

Also on Senior Day, the UofL booth will provide mammogram screenings, vascular screenings, colon cancer screenings, blood pressure checks, stroke assessments, women’s health information and a walk-through demonstration for older adults to help them avoid falls.

Specialty screenings

Several specialty services will be provided by UofL staff at the fair:

• UofL Physicians-Pediatrics��will be at the fair Aug. 19, offering vision and blood pressure screenings and a child safety demonstration.��
• UofL Physicians-Diabetes & Obesity Center��will be at the fair Aug. 23, providing screenings for prediabetes and diabetes. The screening requires a finger stick and the participant does not have to be fasting.
• UofL Hospital Infection Control��will be at the fair Aug. 24, with information on the importance of hand hygiene in preventing the spread of disease. The staff also will show fair-goers the benefits of getting annual flu vaccinations and provide information on when antibiotics should be used and when they should not.
• Carbon monoxide screening��will be available during the final four days of the fair, Aug. 24 through Aug 27. The carbon monoxide breath test shows the amount of carbon monoxide in the lungs and blood in an indirect, non-invasive manner. Breath carbon monoxide also is an indicator of the levels of approximately 7,000 toxic substances present in cigarette smoke, 69 of which are known to cause cancer. Participants will blow into a small handheld device for several seconds.

Cancer screenings and more��

Staff with UofL’s James Graham Brown Cancer Center, the Kentucky Cancer Program and the UofL School of Dentistry will be on hand to provide information, screenings and more. In addition to the aforementioned mammogram and vascular screenings:

• Head and neck cancer screenings: Provided Aug. 19 and 20, Aug. 22, Aug. 26 and Aug. 27, the UofL School of Dentistry and the Kentucky Cancer Program will observe the 25^th��anniversary of their collaboration in providing head and neck assessments at the fair. Dental students and faculty have conducted more than 3,800 screenings since the collaboration began. This oral head and neck exam is painless and quick, and open to everyone. Participants wearing dentures will be asked to remove them during the 10-minute exam.
• Prostate cancer screenings: Provided Aug. 19 and Aug. 20. Prostate screenings are recommended for men with average risk starting at age 50. African-American men and anyone with a brother, father or son who had prostate cancer before age 65 should begin getting screened for prostate cancer at age 45. Testing will involve a prostate specific antigen (PSA) blood test that involves taking a small amount of blood. A digital rectal exam also will be performed in the privacy of the Horses and Hope Cancer Screening Van to feel for any lumps, bumps or other abnormalities. The results of the PSA will be mailed about two weeks after the fair ends. The entire testing process takes approximately 20 minutes.
• Colon cancer screenings: Provided Aug. 21 through Aug. 27. Colon cancer screenings with FIT kits are available to anyone over 50 who has not had a colonoscopy within the past 10 years or a stool test in the past year. A free take-home kit will be available for men and women 50 and older and to younger participants who are cancer survivors or have a history of cancer in close relatives. The participant will complete stool collection at home and then mail it to UofL Hospital in special packaging provided.
• Cancer resources and Reiki demonstration from the M. Krista Loyd Resource Center��at the Brown Cancer Center: Provided Aug. 24. The Krista Loyd Center provides a peaceful environment for patients with cancer to learn, relax and heal emotionally. One service provided is the Japanese technique of Reiki for stress reduction and healing promotion. Personnel from the Loyd Center will demonstrate the technique.
• Stroke risk assessments and blood pressure screening:��Provided Aug. 22 and Aug. 26. The UofL Hospital Comprehensive Stroke Center was the first certified stroke center in Kentucky. Staff will provide free stroke risk assessment and blood pressure checks to fair-goers.

Areas receiving grants are pediatric cardiac regenerative medicine, pediatric surgery research, the Kosair Charities Pediatric Clinical Trials Unit, the UofL Autism Center at Kosair Charities, the Child and Adolescent Health Research Design and Support Unit, and the Kosair Children’s Hospital Research Institute.

“Research is vital to advancing the care we, as partners, can provide to children,” said Steven T. Hester, MD, MBA, system senior vice president and chief medical officer, Norton Healthcare. “The pediatric specialists at the University of Louisville are doing work that can help us provide even better care and, hopefully, cures.”

“We appreciate the funding provided by Norton Healthcare to further our work in understanding and ultimately curing diseases and conditions that affect children,” said Gregory C. Postel, MD, interim executive vice president for health affairs, University of Louisville. “At UofL, we have set an ambitious yet achievable agenda in pediatric research that will advance medical knowledge and provide novel and innovative treatments for the children of Kentuckiana and beyond.”

“We see firsthand the benefits that research provides to children,” said Thomas D. Kmetz, division president, Women’s and Children’s Services and Kosair Children’s Hospital. “Supporting this research agenda is incredibly important not just to children, but also in continuing to attract additional pediatric specialists to Louisville.”

The $1.25 million provides one year of funding to the six research areas:

• $100,000 for pediatric cardiac regenerative medicine, led by Bradley B. Keller, MD, for research focusing on identifying the biomechanical origins of congenital heart disease and the development of implantable engineered cardiac tissues for repair and restoration using patient-derived human pluripotent stem cells. The goal of these studies is to repair and regenerate damaged heart muscle as an alternative to cardiac transplantation.
• $100,000 for the pediatric surgery research lab, led by Mary E. Fallat, MD, to support research in surgical techniques and outcomes, trauma practices and necrotizing enterocolitis, a disease that affects mostly the intestine of premature infants where the wall of the intestine is invaded by bacteria that cause local infection and inflammation that can ultimately destroy the bowel wall. Research in this area directly impacts the care children and neonates receive when they need surgical services.
• $100,000 for the Kosair Charities Pediatric Clinical Research Unit, led by Janice E. Sullivan, MD, to support the unit’s medication, quality improvement and device clinical trials. The goal of this unit is to improve health care provided to children through development of new or improved treatment practices and evaluation and approval of medical devices or medications for children.
• $250,000 for the UofL Autism Center at Kosair Charities led by Gregory N. Barnes, MD, PhD, to support the Precision Medicine Initiative in Autism Spectrum Disorders. The goal of this study is to use a child’s DNA to develop individualized treatment approaches to better restore the function of neural circuits in the brain, thereby improving behavior and cognitive skills.
• $300,000 for the Child and Adolescent Health Research Design and Support Unit led by Charles R. Woods Jr., MD, to support research projects around overprescribing of psychiatric medications and antimicrobial agents in children, as well as improving data availability to frontline state workers in the foster care system. The goal of this research unit is to improve the effectiveness, quality, safety and delivery of health care and prevention/health promotion services to children.
• $400,000 for the Kosair Children’s Hospital Research Institute led by Lu Cai, MD, PhD, for support in research programs in the areas of diabetes- and obesity-related multi-organ diseases, including cardiovascular diseases, pulmonary diseases, neurobiological and carcinogenic susceptibility, molecular and cellular mechanisms and potential interventions. The focus of the institute is on basic and translational research, bringing these programs forward as quickly as possible from the laboratory bench to the patient’s bedside.

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