Neurocognitive and neuroimaging markers of emerging cerebral adrenoleukodystrophy
新发脑性肾上腺脑白质营养不良的神经认知和神经影像学标志物
基本信息
- 批准号:10678672
- 负责人:
- 金额:$ 15.85万
- 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:2022-08-08 至 2027-06-30
- 项目状态:未结题
- 来源:
- 关键词:10 year oldAdrenal gland hypofunctionAdrenoleukodystrophyAdrenomyeloneuropathyAffectAppearanceAttentionBehavior assessmentBehavioralBirthBrainBrain DiseasesCerebrumCessation of lifeChildChildhoodClinicalClinical Research ProtocolsClinical TrialsClinical Trials DesignComputing MethodologiesCorpus CallosumDataDemyelinating DiseasesDemyelinationsDetectionDeteriorationDevelopmentDevelopment PlansDiagnosisDiffusion Magnetic Resonance ImagingDiseaseDisease MarkerDisease ProgressionEarly identificationEarly treatmentEncephalitisFiberFingersFundingFutureGoalsGuidelinesHematopoietic Stem Cell TransplantationIndividualInformal Social ControlInvestigationInvestigational TherapiesK-Series Research Career ProgramsKnowledgeLesionLinkMagnetic Resonance ImagingMeasuresMentorshipMethodologyMethodsMinnesotaModalityMonitorMorbidity - disease rateMyelinNeonatal ScreeningNeurocognitiveNeurocognitive DeficitNeurodegenerative DisordersNeurodevelopmental DisorderOnset of illnessOutcomePathogenicityPatient-Focused OutcomesPatientsProtocols documentationPublic HealthRecommendationResearchResearch DesignResearch PersonnelRiskStatistical MethodsTestingTrainingTreatment EfficacyUniversitiesValidationVariantWorkattentional controlboysbrain dysfunctionbrain magnetic resonance imagingcareercareer developmentcomputerizeddesigneffective interventionexperiencehuman old age (65+)improvedimproved outcomeinterhemispheric transfermalemortalitynerve injurynervous system disorderneurocognitive testneuroimagingneuroimaging markernovelnovel therapeuticspre-clinicalpreventprogramsresearch and developmentresearch studyscreening programstatistical learningstem cell therapytooltranslational scientistwhite matter
项目摘要
Project Summary/Abstract
Adrenoleukodystrophy (ALD) is a progressive X-linked neurological disorder with unpredictable variation in
expression. During childhood, about 1 in 3 boys develop rapidly progressing cerebral ALD with brain
inflammation and myelin destruction. Although existing treatments stop progression of cerebral ALD when
detected at an early stage, no current assessments can identify which boys will develop cerebral ALD or when
it will begin. Newborn screening programs that identify ALD at birth offer an opportunity to provide earlier
treatment that avoids irreversible neurocognitive decline while new treatments may present safer alternatives
to standard stem cell therapy. This K23 Career Development Award aims to provide the PI with the necessary
training to become an independent investigator proficient in cross-modal methodologies to measure subtle
brain changes in children with ALD and apply those methods in clinical research protocols. With mentorship
from a team of experts at the University of Minnesota, the applicant proposes the following training objectives:
(1) to obtain knowledge and experience in acquisition and analysis of neuroimaging data; (2) to learn statistical
and computational methods for validation of novel neurocognitive tests; and (3) to acquire the expertise to
design and execute clinical trials. The overall research objectives are designed to identify early neurocognitive
and neuroimaging markers of cerebral demyelination and enhance the capacity of clinical trials of newer
therapies to define robust endpoints for boys who receive early treatment. The central hypothesis is that
deterioration in white matter fiber integrity and associated loss of interhemispheric function involving the corpus
callosum mark the onset of cerebral ALD, and begin prior to the appearance of a lesion on MRI. To test this
hypothesis, the PI will test several methods designed to measure changes associated with demyelination. The
specific aims will use longitudinal neurocognitive testing (Aim 1) and longitudinal diffusion MRI studies (Aim 2)
to identify functional and microstructural markers of cerebral ALD in boys with early stage disease, and test for
presence of these markers during the critical pre-emergent stage in at-risk boys. The neurocognitive findings
will also be compared to MRI metrics of disease progression. The successful completion of these Aims will
identify reliable indicators of disease onset and early progression. The proposed research is significant
because detection and quantification of subtle progressive brain changes in boys with ALD will allow earlier
and more effective intervention to reduce the neurocognitive morbidity. The training objectives will support the
applicant's career goals to lead a long-term program of research to identify sensitive markers of brain
dysfunction in neurodevelopmental and neurodegenerative diseases, with the goal of informing timing and
efficacy of interventions to achieve better patient outcomes.
项目总结/文摘
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
A dimensional approach to neurodevelopmental differences in genetically well-defined populations: What's next?
基因明确人群神经发育差异的维度方法:下一步是什么?
- DOI:10.1111/dmcn.15634
- 发表时间:2023
- 期刊:
- 影响因子:3.8
- 作者:Pierpont,ElizabethI
- 通讯作者:Pierpont,ElizabethI
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Elizabeth Irene Pierpont其他文献
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{{ truncateString('Elizabeth Irene Pierpont', 18)}}的其他基金
Neurocognitive and neuroimaging markers of emerging cerebral adrenoleukodystrophy
新发脑性肾上腺脑白质营养不良的神经认知和神经影像学标志物
- 批准号:
10524184 - 财政年份:2022
- 资助金额:
$ 15.85万 - 项目类别:














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