TARGETING HIF-1α DYSFUNCTION TO TREAT PRESSURE ULCERS IN THE AGED
针对 HIF-1α 功能障碍治疗老年人压疮
基本信息
- 批准号:10444745
- 负责人:
- 金额:$ 32.57万
- 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:2022-09-01 至 2027-05-31
- 项目状态:未结题
- 来源:
- 关键词:5 year oldAffectAge-YearsAgingAmericanAnimal ModelAnimalsBackBiopsy SpecimenButtocksCellsConsultDataDefectDeferoxamineDermisDiabetes MellitusDrug Delivery SystemsDrug usageElderlyFDA approvedFamily suidaeFibroblastsFunctional disorderGene TargetingHealth Care CostsHealthcare SystemsHumanHypoxiaImpaired wound healingImpairmentIncidenceIndividualInterventionLeadModelingMolecularMusNursing HomesOperative Surgical ProceduresPathway interactionsPatientsPersonsPharmaceutical PreparationsPharmacologyPreventionProtein AnalysisProteinsResearchRiskSafetySamplingSignal TransductionSkinSkin AgingSkin TissueSpecialistStratum corneumSystemTestingTimeTissuesTransdermal substance administrationUlcerUnited StatesUnited States National Institutes of HealthVascular DiseasesWorkage relatedagedaging populationchronic woundcomorbiditydecubitus ulcerdrug efficacyeffectiveness validationefficacy testinghealinghydrophilicityhypoxia inducible factor 1improvedneovascularizationnovelnovel strategiesnovel therapeutic interventionnovel therapeuticsolder patientporcine modelpreclinical studypressurepreventsingle cell sequencingskin ulcerskin woundsmall moleculestandard of caretranscriptomicswoundwound healing
项目摘要
Project Summary
Pressure ulcers affect 2.5 million people in the United States and cost the healthcare system an estimated 11.6
billion dollars annually. A major percentage of affected individuals are over sixty-five years of age and this
number is growing rapidly in the United States. A greater incidence of immobility, vascular disease and diabetes
is commonly seen in aged populations and places them at an increased risk for developing pressure ulcers.
Thus, there is a pressing need to develop new therapies that will effectively treat pressure ulcers in the aged.
With prior NIA support, we have found that aging is characterized by the progressive loss of critical molecular
and cellular pathways responsible for normal wound healing, specifically hypoxia-inducible factor 1-alpha (HIF-
1α). We have also identified that these changes can be reversed using an FDA-approved small molecule drug,
deferoxamine (DFO). Building on our preliminary data, we will first define the aberrations of HIF-1α in healthy,
unwounded skin from young and aged patients (Specific Aim 1). We will then confirm the HIF-1α signaling
dysfunction in pressure ulcers using biopsy specimens from both young and aged patients. (Specific Aim 2). To
define the alterations in hypoxia signaling within the skin cells of young versus aged patients, we will subject the
collected tissue for protein analysis and single cell sequencing. We will then determine the optimal delivery
system for DFO through both intact stratum corneum as required for treating pressure ulcers in a porcine model
(Specific Aim 3). This large animal model is selected since porcine skin has significant similarities to the human
skin. Our results will validate the effectiveness of our drug delivery system and provide a novel strategy to deliver
other hydrophilic small molecule drugs across intact human skin. Taken together, this pre-clinical study will lay
the groundwork for a pilot human trial targeted at treating pressure ulcers with the transdermal DFO delivery
system, which will for the first time provide a pharmacologic therapy to treat pressure ulcers in aged patients.
项目总结
项目成果
期刊论文数量(0)
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科研奖励数量(0)
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GEOFFREY C GURTNER其他文献
GEOFFREY C GURTNER的其他文献
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{{ truncateString('GEOFFREY C GURTNER', 18)}}的其他基金
TARGETING HIF-1α DYSFUNCTION TO TREAT PRESSURE ULCERS IN THE AGED
针对 HIF-1α 功能障碍治疗老年人压疮
- 批准号:
10685482 - 财政年份:2022
- 资助金额:
$ 32.57万 - 项目类别:
Diabetic Foot Ulcer Biofilm Infection and Recurrence
糖尿病足溃疡生物膜感染和复发
- 批准号:
10947670 - 财政年份:2020
- 资助金额:
$ 32.57万 - 项目类别:
Diabetic Foot Ulcer Biofilm Infection and Recurrence
糖尿病足溃疡生物膜感染和复发
- 批准号:
10417228 - 财政年份:2020
- 资助金额:
$ 32.57万 - 项目类别:
Diabetic Foot Ulcer Biofilm Infection and Recurrence
糖尿病足溃疡生物膜感染和复发
- 批准号:
10256045 - 财政年份:2020
- 资助金额:
$ 32.57万 - 项目类别:
Diabetic Foot Ulcer Biofilm Infection and Recurrence
糖尿病足溃疡生物膜感染和复发
- 批准号:
10044343 - 财政年份:2020
- 资助金额:
$ 32.57万 - 项目类别:
Diabetic Foot Ulcer Biofilm Infection and Recurrence
糖尿病足溃疡生物膜感染和复发
- 批准号:
10376509 - 财政年份:2020
- 资助金额:
$ 32.57万 - 项目类别:
Stanford Advanced Wound Care Center Clinical Research Unit
斯坦福高级伤口护理中心临床研究部
- 批准号:
10203948 - 财政年份:2018
- 资助金额:
$ 32.57万 - 项目类别:
Stanford Advanced Wound Care Center Clinical Research Unit
斯坦福高级伤口护理中心临床研究部
- 批准号:
10230438 - 财政年份:2018
- 资助金额:
$ 32.57万 - 项目类别:
Stanford Advanced Wound Care Center Clinical Research Unit
斯坦福高级伤口护理中心临床研究部
- 批准号:
10377776 - 财政年份:2018
- 资助金额:
$ 32.57万 - 项目类别:
The University of Arizona Wound Care Center Clinical Research Unit
亚利桑那大学伤口护理中心临床研究单位
- 批准号:
10877642 - 财政年份:2018
- 资助金额:
$ 32.57万 - 项目类别:
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