CLINICAL TRIAL: PHASE I/II TRIAL USING CYCLOPHOSPHAMIDE AND LOW-DOSE IL-2 TO IND

临床试验：使用环磷酰胺和低剂量 IL-2 进行 IND 的 I/II 期试验

• 批准号: 8166775
• 负责人: Stanley H. Appel
• 金额: $ 0.08万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8166775
• 关键词: Amyotrophic Lateral Sclerosis; Brain; Cells; Clinical Trials; Collaborations; Computer Retrieval of Information on Scientific Projects Database; Cyclophosphamide; Deterioration; Diagnosis; Disease; Disease Progression; Dose; FDA approved; Funding; Goals; Grant; Human; IL2 gene; Immune response; Immune system; Institution; Interleukin-2; Intravenous; Metastatic Melanoma; Motor Neurons; Mus; Muscle; Muscle Weakness; Pathogenesis; Patients; Phase; Play; Population; Regulatory T-Lymphocyte; Relative (related person); Renal carcinoma; Research; Research Personnel; Resources; Respiratory Failure; Respiratory Muscles; Role; Source; Spinal Cord; Stem cell transplant; T-Cell Depletion; Time; Transplantation; United States National Institutes of Health; effective therapy; gene therapy; graft vs host reaction; mouse model; mutant; nervous system disorder; wasting

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. ALS is a progressive neurological disease which is usually fatal, causing increasing weakness and wasting of the muscles as the motor neurons of the brain and spinal cord die. This progressive deterioration eventually leads to respiratory failure due to respiratory muscle weakness. The cause of ALS is not known but recent evidence suggests that the immune system plays a significant role in the pathogenesis of ALS. In the mutant SOD1 mouse model of ALS we have documented a relative depletion of T cells, primarily T reg cells, associated with an accelerated disease progression and decreased survival. Transplantation into these mice with T reg cells slows disease progression and significantly prolongs survival. Our preliminary human ALS studies have indicated that patients that decline more rapidly have fewer T reg cells than slow progressors. The goal of this study is to increase the Treg cell population in ALS patients. The study will be conducted in collaboration with Dr. Malcolm Brenner, Chair of Cell and Gene Therapy. Dr. Brenner has carried out numerous studies using IL-2 to increase a patient''s own population of T reg cells. Patients will be given a single dose of intravenous cyclophosphamide followed by administration of IL-2, given 3 times a week for 12 weeks to repopulate the immune system with Treg cells. Each subject will be followed for one year to assess their immune response and progression of disease. This therapy has been successfully employed in minimizing graft-versus-host reactions and is an FDA-approved treatment for metastatic melanoma and kidney cancer in humans following stem cell transplantation. Although our goal is to slow disease progression and prolong survival, there is no evidence to indicate that this approach will definitely slow disease progression. However, there is presently no effective therapy for patients with ALS; and at the very least, we will enhance our understanding of the potential role of the immune system in disease pathogenesis. The use of cyclophosphamide followed by a low dose IL2 administration in patients with amyotrophic lateral sclerosis (ALS) will delay disease progression for patients diagnosed with ALS.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 ALS是一种进行性神经系统疾病，通常是致命的，随着脑部和脊髓的运动神经元死亡，肌肉会增加肌肉的虚弱和浪费。这种进行性恶化最终导致呼吸道肌肉无力导致呼吸衰竭。 ALS的原因尚不清楚，但最近的证据表明，免疫系统在ALS的发病机理中起着重要作用。在ALS的突变体SOD1小鼠模型中，我们记录了T细胞的相对耗竭，主要是与加速疾病进展和生存降低相关的T Reg细胞。带有T Reg细胞的小鼠移植到这些小鼠中减慢疾病的进展并显着延长生存率。我们的初步人类ALS研究表明，与慢速进步者相比，下降的患者的T型细胞更快。这项研究的目的是增加ALS患者的Treg细胞群体。该研究将与细胞和基因治疗主席Malcolm Brenner博士合作进行。 Brenner博士使用IL-2进行了大量研究，以增加患者自身的T Reg细胞群体。将给予患者单剂量的静脉注射环磷有剂，然后给予IL-2，每周3次，持续12周，用Treg细胞重新填充免疫系统。每位受试者将遵循一年来评估其免疫反应和疾病进展。该疗法已成功地用于最大程度地减少移植物抗宿主反应，是一种经过FDA批准的治疗，用于在干细胞移植后针对人类的转移性黑色素瘤和肾癌。 尽管我们的目标是减慢疾病进展并延长生存期，但没有证据表明这种方法肯定会慢慢疾病的进展。但是，目前尚无针对ALS患者的有效疗法。至少，我们将增强对免疫系统在疾病发病机理中潜在作用的理解。 在肌萎缩性侧索硬化症患者中使用环磷酰胺，然后使用低剂量IL2给药，这将延迟诊断为ALS患者的疾病进展。