Project 3:
In year two and three of this project, patients with type 1 and type 2 diabetes will be recruited along with age matched controls. Patients will be initially characterized as to levels of autoreactive T cells using the assay developed in Project 1. Changes in the levels of autoreactive T cells in volunteers with type 1 diabetes will be monitored following BCG treatment.
Dr. Jerry Nadler – $370,000
University of Virgina, Diabetes and Hormone Center of Excellence
Charlottesville, VA
Clinical trial in type 1 diabetes
Lisofylline (LSF) is a novel small molecule immunomodulator that has been shown to be effective in halting autoimmune damage to pancreatic insulin producing beta cells in experimental models of type 1 diabetes. LSF does not impair the normal immune system but reduces the activity of a key cytokine called Interleukin-12 which plays a major role in leading to type 1 diabetes.
Recent evidence suggests that the body is attempting to regenerate insulin producing cells in type 1 diabetes but that the slow growth rate of beta cells and ongoing autoimmunity prevents the body from reversing diabetes. It has been recently shown in a publication that the combination of a beta growth factor called exendin-4 and LSF given by subcutaneous minipump can fully reverse established type 1 diabetes in the nod mouse model. Most animals have remained with normal blood sugar for up to 5 months after the removal of the medications. The exciting results recently presented at the ADA 2006 Scientific Sessions shows evidence of new beta cell regeneration in these treated mice.
LSF has been shown to be safe in human trials when given by the intravenous route but this is not a very practical way of using this medication for the majority of people with type 1 diabetes. The current funds will allow the reformulation and safety testing of LSF for subcutaneous delivery. It is anticipated that a clinical trial to test the safety and effectiveness of subcutaneous delivered LSF for treatment of type 1 diabetes will be initiated within a year.
LSF alone or in combination with a beta cell growth factor could offer a safe and effective way to help the body regenerate its own insulin producing cells resulting in reversal of type 1 diabetes.
2006 Iacocca Family Foundation Grants
Type 1 Diabetes Research – Four Projects
Dr. Lawrence Chan – $250,000
Baylor College of Medicine
Houston, TX
Induced islet neogenesis to reverse type 1 diabetes
Dr. Chan’s project proposes the use of gene therapy to produce new islet cells. In NOD mice they have successfully coaxed liver cells to become B cells. They have identified the gene for a protein whose duty is to instruct cells in early embryonic development to become pancreatic islet cells. This gene once delivered in the liver of diabetic mice coaxed liver cells to form pancreatic cells inside the liver producing insulin with all the same components and integrity of normal functioning beta cells.
Dr. Maja Maric – $104,000
Georgetown University Medical Center
Washington, DC
Identification of GILT-Specific Small Inhibitory Molecule
Dr. Maric’s proposal addresses the autoimmune attack at one of the earliest possible moments. Induction of anti-beta cell immune response is clearly initiated by breaking tolerance to islet antigens and the notion of targeting a very early step in the process of antigen processing is an area that is not being pursued. Ultimately the goal of the proposed project is to define small molecule inhibitors of GILT which, assuming that such an inhibitor can be targeted to those antigen processing cells where beta cell antigens are being captured and processed can be achieved, may suppress one of the earliest steps in the process of T cell activation.
Dr. Morris White – $410,000
Boston Children’s Hospital
Boston, MA
Identification of drugs that promote regeneration of islets
Dr. White believes that regeneration of pancreatic beta cells is possible, but is concerned there may not be sufficient regeneration to ensure insulin independence. This project is to identify molecules which can activate beta cells to increase expression of a key adapter molecule (IRS2) which functions in the insulin-signaling pathway. IRS2 mediates the insulin signal in non-beta cells, and is essential in beta cells to promote their growth, function, and survival.
Dr. Denise Faustman – $674,300
Massachusetts General Hospital
Boston, MA
Ongoing support of basic research in Dr. Denise Faustman’s lab at Massachusetts General Hospital.
Type 2 Diabetes – Intervention and Prevention - One Project
Harvard School of Public Health – $250,000
Boston, MA
Partnership with The Gilbert Foundation, California
This grant is to fund the development of a coast-to-coast initiative with leaders in the field of Childhood Obesity. The Coast to Coast Initiative to Prevent and Control Child Obesity (C2C) will implement, evaluate, and disseminate a cost-effective, integrated and sustainable approach to prevent and control obesity in elementary and middle school children nationwide. C2C will surround children with coordinated programs and policies to promote active, healthy lifestyles. C2C will include interventions that target three pivotal spheres of influence in children’s lives: Schools, Before- and After-school Programs, and Health Care. All intervention components will systematically involve parents and families, engage community partners, change food and activity policies and environments, and incorporate targeted media tools. C2C was conceived and will be carried out by a multi-disciplinary team of experts from the Harvard School of Public Health (HSPH), the University of California at Berkeley Center for Weight and Health (UCB-CWH), Mathematica Policy Research, Inc. (MPR), Samuels and Associates (SA), and WGBH, Boston’s Public Broadcasting Service station.
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