Chicago Comprehensive Sickle Cell Center: Basic & Translational Research Program

芝加哥综合镰状细胞中心:基础

基本信息

  • 批准号:
    7843553
  • 负责人:
  • 金额:
    --
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2008
  • 资助国家:
    美国
  • 起止时间:
    2008-06-18 至 2012-02-29
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): The CCSCC represents a collaborative consortium among three institutions, the University of Illinois at Chicago (UIC), the Children's Memorial Hospital (CMH), and the University of Chicago Comer Children's Hospital (UCH). The mission of the CCSCC is to improve the health, quality of life and longevity of persons afflicted with sickle cell disease through the triad of: 1) clinical and translational research designed to improve the treatment of sickle cell disease; 2) timely diagnosis and education of patients, their families and the community; and 3) provision of the highest quality medical care possible. The Center presents a thematic approach to the development of new therapies for sickle cell disease focused on the epigenetic regulation of gamma gene silencing. This approach is utilized in three proposed research projects. The Basic Science Project will study the role of DMA methylation in the mechanism of gene silencing. Studies will include the roles of polycomb group proteins, DMA methyltransferases (DNMT1), and histone H3 (Lys27) on DMA methylation. The Translation Research Project will focus on the effect novel DNMT1 inhibitors on DNA hypomethylation and induction of fetal hemoglobin. As part of the Translational Research Project, a new oral formulation of the FDA approved DNMT1 inhibitor decitabine will be tested in a Phase I clinical trial. The oral decitabine formulation will subsequently be compared to the gold standard, hydroxyurea, in a Phase ll/lll Inter- Center Collaborative Clinical Trial to determine whether decitabine is clinically superior. The Patient Services Research Project, CHOICES, will be an outcomes study to determine the effect of a computer-based, tailored, multimedia education program concerning reproductive options and consequences, on the reproductive intentions of patients with sickle disease and sickle cell trait. Overall responsibility for the management of the Center will reside in the Administrative Core. The Clinical Core will be responsible for the medical care provided to SCD patients at the three institutions, for participation in the Inter-Center Collaborative Clinical Trials conducted by the CSCC consortium, and for participation in the clinical aspects of the Translational Research Project. The Patient Services Core will provide supportive sickle cell focused services to SCD patients and their families, as well as to the lay and medical communities of the Chicago metropolitan area and the State of Illinois. Future research into SCD pathophysiology and therapy training young scientists will be enhanced through the Sickle Cell Scholar Program. INDIVIDUAL PROJECTS AND CORE UNITS: PROJECT 1: A PHASE ll/lll STUDY OF ORAL DECITABINE VERSUS HU TO TREAT SICKLE CELL DISEASE (Yogen Saunthararajah) DESCRIPTION (provided by applicant): Clinical and epidemiologic observations, supported by bench studies demonstrating that fetal hemoglobin (MbF) interferes with sickle hemoglobin (HbS) polymerization, have motivated attempts at sickle cell disease (SCD) modification through pharmacologic HbF reactivation. Since 1995, the agent used for this purpose and the standard of care for patients with symptomatic SCD has been hydroxyurea (HU). HU has been a great advance for SCD patients. However, it has a number of limitations, primarily the limited response rate and the limited magnitude of the HbF elevations. Decitabine, an inhibitor of DNA methylation, directly addresses a mechanism by which the gene responsible for producing HbF (gamma-globin) is silenced. Decitabine has produced a 100% response rate with large HbF elevations in all SCD patients treated to date. Therefore, decitabine offers the possibility of even greater and more wide-spread benefit for SCD, possibly with a similar or better toxicity profile than HU. This can ultimately only be determined through the conduct of a careful phasell/lll clinical trial. Within the time-frame of this RFA, it would be feasible to perform a randomized double-blind comparison of oral decitabine versus HU for symptomatic SCD. Hypotheses: Decitabine has a similar toxicitv profile (clinical adverse events. VDJ assay, ervthrocvte micronucleus assay) but is more effective than HU at (i) reducing crisis frequency: (ii) increasing markers associated with improved survival (HbF% and F-cell%): (iii) improving quality of life (QOU: (iv) reducing markers of hemolvsis (total Hb. reticulocvte count. LDH. bilirubin): (v) reducing a marker of pulmonary hypertension and increased mortality (BMP): (vi) reducing markers of coagulation pathway, inflammatory pathway and platelet activation (D-Dimers. C-Reactive Protein (CRP). soluble CD40-liaand (sCD40D): (vii) increasing ervthropoietin levels, a hormone with a poorly understood role in the anemia and responses to therapy in SCD. These hypotheses will be tested through completion of the following overall aim - to conduct a phase ll/lll randomized double-blind controlled trial of oral decitabine versus HU in 150 adults with SCD with crisis frequency as the primary end-point and the parameters underlined above as secondary end-points. The planned clinical and objective laboratory measurements provide a comprehensive read-out of the pathophysiological impact of HU and decitabine. The objective laboratory parameters that relate to different aspects of sickle cell pathophysiology such as chronic hemolysis, vaso-occlusion and coagulation pathway activation can be correlated with clinical outcomes to provide insight into the underlying patho-physiology of the various clinical manifestations of SCD and confirming or refuting the value of these objective laboratory parameters as surrogate clinical end-points. A potentially very important and potent SCD modifying agent with a novel mechanism of action will be pivotally and definitively assessed through completion of this trial. (End of Abstract)
描述(由申请人提供):

项目成果

期刊论文数量(16)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(5)
siDNMT1 increases γ-globin expression in chemical inducer of dimerization (CID)-dependent mouse βYAC bone marrow cells and in baboon erythroid progenitor cell cultures.
  • DOI:
    10.1016/j.exphem.2010.10.003
  • 发表时间:
    2011-01
  • 期刊:
  • 影响因子:
    2.6
  • 作者:
    Banzon, Virryan;Ibanez, Vinzon;Vaitkus, Kestis;Ruiz, Maria Armila;Peterson, Kenneth;DeSimmone, Joseph;Lavelle, Donald
  • 通讯作者:
    Lavelle, Donald
Adherence to a reproductive health intervention for young adults with sickle cell.
坚持对患有镰状细胞的年轻人进行生殖健康干预。
  • DOI:
    10.1097/jxx.0000000000000997
  • 发表时间:
    2024
  • 期刊:
  • 影响因子:
    1.2
  • 作者:
    Eades-Brown,NyemaT;Oguntoye,AnneO;Aldossary,Dalal;Ezenwa,MiriamO;Duckworth,Laurie;Dede,Duane;Johnson-Mallard,Versie;Yao,Yingwei;Gallo,Agatha;Wilkie,DianaJ
  • 通讯作者:
    Wilkie,DianaJ
Reproductive Health CHOICES for Young Adults with Sickle Cell Disease or Trait: Randomized Controlled Trial Outcomes over Two Years.
  • DOI:
    10.1007/s10897-015-9874-0
  • 发表时间:
    2016-04
  • 期刊:
  • 影响因子:
    1.9
  • 作者:
    Gallo AM;Wilkie DJ;Yao Y;Molokie RE;Stahl C;Hershberger PE;Zhao Z;Suarez ML;Johnson B;Angulo R;Carrasco J;Angulo V;Thompson AA
  • 通讯作者:
    Thompson AA
CpG methylation patterns and decitabine treatment response in acute myeloid leukemia cells and normal hematopoietic precursors.
  • DOI:
    10.1038/leu.2011.207
  • 发表时间:
    2012-02
  • 期刊:
  • 影响因子:
    11.4
  • 作者:
  • 通讯作者:
p53-Independent, normal stem cell sparing epigenetic differentiation therapy for myeloid and other malignancies.
  • DOI:
    10.1053/j.seminoncol.2011.11.011
  • 发表时间:
    2012-02
  • 期刊:
  • 影响因子:
    4
  • 作者:
    Saunthararajah Y;Triozzi P;Rini B;Singh A;Radivoyevitch T;Sekeres M;Advani A;Tiu R;Reu F;Kalaycio M;Copelan E;Hsi E;Lichtin A;Bolwell B
  • 通讯作者:
    Bolwell B
{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

JOSEPH DESIMONE其他文献

JOSEPH DESIMONE的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('JOSEPH DESIMONE', 18)}}的其他基金

A Novel, Non-Cytotoxic, Epigenetic Therapeutic for Sickle Cell Disease
镰状细胞病的新型非细胞毒性表观遗传疗法
  • 批准号:
    9755493
  • 财政年份:
    2017
  • 资助金额:
    --
  • 项目类别:
Improving HbF induction by inhibiting epigenetic target enzymes
通过抑制表观遗传靶酶改善 HbF 诱导
  • 批准号:
    8722603
  • 财政年份:
    2013
  • 资助金额:
    --
  • 项目类别:
Improving HbF induction by inhibiting epigenetic target enzymes
通过抑制表观遗传靶酶改善 HbF 诱导
  • 批准号:
    8467828
  • 财政年份:
    2013
  • 资助金额:
    --
  • 项目类别:
Chicago Comprehensive Sickle Cell Center: Basic & Translational Research Program
芝加哥综合镰状细胞中心:基础
  • 批准号:
    7640595
  • 财政年份:
    2008
  • 资助金额:
    --
  • 项目类别:
Chicago Sickle Cell Clinical Network
芝加哥镰状细胞临床网络
  • 批准号:
    7060130
  • 财政年份:
    2006
  • 资助金额:
    --
  • 项目类别:
Chicago Sickle Cell Clinical Network
芝加哥镰状细胞临床网络
  • 批准号:
    7407367
  • 财政年份:
    2006
  • 资助金额:
    --
  • 项目类别:
DNA METHYLATION, CHROMATIN AND GLOBIN GENE SILENCING
DNA 甲基化、染色质和珠蛋白基因沉默
  • 批准号:
    7349825
  • 财政年份:
    2006
  • 资助金额:
    --
  • 项目类别:
Chicago Sickle Cell Clinical Network
芝加哥镰状细胞临床网络
  • 批准号:
    7224149
  • 财政年份:
    2006
  • 资助金额:
    --
  • 项目类别:
DNA METHYLATION, CHROMATIN AND GLOBIN GENE SILENCING
DNA 甲基化、染色质和珠蛋白基因沉默
  • 批准号:
    7165383
  • 财政年份:
    2005
  • 资助金额:
    --
  • 项目类别:
DNA Methylation, Chromatin, and Globin Gene Silencing
DNA 甲基化、染色质和球蛋白基因沉默
  • 批准号:
    6739076
  • 财政年份:
    2003
  • 资助金额:
    --
  • 项目类别:

相似海外基金

SCTaware: A Comprehensive Program to Increase Sickle Cell Trait Knowledge and Awareness Among Parents of Infants Identified by Newborn Screening
SCTaware:一项综合计划,旨在提高新生儿筛查发现的婴儿父母对镰状细胞性状的了解和认识
  • 批准号:
    9915969
  • 财政年份:
    2019
  • 资助金额:
    --
  • 项目类别:
The Delaware Comprehensive Sickle Cell Research Center
特拉华州综合镰状细胞研究中心
  • 批准号:
    9056602
  • 财政年份:
    2014
  • 资助金额:
    --
  • 项目类别:
The Delaware Comprehensive Sickle Cell Research Center
特拉华州综合镰状细胞研究中心
  • 批准号:
    8624777
  • 财政年份:
    2014
  • 资助金额:
    --
  • 项目类别:
The Delaware Comprehensive Sickle Cell Research Center
特拉华州综合镰状细胞研究中心
  • 批准号:
    8898133
  • 财政年份:
    2014
  • 资助金额:
    --
  • 项目类别:
The Delaware Comprehensive Sickle Cell Research Center
特拉华州综合镰状细胞研究中心
  • 批准号:
    10463769
  • 财政年份:
    2014
  • 资助金额:
    --
  • 项目类别:
The Delaware Comprehensive Sickle Cell Research Center
特拉华州综合镰状细胞研究中心
  • 批准号:
    10664915
  • 财政年份:
    2014
  • 资助金额:
    --
  • 项目类别:
The Delaware Comprehensive Sickle Cell Research Center
特拉华州综合镰状细胞研究中心
  • 批准号:
    9274317
  • 财政年份:
    2014
  • 资助金额:
    --
  • 项目类别:
The Delaware Comprehensive Sickle Cell Research Center
特拉华州综合镰状细胞研究中心
  • 批准号:
    10271040
  • 财政年份:
    2014
  • 资助金额:
    --
  • 项目类别:
Washington Area Comprehensive Sickle Cell Center
华盛顿地区综合镰状细胞中心
  • 批准号:
    7821241
  • 财政年份:
    2008
  • 资助金额:
    --
  • 项目类别:
Univ. of Miami Comprehensive Sickle Cell Center: Basic & Translational Research
大学。
  • 批准号:
    7821226
  • 财政年份:
    2008
  • 资助金额:
    --
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了