Short Course G-CSF as Immunomodulatory Therapy for Type 1 Diabetes ? A Pilot Stud

描述（由申请人提供）：1型糖尿病（T1 D）与巨大的发病率和过早死亡率相关。患者一生中需要每天多次注射胰岛素，并密切监测其饮食和血糖水平，以预防疾病相关并发症。不幸的是，目前还没有T1 D的永久治愈方法。整个胰腺或胰岛细胞移植仅适用于非常有限数量的患者，并且需要潜在的终身免疫抑制治疗。粒细胞集落刺激因子（G-CSF）最近已被证明可以预防非肥胖糖尿病（NOD）小鼠模型中的T1 D。这些研究表明，G-CSF治疗的益处可能是由于骨髓中调节性T细胞（Treg）的动员。由于已知Treg功能在T1 D患者中减弱，因此G-CSF可能具有通过充当涉及Treg刺激的有效免疫调节剂来抑制自身免疫应答的潜力。[在启动适当的G-CSF临床试验之前，我们必须更好地了解与G-CSF刺激的T1 D人群中Treg动员相关的潜在机制。因此，我们将进行一项随机、双盲、安慰剂对照的初步研究，以记录G-CSF在T1 D受试者中增加Treg数量和功能。21例持续刺激C肽0.2 pmol/ml的患者将以2：1（药物：安慰剂）的比例随机接受5天疗程的每日皮下G-CSF（10 mcg/kg/d）与安慰剂]。我们的主要目标是记录G-CSF治疗的安全性，并[描述G-CSF增加T1 D人群Treg数量和功能的机制]。1型糖尿病在美国每300人中就有1人患病，需要终身每天多次注射胰岛素，经常导致神经、眼睛、肾脏和心脏损伤，并经常导致寿命缩短。1型糖尿病是由免疫系统的异常激活引起的，这导致患者自身的胰岛素产生细胞的破坏。该方案将探索药物粒细胞集落刺激因子（GCSF）刺激免疫细胞的潜力，这些免疫细胞可能会改变免疫系统并保护胰岛素产生细胞免受进一步损伤。

DESCRIPTION (provided by applicant): 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.