Directing Tryptophan Immunometabolism to Ameliorate Liver Ischemic-Reperfusion Injury
指导色氨酸免疫代谢改善肝脏缺血再灌注损伤
基本信息
- 批准号:10595020
- 负责人:
- 金额:$ 65.42万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-04-01 至 2025-12-31
- 项目状态:未结题
- 来源:
- 关键词:AcuteAddressAnti-Inflammatory AgentsAntibodiesAntigensAutomobile DrivingBiologicalBlood CirculationBlood flowCatalogsCell DeathCell physiologyCellsChronicCirculationClinicalCoupledDataDiseaseDoseDrug KineticsEngraftmentEnzymesEssential Amino AcidsFormulationFutureGoalsHalf-LifeHomeostasisImmuneImmune responseImmunocompromised HostImmunophenotypingImmunosuppressionIn VitroIncidenceInflammationInflammatoryInjectableInjectionsInjuryIschemiaKynurenineLeftLiquid substanceLiverLiver DysfunctionLiver FailureMaximum Tolerated DoseMediatorMetabolicMetabolismMyocardial InfarctionOperative Surgical ProceduresOrganOrgan failureOutcomePathologyPathway interactionsPharmaceutical PreparationsPharmacodynamicsPolyethylene GlycolsPositioning AttributeProcessReperfusion InjurySiteSterilityStrokeTechnologyTherapeuticTissuesToxic effectToxicologyTransplantationTraumaTryptophanTryptophan 2,3 DioxygenaseTryptophan Metabolism PathwayVascular blood supplycell injurycell typeclinical practicecytotoxicitydrug actiondruggable targetextracellularimmunogenicityimmunoregulationimplantationin vivoinnovationinterestintravenous administrationliver ischemianovel therapeutic interventionnovel therapeuticspreconditioningpreservationprogramsprophylacticrestorationside effectsuccesssystemic toxicitytissue repair
项目摘要
Project Summary/Abstract
Many different disease states and surgical interventions result in a period of inadequate
tissue/organ blood supply (i.e., ischemia), that result in reperfusion injury when blood flow is
restored, known as ischemia-reperfusion injury (IRI). IRI causes local inflammation, cell death,
excessive tissue destruction and possible organ failure. Examples are found in transplantation,
trauma, myocardial infarction, stroke, and in particular, IRI is a main cause of liver dysfunction
and failure after liver surgery. Unfortunately, there are currently no therapies available in clinical
practice addressing IRI, where a major problem is the harmful systemic side effects and toxicities
of existing drugs.
To address this problem, we are innovating a new therapeutic technology aiming to program
immune cells toward a metabolic state blocking excessive inflammation by directing tryptophan
metabolism through delivery of an enzyme into circulation. This represents a new class of anti-
inflammatory/immunosuppressive biologic drug, with potential to limit systemic toxicities/side
effects, and with potential to be significantly less immunocompromising. Lack of treatment options
for liver IRI and a catalog of in vivo preliminary data strongly supporting the foundational rationale
of IDO as an innovative new anti-inflammatory agent, make this proposal highly significant.
Looking to the future, success would open opportunity to expand to other anti-inflammatory
applications, for example, pre-conditioning donor grafts for transplantation.
项目总结/摘要
许多不同的疾病状态和手术干预导致一段时间的不充分
组织/器官血液供应(即,缺血),当血流被阻断时,
恢复,称为缺血再灌注损伤(IRI)。IRI导致局部炎症细胞死亡,
过度的组织破坏和可能的器官衰竭例如在移植中,
创伤、心肌梗塞、中风,特别是IRI是肝功能障碍的主要原因
以及肝脏手术后的衰竭不幸的是,目前临床上没有可用的治疗方法。
处理IRI的实践,其中一个主要问题是有害的全身副作用和毒性
现有的药物。
为了解决这个问题,我们正在创新一种新的治疗技术,
通过引导色氨酸,免疫细胞进入代谢状态,
通过将酶输送到循环中进行新陈代谢。这代表了一种新的反-
炎症/免疫抑制生物药物,可能限制全身毒性/副作用
效果,并且具有显著降低免疫妥协的潜力。缺乏治疗选择
对于肝脏IRI和一个强烈支持基本原理的体内初步数据目录
IDO作为一种创新的新型抗炎剂,使这一建议非常重要。
展望未来,成功将打开机会,扩大到其他抗炎药
例如,预处理供体移植物用于移植。
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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Benjamin George Keselowsky其他文献
Benjamin George Keselowsky的其他文献
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{{ truncateString('Benjamin George Keselowsky', 18)}}的其他基金
Directing Tryptophan Immunometabolism to Ameliorate Liver Ischemic-Reperfusion Injury
指导色氨酸免疫代谢改善肝脏缺血再灌注损伤
- 批准号:
10444213 - 财政年份:2022
- 资助金额:
$ 65.42万 - 项目类别:
Diversity Supplement: Directing Tryptophan Immunometabolism to Ameliorate Liver Ischemic-Reperfusion Injury
多样性补充剂:引导色氨酸免疫代谢改善肝脏缺血再灌注损伤
- 批准号:
10632561 - 财政年份:2022
- 资助金额:
$ 65.42万 - 项目类别:
Functionalized Enzyme Treatments for Dual-Targeting of Inflammation in Spinal Cord Injury
功能化酶治疗脊髓损伤炎症的双重靶向
- 批准号:
10284992 - 财政年份:2021
- 资助金额:
$ 65.42万 - 项目类别:
Tissue-Targeted Enzyme for Localized Tryptophan Catabolism to Direct Subcutaneous and Oral Mucosal Inflammatory Responses
用于局部色氨酸分解代谢的组织靶向酶以指导皮下和口腔粘膜炎症反应
- 批准号:
9752509 - 财政年份:2017
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Tissue-Targeted Enzyme for Localized Tryptophan Catabolism to Direct Subcutaneous and Oral Mucosal Inflammatory Responses
用于局部色氨酸分解代谢的组织靶向酶以指导皮下和口腔粘膜炎症反应
- 批准号:
9403768 - 财政年份:2017
- 资助金额:
$ 65.42万 - 项目类别:
Biomaterial Delivery System for Type 1 Diabetes Vaccine
1 型糖尿病疫苗的生物材料输送系统
- 批准号:
9285796 - 财政年份:2014
- 资助金额:
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Biomaterial Delivery System for Type 1 Diabetes Vaccine
1 型糖尿病疫苗的生物材料输送系统
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8761784 - 财政年份:2014
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Dendritic Cell-Targeting Microparticles for Subcellularly-Targeted Delivery of In
用于亚细胞靶向递送 In 的树突状细胞靶向微粒
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8707719 - 财政年份:2012
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$ 65.42万 - 项目类别:
Dendritic Cell-Targeting Microparticles for Subcellularly-Targeted Delivery of In
用于亚细胞靶向递送 In 的树突状细胞靶向微粒
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9041572 - 财政年份:2012
- 资助金额:
$ 65.42万 - 项目类别:
Dendritic Cell-Targeting Microparticles for Subcellularly-Targeted Delivery of In
用于亚细胞靶向递送 In 的树突状细胞靶向微粒
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8442857 - 财政年份:2012
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