Measurement of ART Drug Concentrations in Brain by 19F-MRS as an Indicator of Neurotoxicity
通过 19F-MRS 测量脑内 ART 药物浓度作为神经毒性指标
基本信息
- 批准号:9925549
- 负责人:
- 金额:$ 19.69万
- 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:2019-09-24 至 2021-07-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdverse eventAgingAnimalsBiological AgingBiological AssayBiomedical ResearchBloodBlood - brain barrier anatomyBrainCD4 Positive T LymphocytesCerebrospinal FluidCerebrumCognition DisordersCommunitiesComplexDataDetectionDevelopmentDiseaseDoseEtiologyExploratory/Developmental GrantFluorineFluoxetineFluvoxamineFutureGeneral PopulationGiftsHIVHIV antiretroviralHeadHealthHumanIn VitroInflammationInjuryIntegrase InhibitorsInvestigationInvestmentsLeadMagnetic Resonance SpectroscopyMeasurementMeasuresMethodsMitochondriaMood DisordersMoodsN-acetylaspartateNational Institute of Mental HealthNational NeuroAids Tissue ConsortiumNeuraxisNeurobehavioral ManifestationsNeurocognitiveNeuronal InjuryNeuropharmacologyParticipantPerformancePermeabilityPersonsPharmaceutical PreparationsPharmacologyPrevalenceProtonsPublicationsPublishingRNARecoveryReportingResearchResearch Project GrantsRiskRisk FactorsSafetySample SizeSelective Serotonin Reuptake InhibitorSeveritiesSignal TransductionSleepSymptomsTissuesUnited States National Institutes of HealthViralWorkantiretroviral therapybrain researchbrain tissuecohortdaily functioningefavirenzemtricitabinefallsimprovedin vivoinnovationlow and middle-income countrieslymph nodesneurobehavioralneuropsychiatryneurotoxicitynew technologyprogramspublic health relevanceradioligandside effecttool
项目摘要
ABSTRACT
Antiretroviral therapy (ART) can suppress HIV RNA and improve survival but concerns about the
neurotoxicity of ART drugs have arisen in recent years with the publication of reports of a) in vitro evidence of
neuronal injury and b) neuropsychiatric adverse events (NP-AEs) of efavirenz, dolutegravir (DTG), and other
drugs. A key gap in our understanding of the efficacy and safety of ART drugs in the CNS is the pharmacology
of these drugs in the brain. Published human studies have reported that concentrations of most ART drugs are
substantially lower in cerebrospinal fluid (CSF) than in blood but recent animal studies have reported that ART
drug concentrations in the brain are substantially higher than expected by on CSF data. High ART drug
concentrations in the brain could be a critical determinant of neurotoxicity risk. To better understand the influence
of ART drug concentrations on NP-AEs, a new method is needed to measure these concentrations in the brain
of living humans. This R21 application proposes highly innovative research to develop such a method, fluorine
magnetic resonance spectroscopy (19F-MRS). This method can measure low concentration compounds, like
fluorinated drugs, that fall within the 19F-MRS spectra in vivo. This could be highly valuable since many commonly
used ART drugs, such as DTG and emtricitabine (FTC), are fluorinated. This method does not require
administration of a radioligand and has successfully measured concentrations of fluorinated selective serotonin
reuptake inhibitors in the past. The proposed research responds well to RFA-MH-20-115 and is organized into
3 aims: 1) Develop the 19F-MRS method to measure concentrations of DTG and FTC in the brain, 2) Measure
DTG and FTC by 19F-MRS in 20 participants of the CHARTER Aging project (R01 MH107345), which will
leverage NIMH’s investment in this cohort, and 3) Determine the relationships between DTG and FTC
concentrations in brain tissue and assessments of neurocognitive performance, mood, sleep, and daily
functioning, which are being performed by the CHARTER Aging project. While the proposed sample size is small,
the findings will provide proof-of-principle and preliminary data in support of future projects. The successful
project will develop a new and highly impactful tool for research on ART neuropharmacology and neurotoxicity
and will lead to new, larger research projects. It may also be useful in development of new ART drugs. This
method can also be used to measure ART drugs concentrations in tissues other than brain (e.g., lymph nodes)
so its development could also lead to new research on HIV persistence and eradication.
文摘
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)
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Scott L Letendre其他文献
Neurocognitive effects of HCV, methamphetamine abuse, and HIV: multiple risks and mechanisms
- DOI:
10.1186/1744-859x-7-s1-s39 - 发表时间:
2008-04-17 - 期刊:
- 影响因子:3.100
- 作者:
Scott L Letendre - 通讯作者:
Scott L Letendre
Scott L Letendre的其他文献
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{{ truncateString('Scott L Letendre', 18)}}的其他基金
Aging, Polypharmacy and Neurotoxicity in Adults Living with HIV
成人艾滋病毒感染者的衰老、多药治疗和神经毒性
- 批准号:
10577736 - 财政年份:2020
- 资助金额:
$ 19.69万 - 项目类别:
Aging, Polypharmacy and Neurotoxicity in Adults Living with HIV
成人艾滋病毒感染者的衰老、多药治疗和神经毒性
- 批准号:
10374038 - 财政年份:2020
- 资助金额:
$ 19.69万 - 项目类别:
Aging, Polypharmacy and Neurotoxicity in Adults Living with HIV
成人艾滋病毒感染者的衰老、多药治疗和神经毒性
- 批准号:
10013739 - 财政年份:2020
- 资助金额:
$ 19.69万 - 项目类别:
Measurement of ART Drug Concentrations in Brain by 19F-MRS as an Indicator of Neurotoxicity
通过 19F-MRS 测量脑内 ART 药物浓度作为神经毒性指标
- 批准号:
10023281 - 财政年份:2019
- 资助金额:
$ 19.69万 - 项目类别:
Sustained Training in Aging and HIV Research (STAHR)
老龄化和艾滋病毒研究持续培训(STAHR)
- 批准号:
10483564 - 财政年份:2016
- 资助金额:
$ 19.69万 - 项目类别:
Sustained Training in Aging and HIV Research (STAHR)
老龄化和艾滋病毒研究持续培训(STAHR)
- 批准号:
10615240 - 财政年份:2016
- 资助金额:
$ 19.69万 - 项目类别:
Midcareer Investigator Award in Patient-Oriented NeuroAIDS Research
以患者为导向的神经艾滋病研究中职业生涯调查员奖
- 批准号:
8466639 - 财政年份:2012
- 资助金额:
$ 19.69万 - 项目类别:
Midcareer Investigator Award in Patient-Oriented NeuroAIDS Research
以患者为导向的神经艾滋病研究中职业生涯调查员奖
- 批准号:
8774931 - 财政年份:2012
- 资助金额:
$ 19.69万 - 项目类别:
Midcareer Investigator Award in Patient-Oriented NeuroAIDS Research
以患者为导向的神经艾滋病研究中职业生涯调查员奖
- 批准号:
8594262 - 财政年份:2012
- 资助金额:
$ 19.69万 - 项目类别:
Midcareer Investigator Award in Patient-Oriented NeuroAIDS Research
以患者为导向的神经艾滋病研究中职业生涯调查员奖
- 批准号:
8968863 - 财政年份:2012
- 资助金额:
$ 19.69万 - 项目类别:
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