Type 1 diabetes (T1D) is associated with tremendous morbidity and premature mortality. Patients require multiple daily insulin injections throughout their lives as well as close monitoring of their diet and blood sugar levels to prevent disease associated complications. Unfortunately, there is presently no permanent cure for T1D. Whole pancreas or islet cell transplantation is available only to a very limited number of patients and necessitates potential lifelong immunosuppressive therapy. Granulocyte colony stimulating factor (G-CSF) has recently been shown to prevent T1D in the Non Obese Diabetic (NOD) mouse model of the disease. Those studies demonstrated that the benefits of G-CSF therapy are likely due to mobilization of T regulatory cells (Treg) from the bone marrow. Since Treg function is known to be diminished in patients with T1D, G- CSF may have the potential to dampen the autoimmune response by acting as a potent immunomodulator involving Treg stimulation. [Prior to the initiation of appropriately powered clinical trials of G-CSF, we must obtain a better understanding of the potential mechanisms associated with G-CSF stimulated mobilization of Treg in the T1D population. As such, we will perform a randomized, double-blinded, placebo controlled pilot study to document G-CSF's augmentation of Treg number and function in subjects with T1D. Twenty-one patients with persistent stimulated c-peptide 0.2 pmol/ml, will be randomized 2:1 (drug:placebo) to receive a 5 day course of daily subcutaneous G-CSF (10 mcg/kg/d) versus placebo]. Our primary goals will be to document the safety of G-CSF therapy and [characterize the mechanisms by which G-CSF augments] Treg number and function in the T1D population. Type 1 diabetes affects 1 in 300 people in the United States, requires lifelong administration of multiple daily insulin injections, frequently results in nerve, eye, kidney, and heart damage, and often results in a shortened lifespan. Type 1 diabetes is caused by an abnormal activation of the immune system that results in the destruction of the patients own insulin producing cells. This protocol will explore the potential of the drug Granulocyte Colony Stimulation Factor (GCSF) to stimulate immune cells that can potentially change the immune system and protect insulin producing cells from further damage.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1-EMNR-K (02))
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Spain, Lisa M
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University of Florida
Schools of Medicine
United States
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Haller, M J; Atkinson, M A; Wasserfall, C H et al. (2016) Mobilization without immune depletion fails to restore immunological tolerance or preserve beta cell function in recent onset type 1 diabetes. Clin Exp Immunol 183:350-7
Ize-Ludlow, Diego; Lightfoot, Yaima L; Parker, Matthew et al. (2011) Progressive erosion of ?-cell function precedes the onset of hyperglycemia in the NOD mouse model of type 1 diabetes. Diabetes 60:2086-91
Haller, Michael J; Atkinson, Mark A; Schatz, Desmond A (2010) Efforts to prevent and halt autoimmune beta cell destruction. Endocrinol Metab Clin North Am 39:527-39