University of Michigan Autoimmunity Center of Excellence, Clinical Research Progr

密歇根大学自身免疫卓越中心临床研究项目

基本信息

批准号：
9480038
负责人：
David Alan Fox
金额：
$ 7.75万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-05-01 至 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9480038
关键词：
Advisory Committees Autoimmune Diabetes Autoimmune Diseases Autoimmunity Award Boston Cells Characteristics Clinical Clinical Investigator Clinical Research Clinical Trials Clinical effectiveness Core Facility Development Diabetes Mellitus Disease Disease Pathway Doctor of Philosophy Epidemiology Faculty Fibrosis Fostering Foxes Funding Grant Host Defense Human Immune Immune Cell Activation Immune system Immunologics Immunosuppressive Agents Link Lymphocyte Mediating Michigan Multiple Sclerosis National Institute of Allergy and Infectious Disease Neuraxis Organ Pathogenesis Pathogenicity Patients Pharmaceutical Preparations Play Process Reagent Recovery Research Personnel Research Project Grants Rheumatoid Arthritis Role Scleroderma Secondary Progressive Multiple Sclerosis Skin Sphingosine-1-Phosphate Receptor Systemic Scleroderma T-Lymphocyte Translational Research United States National Institutes of Health Universities Work Yang autoimmune thyroid disease autoreactive T cell clinical predictors cytotoxic effective therapy experience individual patient insight multidisciplinary novel novel marker novel strategies phase 3 study phase III trial programs repaired tissue biomarkers translational scientist trial design

项目摘要

DESCRIPTION (provided by applicant): This Clinical ACE application is driven by the hypothesis that organ-targeted autoimmune diseases are mediated by unique pathogenic interactions between cells of the immune system and parenchymal cells of the target organ, which play both afferent and efferent roles in disease initiation and target organ destruction. By understanding these disease-specific processes, new avenues to disease-specific treatment should come into view, along with novel biomarkers that reflect disease-specific interactions between lymphocytes and cells of the target organ. This hypothesis underlies the three proposed projects of this Clinical ACE. The Primary Clinical Project: "Mechanistic studies of Phase III trial with BAF312 in Secondary Progressive Multiple Sclerosis", led by Yang Mao-Draayer, PhD, MD and Benjamin M. Segal, MD, will study the mechanisms of clinical benefit of a novel sphingosine-1-phosphate receptor modulator, focusing both on pathogenic T cell autoreactivity characteristic of MS, and on the ability of the damaged central nervous system to initiate repair and recovery from immune attack. The Alternate Clinical Project: "Mechanistic studies of treatment of systemic sclerosis with Abatacept", led by Dinesh Khanna, MD, MS, with co-investigator David A Fox, MD, Robert Lafyatis, MD (Boston U), and Michael Whitfield, PhD (Dartmouth), will assess the effects of T cell co-stimulation blockade in scleroderema on both immune cell activation, and biomarkers of tissue damage and fibrosis in the skin. The Collaborative Project: "Role of organ-specific parenchymal cells in human organ-targeted autoimmune diseases", led by Massimo Pietropaolo, MD, with co-investigators David A. Fox, MD, Roberto Gianani, MD, and Terry J. Smith, MD, will study target organ phenomena potentially involved in the initiation of autoimmune diabetes, rheumatoid arthritis and autoimmune thyroid disease, three conditions that cluster epidemiologically. The Administrative Core and overall project will be led by David A. Fox, MD, who has two decades of experience in directing multidisciplinary NIH-funded center grant awards. RELEVANCE: The University of Michigan Clinical ACE, by linking experienced investigators in multiple sclerosis, scleroderma, diabetes, rheumatoid arthritis and autoimmune thyroid disease in the exploration of related yet distinct mechanisms of target organ damage in these conditions, will develop new approaches to understanding and treating human autoimmunity.

描述（由申请人提供）：该临床 ACE 申请是由以下假设驱动的：器官靶向自身免疫性疾病是由免疫系统细胞和靶器官实质细胞之间独特的致病性相互作用介导的，这些细胞在免疫系统中发挥传入和传出作用疾病发生和靶器官破坏。通过了解这些疾病特异性过程，应该可以看到疾病特异性治疗的新途径，以及反映淋巴细胞和靶器官细胞之间疾病特异性相互作用的新生物标志物。这一假设是本临床 ACE 的三个拟议项目的基础。主要临床项目：“BAF312 治疗继发性进行性多发性硬化症 III 期试验的机制研究”，由医学博士 Yang Mao-Draayer 和医学博士 Benjamin M. Segal 领导，将研究一种新型鞘氨醇的临床获益机制-1-磷酸受体调节剂，既关注 MS 的致病性 T 细胞自身反应特征，又关注受损中枢神经系统启动修复和从免疫攻击中恢复的能力。替代临床项目：“阿巴西普治疗系统性硬化症的机制研究”，由 Dinesh Khanna（医学博士、理学硕士）领导，联合研究员 David A Fox（医学博士）、Robert Lafyatis（医学博士）（波士顿大学）和 Michael Whitfield（博士）（达特茅斯）将评估硬皮病中 T 细胞共刺激阻断对免疫细胞激活以及皮肤组织损伤和纤维化生物标志物的影响。合作项目：“器官特异性实质细胞在人类器官靶向自身免疫性疾病中的作用”，由医学博士 Massimo Pietropaolo 领导，共同研究人员包括医学博士 David A. Fox、医学博士 Roberto Gianani 和 Terry J. Smith，医学博士将研究可能与自身免疫性糖尿病、类风湿性关节炎和自身免疫性甲状腺疾病的发生有关的靶器官现象，这三种疾病在流行病学上属于聚集性疾病。行政核心和整个项目将由医学博士 David A. Fox 领导，他在指导 NIH 资助的多学科中心拨款方面拥有二十年的经验。相关性：密歇根大学临床 ACE 将联合多发性硬化症、硬皮病、糖尿病、类风湿性关节炎和自身免疫性甲状腺疾病方面经验丰富的研究人员，探索这些疾病中靶器官损伤的相关但独特的机制，将开发新的方法来理解和治疗治疗人类自身免疫。

项目成果

期刊论文数量（23）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Dimethyl fumarate treatment shifts the immune environment toward an anti-inflammatory cell profile while maintaining protective humoral immunity.

DOI：
10.1177/1352458520937282
发表时间：
2021-05
期刊：
Multiple sclerosis (Houndmills, Basingstoke, England)
影响因子：
0
作者：
Longbrake EE;Mao-Draayer Y;Cascione M;Zielinski T;Bame E;Brassat D;Chen C;Kapadia S;Mendoza JP;Miller C;Parks B;Xing D;Robertson D
通讯作者：
Robertson D

Dimethyl Fumarate Selectively Reduces Memory T Cells and Shifts the Balance between Th1/Th17 and Th2 in Multiple Sclerosis Patients.

DOI：
10.4049/jimmunol.1601532
发表时间：
2017-04-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
0
作者：
Wu Q;Wang Q;Mao G;Dowling CA;Lundy SK;Mao-Draayer Y
通讯作者：
Mao-Draayer Y

Characteristics of Progressive Multifocal Leukoencephalopathy Associated With Sarcoidosis Without Therapeutic Immune Suppression.

与结节病相关的进行性多灶性白质脑病的特征，无需治疗性免疫抑制。

DOI：
10.1001/jamaneurol.2023.0841
发表时间：
2023
期刊：
JAMA neurology
影响因子：
29
作者：
McEntire,CalebRS;Fletcher,Anita;Toledano,Michel;Epstein,Samantha;White,Emily;Tan,CSabrina;Mao-Draayer,Yang;Banks,SamanthaA;Aksamit,AllenJ;Gelfand,JeffreyM;Thakur,KiranT;Anand,Pria;Cortese,Irene;Bhattacharyya,Shamik
通讯作者：
Bhattacharyya,Shamik

Safety and Immune Effects of Blocking CD40 Ligand in Multiple Sclerosis.

DOI：
10.1212/nxi.0000000000001096
发表时间：
2021-11
期刊：
Neurology(R) neuroimmunology & neuroinflammation
影响因子：
0
作者：
Fadul CE;Mao-Draayer Y;Ryan KA;Noelle RJ;Wishart HA;Channon JY;Kasper IR;Oliver B;Mielcarz DW;Kasper LH
通讯作者：
Kasper LH

Synovial cellular and molecular markers in rheumatoid arthritis.