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(T1D)与巨大的发病率和过早死亡有关。患者一生中需要每天多次注射胰岛素，并密切监测他们的饮食和血糖水平，以防止与疾病相关的并发症。不幸的是，目前还没有根治T1D的方法。全胰腺或胰岛细胞移植只适用于数量非常有限的患者，需要进行潜在的终身免疫抑制治疗。粒细胞集落刺激因子(G-CSF)最近被证明可以在非肥胖糖尿病(NOD)小鼠模型中预防T1D。这些研究表明，G-CSF治疗的好处可能是由于动员了骨髓中的T调节细胞(Treg)。由于已知T1D患者的Treg功能减弱，G-CSF可能作为一种涉及Treg刺激的有效免疫调节剂而抑制自身免疫反应。在启动适当动力的G-CSF临床试验之前，我们必须更好地了解与G-CSF刺激的T1D人群Treg动员相关的潜在机制。因此，我们将进行一项随机、双盲、安慰剂对照的先导性研究，以证明G-CSF对T1D患者Treg数量和功能的增强。21名持续刺激C-肽浓度为0.2pmol/ml的患者将随机分为2：1(药物：安慰剂)和安慰剂，接受每日皮下G-CSF(10微克/公斤/天)和安慰剂5天的疗程。我们的主要目标将是证明G-CSF治疗的安全性，并[描述G-CSF增强的机制]T1D人群中的Treg数量和功能。在美国，每300人中就有1人患有1型糖尿病，需要终生接受多次每日胰岛素注射，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，导致患者自身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害。

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.