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Host targeted immunotherapy for TB treatment

结核病治疗的宿主靶向免疫疗法

基本信息

批准号：
8487363
负责人：
Mercedes Gonzalez-Juarrero
金额：
$ 19.22万
依托单位：
COLORADO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-01 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8487363
关键词：
Adjuvant Animal Model Anti-Bacterial Agents Antitubercular Agents Attention Bacillus (bacterium)Bacteria Categories Chronic Containment Country Data Development Drug Targeting Environment Equilibrium Eukaryotic Cell Extreme drug resistant tuberculosis France Goals Health Immune Immune Targeting Immune response Immunologics Immunosuppression Immunosuppressive Agents Immunotherapeutic agent Immunotherapy Incidence Infection Interleukin-10 Intervention Laboratories Lung Mediating Multi-Drug Resistance Multidrug-Resistant Tuberculosis Mus Mycobacterium Infections Mycobacterium tuberculosis National Institute of Allergy and Infectious Disease Outcome Pathologic Pathology Pathway interactions Patients Phagocytes Pharmaceutical Preparations Pharmacotherapy Phase Population Production RNA Regulation Reporting Research Research Personnel Role Small Interfering RNA Staging Testing Therapeutic Therapeutic Agents Transcript Treatment Protocols Tuberculosis Vaccines Validation Wild Type Mouse alternative treatment arm bactericide base chemotherapy combat cytokine design drug clearance drug discovery effective therapy experience gene therapy global health improved in vivo innovation meetings non-compliance novel pathogen public health relevance research facility response therapeutic target treatment strategy tuberculosis treatment

项目摘要

DESCRIPTION (provided by applicant): Current TB chemotherapy is incapable of rapidly eliminating one hundred percent of the Mycobacterium tuberculosis bacilli. Although 99% of the bacteria are eliminated within three weeks of commencing treatment, a small population (~ 1%) of drug-tolerant bacilli requires an additional 6-8 months of multidrug treatment to be eliminated. This treatment regimen results in a dramatic improvement in patient health early on and many patients therefore fail to complete the full long-term treatment. This limitation has facilitated te continued emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis strains which have spread globally. The primary goal of this proposal is to more rapidly eradicate drug tolerant bacilli using immunotherapeutic approaches. We believe it is possible to enhance the host's own bactericidal response by using immunotherapy to combat pulmonary immunosuppression. Our preliminary studies indicate that delivery of small interfering RNA [siRNA] transcripts targeting the TGF¿1 cytokine reduces the pulmonary bacterial load of mice chronically infected with Mycobacterium tuberculosis. Moreover, this effect is enhanced in the absence of the IL-10 cytokine. Here we will test whether siRNA targeting of TGF¿1 and IL-10 can enhance clearance of drug tolerant bacilli and whether this approach is efficacious in chronic MDR-TB infections. The outcomes will be documented using comprehensive bacteriologic, immunologic, pathologic approaches now routine in our laboratory. We are uniquely equipped with state-of-the-art BSL-III research facilities and have assembled a team of highly experienced researchers with expertise in the fields of mycobacteria infection and RNA regulation in eukaryotic cells. Thus, this application uses innovative, cutting- edge research to develop anti-bacterial products directed against NIAID Category C Priority Pathogens.

描述（由申请人提供）：目前的结核病化疗不能快速消灭100%的结核分枝杆菌。虽然99%的细菌在开始治疗的三周内被消灭，但一小部分（约1%）耐药杆菌需要另外6-8个月的多药治疗才能被消灭。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Host Directed Therapy for Chronic Tuberculosis via Intrapulmonary Delivery of Aerosolized Peptide Inhibitors Targeting the IL-10-STAT3 Pathway.

DOI：
10.1038/s41598-018-35023-0
发表时间：
2018-11-09
期刊：
Scientific reports
影响因子：
4.6
作者：
Upadhyay R;Sanchez-Hidalgo A;Wilusz CJ;Lenaerts AJ;Arab J;Yeh J;Stefanisko K;Tarasova NI;Gonzalez-Juarrero M
通讯作者：
Gonzalez-Juarrero M