Treatment/Type 1 Diabetes/hGAD65 Altered Peptide Ligand

治疗/1 型糖尿病/hGAD65 改变的肽配体

• 批准号: 6665526
• 负责人: GERALD T NEPOM
• 金额: $ 43.88万
• 依托单位: BENAROYA RESEARCH INST AT VIRGINIA MASON
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6665526
• 关键词: T cell receptor; T lymphocyte; autoantigens; cell proliferation; cellular immunity; clinical research; cross immunity; diabetes mellitus therapy; gene expression; genetically modified animals; glutamate decarboxylase; helper T lymphocyte; histocompatibility antigens; human subject; human therapy evaluation; immunomodulators; immunotherapy; insulin; insulin dependent diabetes mellitus; laboratory mouse; ligands; mass spectrometry; pancreatic islets; patient oriented research; peptides

DESCRIPTION (provided by applicant): Key immunologic and clinical safety issues will be directly evaluated in concert with in vitro analysis of human T cell clones and in vivo studies in a murine model. In the first phase (R21) of this application, milestones for APL specificity, sensitivity, and activity on polyclonal T cells will be addressed by both structural and mechanistic approaches. Antigenic cross-reactivity with native hGAD65 will be rigorously evaluated in HLA-DR4 transgenic mice to meet milestones for advancing to the second phase (R33) of this project. After successful completion of these milestones, we propose to submit an IND and clinical trial protocol for a phase I study in patients. Safety criteria for this phase of the application include immunologic, metabolic, and neurologic outcomes. Novel HLA-GAD tetramer assays will be used to evaluate immunologic perturbations of antigen-specific CD4+ T cells during therapeutic APL administration. This research plan combines the expertise of Dr. G. Nepom's immunology laboratory with the clinical research expertise of Dr. C. Greenbaum in a collaborative partnership for comprehensive evaluation of a potential new diabetes therapy. This team of basic and clinical scientists at VMRC holds joint weekly meetings and is well suited to expeditiously move from feasibility studies to development and clinical trials.

描述（由申请人提供）：

项目成果

Trying to Conceive After an Early Pregnancy Loss: An Assessment on How Long Couples Should Wait.

• DOI: 10.1097/aog.0000000000001159
• 发表时间: 2016-02
• 期刊: Obstetrics and gynecology
• 影响因子: 7.2
• 作者: Schliep KC;Mitchell EM;Mumford SL;Radin RG;Zarek SM;Sjaarda L;Schisterman EF
• 通讯作者: Schisterman EF

The effect of a very short interpregnancy interval and pregnancy outcomes following a previous pregnancy loss.

• DOI: 10.1016/j.ajog.2014.09.020
• 发表时间: 2015-03
• 期刊: AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
• 影响因子: 9.8
• 作者: Wong, Luchin F.;Schliep, Karen C.;Silver, Robert M.;Mumford, Sunni L.;Perkins, Neil J.;Ye, Aijun;Galai, Noya;Wactawski-Wende, Jean;Lynch, Anne M.;Townsend, Janet M.;Faraggi, David;Schisterman, Enrique F.
• 通讯作者: Schisterman, Enrique F.