Infant NeuroLUX: A Novel Non-invasive Therapeutic Device for Neonatal Hypoxic Brain Injury
Infant NeuroLUX:一种治疗新生儿缺氧性脑损伤的新型非侵入性治疗装置
基本信息
- 批准号:10017347
- 负责人:
- 金额:$ 76.9万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-09-15 至 2022-08-31
- 项目状态:已结题
- 来源:
- 关键词:AchievementAddressAffectAnimal ModelAnimalsAreaAsphyxia NeonatorumAttenuatedBackBasic ScienceBirthBlood flowBrainBrain DiseasesBrain HypoxiaBrain Hypoxia-IschemiaBrain InjuriesBrain IschemiaCerebral PalsyCerebrumChildClinicalClinical TreatmentCombined Modality TherapyContractsDataDevelopmentDevelopmental Delay DisordersDevicesDocumentationDoseEngineeringEnsureEpilepsyEventExposure toFamily suidaeFree RadicalsGenerationsGoalsGoldHealthHistologicHospitalsHourHypoxiaHypoxic Brain DamageHypoxic-Ischemic Brain InjuryImpaired cognitionIncidenceInfantInfant MortalityInfectionInjuryInterventionInvestigationLaboratoriesLightLogisticsManufacturer NameMediatingMethodsMitochondriaModelingMolecularMorbidity - disease rateNeonatalNervous System PhysiologyNervous System TraumaNeurocognitive DeficitNeurologicNeurological outcomeNewborn InfantOxidasesOxygenPathologicPenetrationPerinatalPhasePhototherapyPre-Clinical ModelPreclinical TestingProductionReactive Oxygen SpeciesReperfusion InjuryReperfusion TherapyResearchResourcesRespirationResuscitationSafetyScalp structureSurvivorsTechnologyTerm BirthTestingTherapeuticTimeTissuesTranslatingbasebrain tissuecytochrome C oxidase subunit IIcytochrome c oxidasecytotoxicdeprivationdesign and constructiondisabilityearly childhoodengineering designhypoxia neonatorumimprovedin uteroin vivoin vivo evaluationinnovationintrapartummultidisciplinarynatural hypothermianeonatal brainneonatal hypoxic-ischemic brain injuryneonateneurobehavioralneuromuscularneuroprotectionnovelprematurepreterm newbornpreventprototyperesponserestorationstandard carestandard of caresuccesstherapy development
项目摘要
Neonatal hypoxia/ischemia is a known cause of cerebral damage resulting from inadequate blood flow and/or
oxygen delivery to the infant brain before, during, or after birth. The occurrence among hospital deliveries is
~2-4 per 1000 full-term births with a drastic increase among premature newborns. The deficit in oxygen
delivery to the brain results in extensive damage and severe disabilities. Restoration of blood flow critical for
salvage of ischemic tissue, however, also causes significant cerebral damage due in part to cytotoxic reactive
oxygen species (ROS) generated upon reintroduction of oxygen. The current standard treatment for neonatal
hypoxia/ischemia is therapeutic hypothermia applied on average 4-6 hours after restoration of blood
flow/oxygen delivery. A safe and effective neuroprotective intervention that specifically targets reperfusion
injury during the early phase of reoxygenation would fill a critical unmet need in the treatment of infants
exposed to hypoxia/ischemia.
Our molecular studies on mitochondrial function uncovered a novel method to prevent ROS generation during
early reoxygenation. Indeed, our studies have, for the first time: (i) identified two wavelengths of infrared light
(IRL) that specifically and reversibly reduce mitochondrial respiration by acting on cytochrome c oxidase; and
(ii) documented that IRL, applied at the time of reoxygenation, is neuroprotective and limits ROS generation.
Based on these data, we propose develop iNeuroLUX, a device that will safely deliver therapeutic IRL to the
infant brain. To achieve this goal, Phase I will propose 2 experimental aims:
• Conduct ex vivo molecular investigation to define the safe therapeutic IRL dose that can be applied in our
large animal studies (Aim 1).
• Establish the effect of IRL on HIE in a large animal model of neonatal hypoxia/ischemia (Aim 2). We will
determine the effects of IRL on neurologic damage in a neonate swine model of hypoxia/ischemia and
investigate safety of IRL in undamaged tissues.
Phase II will build upon the findings in the first phase and:
• Design and construct a iNeuroLUX light-delivery prototype for testing IRL therapy (Aim 3).
• Establish the efficacy of iNeuroLUX and evaluate the concept of iNeuroLUX combination therapy with
hypothermia (Aim 4).
• Document critical safety parameters of iNeuroLUX to move forward with FDA approval (Aim 5).
This proposal combines multi-disciplinary expertise, compelling preliminary data, and state-of-the-art resources
available to our research team to address a highly significant health problem.
新生儿缺氧/缺血是由于血流不足和/或
出生前,期间或之后,向婴儿大脑递送氧气。医院分娩中的发生是
〜2-4每1000个完整的出生,早产新生儿的大幅增加。氧气不足
传递到大脑会导致广泛的损害和严重的疾病。血流的恢复至关重要
但是,挽救缺血组织也会导致明显的脑损伤,部分原因是细胞毒性反应性
重新引入氧气后产生的氧(ROS)。新生儿的当前标准治疗
缺氧/缺血是血液恢复后4-6小时平均施用的治疗性低温
流量/氧递送。一种安全有效的神经保护干预措施,专门针对再灌注
在重氧的早期阶段受伤将满足婴儿治疗的关键需求
暴露于低氧/缺血。
我们对线粒体功能的分子研究发现了一种新的方法,以防止在
早期重氧。实际上,我们的研究第一次:(i)确定了两个红外光的波长
(IRL)通过作用于细胞色素C氧化酶来特别和可逆地减少线粒体呼吸;和
(ii)证明在重氧时应用的IRL是神经保护性的,并限制了ROS的产生。
基于这些数据,我们提出了开发Ineurolux,该设备将安全输送热IRL
婴儿大脑。为了实现这一目标,第一阶段将提出2个实验目标:
•进行离体分子投资来定义可以在我们的
大型动物研究(目标1)。
•在新生儿缺氧/缺血的大动物模型中建立IRL对HIE的影响(AIM 2)。我们将
确定IRL对低氧/缺血的新生猪模型和缺血模型中神经系统损伤的影响
研究IRL在未造成的组织中的安全性。
第二阶段将基于第一阶段的发现,并且:
•设计并构建了用于测试IRL治疗的Ineurolux轻型原型(AIM 3)。
•建立Ineurolux的效率,并评估Ineurolux联合疗法的概念
体温过低(目标4)。
•记录Ineurolux的关键安全参数,以通过FDA批准前进(AIM 5)。
该建议结合了多学科专业知识,引人入胜的初步数据和最先进的资源
我们的研究团队可以解决一个严重的健康问题。
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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MAIK HUETTEMANN其他文献
MAIK HUETTEMANN的其他文献
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{{ truncateString('MAIK HUETTEMANN', 18)}}的其他基金
Development and Testing of LUCID: A Therapeutic Device for Brain Injury Following Infant Cardiac Arrest
LUCID 的开发和测试:婴儿心脏骤停后脑损伤的治疗装置
- 批准号:
10515831 - 财政年份:2022
- 资助金额:
$ 76.9万 - 项目类别:
Development and Testing of LUCID: A Therapeutic Device for Brain Injury Following Infant Cardiac Arrest
LUCID 的开发和测试:婴儿心脏骤停后脑损伤的治疗装置
- 批准号:
10708811 - 财政年份:2022
- 资助金额:
$ 76.9万 - 项目类别:
Non-invasive mitochondrial modulation therapy for ischemic stroke
缺血性中风的非侵入性线粒体调节疗法
- 批准号:
10352458 - 财政年份:2021
- 资助金额:
$ 76.9万 - 项目类别:
Non-invasive mitochondrial modulation therapy for ischemic stroke
缺血性中风的非侵入性线粒体调节疗法
- 批准号:
10231915 - 财政年份:2021
- 资助金额:
$ 76.9万 - 项目类别:
Non-invasive mitochondrial modulation therapy for ischemic stroke
缺血性中风的非侵入性线粒体调节疗法
- 批准号:
10583532 - 财政年份:2021
- 资助金额:
$ 76.9万 - 项目类别:
Infant NeuroLUX: A Novel Non-invasive Therapeutic Device for Neonatal Hypoxic Brain Injury
Infant NeuroLUX:一种治疗新生儿缺氧性脑损伤的新型非侵入性治疗装置
- 批准号:
10001121 - 财政年份:2019
- 资助金额:
$ 76.9万 - 项目类别:
Control of Cell Respiration and Apoptosis by Phosphorylation of Cytochrome c
通过细胞色素 c 磷酸化控制细胞呼吸和凋亡
- 批准号:
9982332 - 财政年份:2017
- 资助金额:
$ 76.9万 - 项目类别:
Control of Cell Respiration and Apoptosis by Phosphorylation of Cytochrome c
通过细胞色素 c 磷酸化控制细胞呼吸和凋亡
- 批准号:
9236889 - 财政年份:2017
- 资助金额:
$ 76.9万 - 项目类别:
Limiting brain reperfusion injury by controlling mitochondrial function
通过控制线粒体功能限制脑再灌注损伤
- 批准号:
9149032 - 财政年份:2015
- 资助金额:
$ 76.9万 - 项目类别:
Regulation of Respiration and Apoptosis by Cytochrome c Phosphorylation.
细胞色素 c 磷酸化对呼吸和细胞凋亡的调节。
- 批准号:
8306157 - 财政年份:2010
- 资助金额:
$ 76.9万 - 项目类别:
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