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2019
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Cure for Type 1 Diabetes
A PROGRAM FOR THE CURE OF TYPE 1 DIABETES USING A GENERIC DRUG: PHASE II
Researcher:
Denise L. Faustman, MD, PhD., Associate Professor
Harvard Medical School and Director Immunobiology Laboratory
Massachusetts General Hospital
Charlestown, MA
Purpose:
In August 2012, results of the Phase I trial showed that the pancreas of long-term diabetics was able to transiently make insulin after two doses of the Bacillus Camlette-Guerin (BCG) vaccine. In 2018 a follow up report on a total of 232 participants both treated and untreated with BCG, published in the journal Vaccines, showed positive results in lowering blood sugars in subjects with type 1 diabetes to almost normal levels while also reducing the amount of insulin needed about one-third after 5 to 8 years from the initial treatment with the BCG vaccine without any reports of severe hypoglycemia. The 2015 FDA approved Phase II clinical trial, which is now fully enrolled with 150 participants with long-term type 1 diabetes, will determine the dose and frequency of doses required to reverse type 1 diabetes. It is still necessary to obtain funding to track these patients for an additional five years with the ultimate goal of bringing BCG to market as an approved treatment for type 1 diabetes. Five additional clinic trials with BCG/placebo to over 200 subjects are currently ongoing.
DEVELOPMENT OF A MACROCELL (ISLET) ENCAPSULATION DEVICE TO CURE DIABETES
Researcher:
Douglas Sobel, MD
Professor of Pediatrics, Chief Pediatric Endocrinology
Georgetown University
Washington, DC
Purpose:
Although islet transplantation is a promising approach to cure type 1 diabetes, the need for toxic drug therapy impedes its use. The subcutaneous administration of a macroencapsulated cell device could safely cure diabetes without immunotherapy but the sensitivity of human islets to the low oxygen environment in the subcutaneous space has been a major obstacle. Dr. Sobel’s lab has constructed a Membrane Device which, when loaded with MIN (mouse insulin secreting cells), and transplanted subcutaneously, cures diabetes in mice. Further, this implanted Device loaded with even human islets and growth-factor cures diabetes in nude mice. This study proposes to improve the Device by determining: (1) which membrane materials best support MIN cell growth in vitro and in vivo (2) which of these membrane devices best cures diabetic mice (3) which device also prevents the rejection of transplanted human islets. This work will be a major step towards safely curing people of diabetes through islet transplantation.
diabetes prevention
LONG-TERM TRAJECTORY OF EARLY VERSUS LATE ONSET TYPE 2 DIABETES: THE CORONARY ARTERY RISK DEVELOPMENT IN YOUNG ADULTS (CARDIA)
Researcher:
EunSeok Cha, Ph.D., MPH, MSN, CDE, RN
Assistant Professor
Emory University Nell Hodson Woodruff School of Nursing
Atlanta, GA
Purpose:
Individuals with early-onset type 2 diabetes (before age 40) have much greater risks of developing chronic diabetes complications compared to those with late-onset diabetes (after age 40), even if they have had diabetes the same length of time. However, current screening, prevention, and treatment guidelines for early-onset are normed for those of late onset. Using data from a landmark observational study, the Coronary Artery Risk Development in Young Adults, this study aims to identify possible differences in the predictors of developing pre-diabetes and type 2 diabetes between early and late onset type 2 diabetes groups. Contributing factors to generate different progression mechanisms in early and late-onset diabetes will be examined. Findings will provide information to increase the precision of diabetes prevention, identification, and care for individuals at risk for and with early onset type 2 diabetes.
IDENTIFICATION OF EARLY CIRCULATING DIAGNOSTIC AND PROGNOSTIC BIOMARKERS FOR TYPE 2 DIABETES MELLITUS
Researcher:
Sandra Lobo, Ph.D.
Director, Biomedical Research Institute
Western Connecticut Health Network
Danbury, CT
Purpose:
Type 2 diabetes is a metabolic disease and a growing global epidemic. Current tests diagnose patients with type 2 diabetes at a late stage when treatment is problematic due to severe metabolic imbalances in these patients. Treatment goals involve tight control of glucose levels to delay the progression of type 2 diabetes and prevent the complications known to significantly decrease the quality of life. Current therapies would be more effective when used in patients at high risk for developing type 2 diabetes before the metabolic imbalances set in. This study will help identify early biomarkers circulating in the blood of patients that affect metabolic function placing them at risk of developing type 2 diabetes, prior to its onset. These patients will benefit from lifestyle and/or drug treatment to prevent developing type 2 diabetes rather than delay its progression.
COMPLEMENTARY / NUTRITION RESEARCH
DETERMINE THE ROLE OF VITAMIN A IN THE DEVELOPMENT OF TYPE 2 DIABETES IN ZUCKER DIABETIC FATTY RATS
Researcher:
Guoxun Chen, Ph.D.
Associate Professor, Dept. of Nutrition
The University of Tennessee, Knoxville
Knoxville, TN
Purpose:
The rise of obese population in the U.S. indicates more people with type 2 diabetes in the future, which can be attributed to genetic and nutritional factors. For humans without genetic long-term over-nutrition, excessive intakes of macronutrients (carbohydrates, fat and proteins) for energy, and micronutrients (vitamins and minerals) for metabolic regulation, play a key role in the process. Whether micronutrients such as Vitamin A (VA) play a role in type 2 diabetes development is still an open question. The principal investigator of this proposal has investigated the roles of VA in the regulation of sugar and fat metabolism since 2006. The results show that VA status regulates obesity development and fuel metabolism in Zucker fatty rats. This study will determine whether dietary VA status contributes to type 2 diabetes development in Zucker diabetic fatty rats, a model of type 2 diabetes due to over-nutrition.
EFFECTS OF FATTY ACIDS ON THE BRAIN’S REGULATION OF GLUCOSE METABOLISM
Researcher:
Meredith Hawkins, MD
Professor, Dept. of Medicine (Endocrinology)
Albert Einstein College of Medicine
Bronx, NY
Purpose:
Patients with type 2 diabetes have inappropriately high blood sugar levels, which is predominately produced by the liver. There is evidence in humans and rats that the brain normally regulates sugar production by the liver. However, this regulation is lost in people with type 2 diabetes. Dr. Hawkins’ lab hypothesizes that lowering circulating levels of a type of fat found in the body (free fatty acids) could restore this regulation and improve the brain’s ability to control sugar levels. Patients with type 2 diabetes will be studied before and after normalizing their free fatty acids levels with vitamin B3, to determine whether the brain’s impaired ability to regulate blood sugar can be reversed. Together, these studies will determine whether it is possible to restore the brain’s regulation of blood sugar in type 2 diabetes. These studies are likely to provide novel therapeutic target for controlling blood sugar levels in type 2 diabetes.
PROTECTIVE ROLE OF DIETARY OMEGA-3 FATTY ACIDS ON RESOLUTION OF INFLAMMATION IN THE DIABETIC BRAIN
Researcher:
Kevin W. Huggins, Ph.D.
Associate Professor
Auburn University
Auburn, AL
Purpose:
Type 2 diabetes is associated with neurodegeneration leading to cognitive deficits. The mechanism(s) underlying this diabetes-associated cognitive decline is poorly understood but may be related to an increase in diabetes-induced inflammation in the brain. Increased consumption of omega-3 polyunsaturated fatty acids (PUFA) from cold water fish and fish oils have been associated with a decreased risk of diabetes and cognitive decline associated with diabetes. This effect may be related to the anti-inflammatory properties of omega-3 PUFA. Specifically, increased brain omega-3 PUFA increases the production of pro-resolving lipid mediators which decrease inflammation. The goal of this study is to determine the role of omega-3 derived pro-resolving lipid mediators on inflammation in the brain of diabetic mice.
HIGH FAT DIET-INDUCED DIABETES IS ABOLISHED BY COMBINED GENISTEIN AND EXERCISE TREATMENT: IDENTIFYING THE MECHANISMS
Researcher:
Layla Al-Nakkash, Ph.D.
Professor of Physiology
Midwestern University
Glendale, AZ
Purpose:
Clinically, for those millions of individuals that have type 2 diabetes or obesity-related diabetes, the impact to overall health is significant. These disorders are complex and provision of effective treatments is also difficult. Dr. Al-Nakkash’s lab will use a mouse model of diabetic obesity, therefore mice will be given a “Western diet” which means they will feed them a high amount of fat for a fairly long time period. They will examine the effects of either consuming genistein ( a naturally occurring compound found in soy) or participating in regular moderate exercise (or both) on key markers of gut and metabolic health. The lab will examine the effects of sex (do males and females respond differently). They will use standard laboratory techniques to assess both gut and overall health in this model of type 2 diabetes. These studies will help our understanding of how exercise and soy can be of benefit to diabetics.
PREVENTION OF AMYLIN AMYLOIDOSIS IN TYPE 2 DIABETES BY BOTANICAL BAICALEIN
Researcher:
Bin Xu, Ph.D., Assistant Professor
Virginia Polytechnic Institute and State University
Blacksburg, VA
Purpose:
The goal of this project is to investigate the novel functions of a natural product, baicalein, in the prevention and treatment of diabetes and its complications. Due to a rapidly aging population and the modern sedentary lifestyle, type 2 diabetes and related neurodegeneration are reaching epidemic proportions and they are among the fastest growing diseases in America and worldwide. Currently, there is no known cure for these diseases. One potential molecule link between these two diseases is a molecule call amylin. Excessive secretion of this molecule in type 2 diabetes patients can lead to the formation of toxic aggregates, which can deposit in the pancreas and in other organs such as the brain and cause damages in these tissues. The researchers discovered that baicalein potently inhibits amylin aggregation and reduces amylin-induced toxicity. The researchers will determine how baicalein can inhibit amyloid formation and test how effective baicalein is in a diabetic animal model.
TREATING AND PREVENTING COMPLICATIONS
NICOTINAMIDE RIBOSIDE PREVENTION OF NEUROPATHY IN TYPE 1 DIABETES
Researcher:
James Russell, MD, MBchB, MS, FACP, FRCP
Professor Dept. of Neurology, Anatomy and Neurobiology
Vice Chair for Research, Dept. of Neurology
University of Maryland School of Medicine
Baltimore, MD
Purpose:
Neuropathy eventually affects over 60% of patients with type 1 diabetes. Improved glycemic control is associated with amelioration of diabetic neuropathy but there is no treatment that prevents neuropathy developing or progressing. Neuropathy in type 1 diabetes may be associated with a decrease in tissue levels of nicotinamide adenine dinucleotide (NAD). Deficiency of NAD can affect critical pathways that protect cellular metabolic function in the peripheral nerve against oxidative and glutaminergic injury. A safe, orally bioavailable therapy is needed that can be taken chronically to prevent neuropathy developing in young adults. Dr. Russell’s lab will test if dietary nicotinamide ribosome (NR), which repletes NAD levels, prevents neuropathy in an animal model of type 1 diabetes. Dr. Russell’s lab obtained an FDA IND for NR treatment in human type 2 diabetic neuropathy. However, they need to determine if NR can prevent neuropathy in type 1 diabetes and if the effect can be sustained.
TESTING OF NEW INTERVENTION TO TREAT TYPE 1 DIABETES INDUCED KIDNEY FAILURE
Researcher:
Kai Y. Xu, Assoc. Professor
University of Maryland
Baltimore, MD
Purpose:
Type 1 diabetes causes kidney failure in which the kidneys are no longer able to remove waste from the body. (Na+and K+)-ATPase (NKA) is found in large amounts of kidney and plays a crucial role in kidney function. Studies have shown that significant reduction of the NKA activity is strongly associated with type 1 diabetes-induced kidney failure, indicating that NKA activity is an essential basis for kidney function. Dr. Xu has developed a NKA activator which markedly increases NKA activity. Dr. Xu hypothesizes that protecting kidney NKA activity through the NKA activator may offer a new disease modifying intervention to prevent and treat type 1 diabetes-induced kidney failure. The purpose of this study is to test whether the NKA activator protects kidney function against the progression of kidney failure. If the hypothesis is supported by the experimental results, this study will transform basic research findings into medical technology for better treatment of type 1diabetes-induced kidney failure.
ISLET CELL RESEARCH
BIOPRINTING OF ENGINEERED PANCREATIC ISLETS INTO A PERFUSION BED
Researcher:
Ibrahim T. Ozbolat, Ph.D.
Associate Professor
Penn State University
University Park, PA
Purpose:
In Dr. Ozbolat’s original project, he aimed to bioprint pre-vascularized pancreatic islets made of mouse insulinoma cells and rat heart microvascular endothelial cells into a perfusion bed in order to create a perfusable platform for microcirculation of the engineered islets. With additional funding, Dr. Ozbolat will further extend these efforts and utilize human cells, where human beta cells and endothelial cells derived from human adipose-derived stem cells will be used to form pancreatic islets. Pre-vascularized pancreatic islets will be bioprinted into the perfusion bed and this study will test the hypothesis that perfused human pancreatic tissue constructs improve islet viability and function through performing LIVE/DEAD assays, immunostaining and glucose challenging tests.