Efficacy of combination therapy in the Cynomolgus macaque model
联合治疗在食蟹猴模型中的疗效
基本信息
- 批准号:9750609
- 负责人:
- 金额:$ 79.98万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:AddressAnimal ModelAntibioticsAutopsyBiological AssayBiological ModelsCellsClinicalClinical DataClinical TrialsCombined Modality TherapyComplexCoupledDataDiseaseDisease ProgressionDoseDrug CombinationsDrug KineticsDrug resistanceFiberGranulomaHumanImageImaging technologyIndividualInfectionLesionMacacaMapsMeasuresMetabolicMethodsModelingMonitorMorbidity - disease rateMusMycobacterium tuberculosisOutcomePathologyPharmaceutical PreparationsPharmacotherapyPositron-Emission TomographyPreclinical TestingPublicationsRegimenResistanceResolutionTechnologyTestingTimeToxic effectTranslationsTuberculosisWorkX-Ray Computed Tomographyappropriate dosebasecombatdisorder preventiondrug efficacydrug testingefficacy testingfluorodeoxyglucoseimprovedmathematical analysismathematical modelmortalitynovel drug combinationpre-clinicalprogramsresistant strainserial imagingside effecttransmission process
项目摘要
Abstract
Tuberculosis remains a major threat worldwide, with significant morbidity and mortality. Although drug
treatment is available, the regimen is lengthy with drugs that can have toxicity. The emergence of drug
resistant strains of Mycobacterium tuberculosis leads to treatment with suboptimal second line therapy. New
strategies are necessary for effectively combating tuberculosis.
This project is the culmination of the other projects and cores in the Program Project, in that drug regimens
identified and tested in smaller animal models and optimized by mathematical modeling will be tested for
efficacy in a large animal model. The cynomolgus macaque model is arguably the closest to humans in terms
of M. tuberculosis infection outcome, pathology and disease presentation. Our previous work demonstrated the
utility of this model in testing drugs against tuberculosis, with similar outcomes in humans and macaques. We
combine detailed necropsy and bacterial burden determinations with advanced serial imaging using Positron
Emission Tomography and Computed Tomography (PET/CT) to identify successful regimens. Here we will
compare two combinations identified, tested and optimized in the other projects and cores, for efficacy against
TB in macaques. These combination regimens will be compared separately and sequentially, providing
preclinical data that can be used to choose the best regimen to take into human clinical trials.
摘要
结核病仍然是全世界的一个主要威胁,发病率和死亡率都很高。尽管药物
治疗是可用的,该方案是漫长的药物,可以有毒性。药物的出现
结核分枝杆菌的耐药菌株导致用次优的二线疗法进行治疗。新
有效防治结核病的战略是必要的。
该项目是其他项目的高潮,也是该项目的核心,
在较小的动物模型中鉴定和测试,并通过数学建模进行优化,
在大型动物模型中的功效。食蟹猴模型可以说是最接近人类的术语
分枝结核感染结果、病理和疾病表现。我们以前的工作表明,
该模型在测试抗结核药物中的实用性,在人类和猕猴中具有相似的结果。我们
联合收割机将详细的尸检和细菌负荷测定与使用Positron的先进系列成像相结合
发射断层扫描和计算机断层扫描(PET/CT),以确定成功的方案。这里我们将
比较在其他项目和核心中确定、测试和优化的两种组合,
猕猴的结核病。这些联合治疗方案将分别和顺序进行比较,
临床前数据可用于选择最佳方案进行人体临床试验。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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JoAnne L. Flynn其他文献
This information is current as Infection Mycobacterium tuberculosis during Antimicrobial Responses with Caseation Mediated − Early Host Immunity Control of Lesion Sterilization by Balancing Computational Modeling Predicts IL-10
此信息是当前的感染结核分枝杆菌在干酪介导的抗菌反应期间通过平衡计算模型预测 IL-10 进行病灶灭菌的早期宿主免疫控制
- DOI:
- 发表时间:
2014 - 期刊:
- 影响因子:0
- 作者:
Nicholas A. Cilfone;Christopher B Ford;Simeone Marino;Joshua T Mattila;H. Gideon;JoAnne L. Flynn;Denise E. Kirschner;J. Linderman - 通讯作者:
J. Linderman
Modeling pathogen and host: <em>in vitro</em>, <em>in vivo</em> and <em>in silico</em> models of latent <em>Mycobacterium tuberculosis</em> infection
- DOI:
10.1016/j.ddmod.2005.05.019 - 发表时间:
2005-06-01 - 期刊:
- 影响因子:
- 作者:
P. Ling Lin;Denise Kirschner;JoAnne L. Flynn - 通讯作者:
JoAnne L. Flynn
emIn silico/em identification and synthesis of a multi-drug loaded MOF for treating tuberculosis
- DOI:
10.1016/j.jconrel.2022.10.024 - 发表时间:
2022-12-01 - 期刊:
- 影响因子:11.500
- 作者:
Abhinav P. Acharya;Kutay B. Sezginel;Hannah P. Gideon;Ashlee C. Greene;Harrison D. Lawson;Sahil Inamdar;Ying Tang;Amy J. Fraser;Kush V. Patel;Chong Liu;Nathaniel L. Rosi;Stephen Y. Chan;JoAnne L. Flynn;Christopher E. Wilmer;Steven R. Little - 通讯作者:
Steven R. Little
This information is current as Infection in BALB / c Mice tuberculosis Mycobacterium the Control of Chronic The Chemokine Receptor CXCR 3 Attenuates
此信息当前为 BALB / c 小鼠结核分枝杆菌感染控制慢性趋化因子受体 CXCR 3 减弱
- DOI:
- 发表时间:
2007 - 期刊:
- 影响因子:0
- 作者:
S. Chakravarty;Jiayong Xu;Bao Lu;Craig Gerard;JoAnne L. Flynn;John Chan - 通讯作者:
John Chan
SARS-CoV-2 Receptor ACE2 is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Enriched in Specific Cell Subsets Across Tissues
SARS-CoV-2 受体 ACE2 是人气道上皮细胞中的干扰素刺激基因,富含组织中的特定细胞亚群
- DOI:
- 发表时间:
2020 - 期刊:
- 影响因子:0
- 作者:
Carly N Ziegler;Samuel J. Allon;Sarah K Nyquist;Ian M. Mbano;Vincent N Miao;Yuming Cao;Ashraf S. Yousif;Julia Bals;B. Hauser;J. Feldman;Christoph Muus;Marc H Wadsworth Ii;S. Kazer;T. Hughes;B. Doran;G. J. Gatter;Marko Vukovic;C. Tzouanas;F. Taliaferro;Zhiru Guo;Jennifer P. Wang;Daniel F Dwyer;K. Buchheit;Joshua A. Boyce;Nora A. Barrett;T. Laidlaw;Shaina L. Carroll;Lucrezia Colonna;V. Tkachev;Alison Yu;Henqi Betty Zheng;H. Gideon;Caylin G. Winchell;P. Lin;Bonnie Berger;A. Leslie;JoAnne L. Flynn;Sarah M Fortune;R. Finberg;Leslie S. Kean;Manuel Garber;Aaron Schmidt;D. Lingwood;A. Shalek;J. Ordovas;Hca Lung Biological Network - 通讯作者:
Hca Lung Biological Network
JoAnne L. Flynn的其他文献
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{{ truncateString('JoAnne L. Flynn', 18)}}的其他基金
Enhancing cytotoxic lymphocytes in a TB vaccine strategy
在结核病疫苗策略中增强细胞毒性淋巴细胞
- 批准号:
10462928 - 财政年份:2022
- 资助金额:
$ 79.98万 - 项目类别:
Enhancing cytotoxic lymphocytes in a TB vaccine strategy
在结核病疫苗策略中增强细胞毒性淋巴细胞
- 批准号:
10580073 - 财政年份:2022
- 资助金额:
$ 79.98万 - 项目类别:
Dissecting the pathogenesis of HIV-TB Immune reconstitution inflammatory syndrome
剖析 HIV-TB 免疫重建炎症综合征的发病机制
- 批准号:
10097199 - 财政年份:2020
- 资助金额:
$ 79.98万 - 项目类别:
Dissecting the pathogenesis of HIV-TB Immune reconstitution inflammatory syndrome
剖析 HIV-TB 免疫重建炎症综合征的发病机制
- 批准号:
10451735 - 财政年份:2020
- 资助金额:
$ 79.98万 - 项目类别:
Dissecting the pathogenesis of HIV-TB Immune reconstitution inflammatory syndrome
剖析 HIV-TB 免疫重建炎症综合征的发病机制
- 批准号:
10667439 - 财政年份:2020
- 资助金额:
$ 79.98万 - 项目类别:
Dissecting the pathogenesis of HIV-TB Immune reconstitution inflammatory syndrome
剖析 HIV-TB 免疫重建炎症综合征的发病机制
- 批准号:
10240712 - 财政年份:2020
- 资助金额:
$ 79.98万 - 项目类别:
Predicting protective T-cell responses in Tuberculosis using a systems biology approach
使用系统生物学方法预测结核病中的保护性 T 细胞反应
- 批准号:
9072491 - 财政年份:2016
- 资助金额:
$ 79.98万 - 项目类别:
The Effects of M. tuberculosisInfection on Lung Microbiome in Macaques
结核分枝杆菌感染对猕猴肺部微生物组的影响
- 批准号:
9018134 - 财政年份:2016
- 资助金额:
$ 79.98万 - 项目类别:
An adjuvant that promotes TH1/TH17 and CD8 T cells in a tuberculosis vaccine
一种在结核疫苗中促进 TH1/TH17 和 CD8 T 细胞的佐剂
- 批准号:
8607041 - 财政年份:2013
- 资助金额:
$ 79.98万 - 项目类别:
An adjuvant that promotes TH1/TH17 and CD8 T cells in a tuberculosis vaccine
一种在结核疫苗中促进 TH1/TH17 和 CD8 T 细胞的佐剂
- 批准号:
8994259 - 财政年份:2013
- 资助金额:
$ 79.98万 - 项目类别:
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