Development of Synthetic High-Density Lipoproteins for Treatment of Sepsis
用于治疗脓毒症的合成高密度脂蛋白的开发
基本信息
- 批准号:10569516
- 负责人:
- 金额:$ 64.38万
- 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:2022-02-15 至 2024-10-31
- 项目状态:已结题
- 来源:
- 关键词:AnimalsAnti-Inflammatory AgentsAntibioticsApolipoprotein A-IBacterial InfectionsBloodCardiovascular DiseasesCardiovascular systemClinicalClinical ChemistryClinical DataClinical ProtocolsClinical ResearchCoagulation ProcessCommunicable DiseasesComplexContractsCustomDevelopmentDoseDropsEndotoxinsEnsureEquilibriumEvaluationFeedbackGenerationsGrantHealthHealth Care CostsHigh Density LipoproteinsHumanHypotensionIL8 geneImmune responseIndustrializationIndustryInflammationInflammatoryInfusion proceduresInterleukin-6IntravenousInvestigational DrugsInvestigational New Drug ApplicationLaboratoriesLigationMaximum Tolerated DoseMethodologyMethodsMichiganMusOrganOrgan failurePathologyPathway interactionsPatient CarePatient-Focused OutcomesPatientsPeptide SynthesisPharmaceutical PreparationsPharmacologic SubstancePhasePhosphorylcholinePlayPreventionProcessProductionPrognosisPropertyRattusRecommendationResearchRodentRoleSafetySepsisSeptic ShockSeveritiesSterilitySymptomsSystemTNF geneTechnology TransferTestingTextTherapeuticThrombosisToxic effectToxicokineticsToxicologyUnited StatesUniversitiesVascular Endothelial CellVeteransanalytical methodclinical developmentclinical translationcytokinedrug candidateeffective therapyefficacy outcomesimmunoreactionimprovedmanufacturemanufacturing organizationmanufacturing processmeetingsmortalitymouse modelmultidisciplinarynovel therapeuticsparticlepeptide Ipharmacokinetics and pharmacodynamicspre-Investigational New Drug meetingpre-clinicalpreclinical developmentpreclinical studypredictive markerproduct developmentprognostic of survivalprophylacticresearch clinical testingresponse biomarkerscale upsepticseptic patients
项目摘要
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Sepsis represents a major health issue, which claims over 270,000 lives each year in the United States alone, resulting in more than $23 billion in health care costs. While sepsis is caused by bacterial infections that are treated with intravenous
(IV) antibiotics, the often very rapid progression into septic shock and ultimately organ failure is a consequence of an overreaction of the immune and coagulation system. The prognosis for sepsis remains poor, with mortality rates exceeding 30%, due to a lack of effective treatment options. Thus far, efforts to therapeutically block any single step in the inflammation or coagulation pathways have had little impact on patient survival. High-density lipoprotein (HDL) is a key component of circulating blood and plays essential roles in vascular endothelial cell (EC) health and balance of the immune system response. Clinical data demonstrate that HDL levels drop by 40-70% in septic patients, which is associated with poor survival prognosis. We and others have shown that infusions of synthetic HDL (sHDL) result in improved survival in mouse models of sepsis. Prophylactic administration of a first generation sHDL product in humans subsequently challenged with an endotoxin infusion was shown to suppress inflammation, inhibit hypotension and markedly decrease the severity of clinical symptoms. These preclinical and clinical studies indicate that replenishing circulating HDL in sepsis patients may provide an effective therapy approach, and HDL itself may serve as a predictive marker for patient outcomes.
Previous sHDL candidates have been tested clinically in sepsis relevant settings, but development was discontinued due to safety concerns related to product impurities. Newer and safer versions of sHDL have been developed which have been shown to be safe in humans. We have since developed SPS-701, with further optimized composition to maximize anti- inflammatory properties and utility for sepsis. The objective of this grant is therefore to perform the initial preclinical studies and develop the regulatory strategy for filing an Investigational New Drug (IND) application to advance SPS-701 towards clinical evaluation for the treatment of sepsis.
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项目成果
期刊论文数量(0)
专著数量(0)
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Elke Lipka其他文献
Elke Lipka的其他文献
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10546933 - 财政年份:2022
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$ 64.38万 - 项目类别:
Development of Synthetic High-Density Lipoproteins for Treatment of Sepsis
用于治疗脓毒症的合成高密度脂蛋白的开发
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10384700 - 财政年份:2022
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$ 64.38万 - 项目类别:
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9888308 - 财政年份:2019
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9436472 - 财政年份:2018
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10699105 - 财政年份:2017
- 资助金额:
$ 64.38万 - 项目类别:
Microneedle Delivery of Zanamivir for the Treatment of Influenza Infections
扎那米韦微针治疗流感感染
- 批准号:
10614045 - 财政年份:2017
- 资助金额:
$ 64.38万 - 项目类别:
Microneedle Delivery of Zanamivir for Treatment of Influenza Infections
扎那米韦微针治疗流感感染
- 批准号:
9438857 - 财政年份:2017
- 资助金额:
$ 64.38万 - 项目类别:
Microneedle Delivery of Zanamivir for Treatment of Influenza
扎那米韦微针治疗流感
- 批准号:
10132966 - 财政年份:2017
- 资助金额:
$ 64.38万 - 项目类别:
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