Imaging neurodegeneration in multiple sclerosis
Imaging neurodegeneration in multiple sclerosis
批准号:
10330016
负责人:
PETER A CALABRESI
金额:
$59.65万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2013
资助国家:
美国
项目状态:
已结题
起止时间:
2013-04-01 至 2024-01-31
关键词:
AddressAfrican AmericanAlgorithmsAtrophicBiologicalBiologyBrainBrain imagingC3 geneCaringCerebrumCharacteristicsClinicalClinical ManagementClinical assessmentsComplementComplexCustomData PoolingData SetDecision MakingDevelopmentDisabled PersonsDiseaseDisease OutcomeDisease ProgressionEnhancing LesionEthnic OriginFemaleGanglionic LayerGenesGeneticGenetic LoadGenetic Predisposition to DiseaseGenetic RiskGenetic VariationGenotypeGrantHealthImageIndividualInflammatoryInner Plexiform LayerLifeMagnetic Resonance ImagingMeasuresMethodologyMethodsModelingMonitorMultiple SclerosisNerve DegenerationNeuraxisNeurodegenerative DisordersNeuronsNeuroprotective AgentsOptical Coherence TomographyOutcomePathologyPathway interactionsPatient CarePatient Care ManagementPatientsPersonsPopulation CharacteristicsPredispositionQuality of lifeRaceResolutionRetinaRetinal DegenerationRetinal DiseasesRetinal Ganglion CellsRiskSeverity of illnessSiteStructureThalamic structureTherapeuticThickThinnessTimeToxic effectVariantVisualaggressive therapyaxonal degenerationburden of illnesscaucasian Americancentral nervous system demyelinating disorderclinical predictorscognitive functioncohortdisabilitydisability riskdisease prognosisefficacy testingfollow-upganglion cellgenetic analysisgenetic variantgray matterhigh resolution imaginghigh riskimaging geneticsimaging studyimprovedindividual patientinsightlarge datasetsmalemultiple sclerosis patientmultiple sclerosis treatmentnegative affectneuronal survivalnovelprecision medicineprediction algorithmpredictive modelingpredictive toolsrecruitresearch clinical testingretinal imagingrisk variantsextool
中文摘要
项目总结
英文摘要
Project Summary
One of the significant challenges facing treatment of people with multiple sclerosis (MS) is determining
their individual likelihood of progression, as this information would significantly influence the type of therapy
selected. Thus, developing specific tools to monitor and predict progression is critical to better manage patient
care and to understand mechanisms of disease. We have been developing a multi-faceted approach to more
readily monitor (through imaging) and predict (through both imaging and genetic analysis) disease progression
in a real-time fashion. In the past cycle of this grant we demonstrated the utility of high resolution spectral
domain optical coherence tomography (SD-OCT) and magnetic resonance imaging (3T MRI) in estimating
disease burden in different CNS compartments. We showed that retinal degeneration occurs throughout the
disease course and mirrors grey matter compartment atrophy in the cerebrum. A critical finding validating the
clinical utility of this approach was that in a multicenter analysis of pooled data, a single OCT at baseline
predicted risk of disability progression at 5 years of follow up. As MS is thought to have a strong genetic
component, we sought to investigate whether there was an underlying genetic predisposition towards
progression, which was made possible by the ability to utilize OCT in a real-time fashion to monitor
degeneration and correlate with clinical outcome. We thus expanded the imaging study to include a genetic
component in which we conducted a gene array to evaluate genetic variation among people with
heterogeneous courses of MS and have preliminarily found that several gene variants in network pathways
appear to be associated with more rapid rates of retinal neurodegeneration. The large data set that will be
generated from these studies will also allow a corollary analysis in which we can begin to develop a risk profile
model in which other population characteristics known to be associated with disease such as sex and ethnicity
can be incorporated. The central hypotheses of the proposed studies are; that retinal ganglion layer thickness,
thalamic and GM volumes predict 10 year disability across MS subtypes, that patients with high genetic load
for gene variants in specific network pathways undergo faster neurodegeneration, and that combinations of
OCT, MRI and genetic load measures may be used to develop clinically meaningful individual predictive scores
for precision medicine.
Aim 1: To determine whether baseline retinal ganglion layer thickness and thalamic and GM volumes predict
10 year disease outcomes.
Aim 2: To determine whether genetic variation, sex and ethnicity influence rates of GCIP, thalamic, GM
atrophy, and disability accumulation.
Aim 3: To develop an algorithm disease progression model to predict disease outcome.
期刊论文(54)
专著(0)
科研奖励(0)
会议论文
Validation of Serum Neurofilament Light Chain as a Prognostic and Monitoring Biomarker in Multiple Sclerosis
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批准号:10543186
-
项目类别:
-
资助金额:$126.22万
-
财政年份:2020
-
负责人:PETER A CALABRESI
-
依托单位:
Validation of Serum Neurofilament Light Chain as a Prognostic and Monitoring Biomarker in Multiple Sclerosis
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批准号:10322766
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项目类别:
-
资助金额:$127.02万
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财政年份:2020
-
负责人:PETER A CALABRESI
-
依托单位:
Imaging neurodegeneration in multiple sclerosis
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批准号:8482285
-
项目类别:
-
资助金额:$43.89万
-
财政年份:2013
-
负责人:PETER A CALABRESI
-
依托单位:
Imaging neurodegeneration in multiple sclerosis
-
批准号:8841026
-
项目类别:
-
资助金额:$44.28万
-
财政年份:2013
-
负责人:PETER A CALABRESI
-
依托单位:
Imaging neurodegeneration in multiple sclerosis
-
批准号:9270631
-
项目类别:
-
资助金额:$35.44万
-
财政年份:2013
-
负责人:PETER A CALABRESI
-
依托单位:
Imaging neurodegeneration in multiple sclerosis
-
批准号:9043962
-
项目类别:
-
资助金额:$35.44万
-
财政年份:2013
-
负责人:PETER A CALABRESI
-
依托单位:
Selective modulation of thyroid hormone receptors to promote remyelination
-
批准号:8426917
-
项目类别:
-
资助金额:$24.3万
-
财政年份:2012
-
负责人:PETER A CALABRESI
-
依托单位:
Selective modulation of thyroid hormone receptors to promote remyelination
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批准号:8554391
-
项目类别:
-
资助金额:$19.54万
-
财政年份:2012
-
负责人:PETER A CALABRESI
-
依托单位:
MECHANISMS OF NEURODEGENERATION AND STRATEGIES FOR NEUROPROTECTION IN MS
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批准号:7602577
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项目类别:
-
资助金额:$3.45万
-
财政年份:2007
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负责人:PETER A CALABRESI
-
依托单位:
ANALYSIS OF THE AXONAL DEGENERATION FOLLOWING INFLAMMATORY DEMYELINATION IN MULT
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批准号:7604738
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项目类别:
-
资助金额:$0.02万
-
财政年份:2006
-
负责人:PETER A CALABRESI
-
依托单位:
ATORVASTATIN THERAPY IN EARLY MULTIPLE SCLEROSIS
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批准号:7604615
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项目类别:
-
资助金额:$0.03万
-
财政年份:2006
-
负责人:PETER A CALABRESI
-
依托单位:
AVONEX COMBINATION TRIAL (ACT)
-
批准号:7604583
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项目类别:
-
资助金额:$0.01万
-
财政年份:2006
-
负责人:PETER A CALABRESI
-
依托单位:
PHASE II/III STUDY OF RITUXIMAB IN ADULTS WITH MS
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批准号:7200813
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项目类别:
-
资助金额:$0.07万
-
财政年份:2005
-
负责人:PETER A CALABRESI
-
依托单位:
AVONEX COMBINATION TRIAL (ACT)
-
批准号:7200776
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项目类别:
-
资助金额:$0.35万
-
财政年份:2005
-
负责人:PETER A CALABRESI
-
依托单位:
ANALYSIS OF THE AXONAL DEGENERATION FOLLOWING INFLAMMATORY DEMYELINATION IN MULT
-
批准号:7378987
-
项目类别:
-
资助金额:$0.08万
-
财政年份:2005
-
负责人:PETER A CALABRESI
-
依托单位:
AVONEX COMBINATION TRIAL (ACT)
-
批准号:7378855
-
项目类别:
-
资助金额:$0.22万
-
财政年份:2005
-
负责人:PETER A CALABRESI
-
依托单位:
MECHANISMS OF NEURODEGENERATION AND STRATEGIES FOR NEUROPROTECTION IN MS
-
批准号:7957329
-
项目类别:
-
资助金额:$3.21万
-
财政年份:2001
-
负责人:PETER A CALABRESI
-
依托单位:
MECHANISMS OF NEURODEGENERATION AND STRATEGIES FOR NEUROPROTECTION IN MS
-
批准号:8364130
-
项目类别:
-
资助金额:$3.75万
-
财政年份:2001
-
负责人:PETER A CALABRESI
-
依托单位:
MECHANISMS OF NEURODEGENERATION AND STRATEGIES FOR NEUROPROTECTION IN MS
-
批准号:8171708
-
项目类别:
-
资助金额:$3.18万
-
财政年份:2001
-
负责人:PETER A CALABRESI
-
依托单位:
MECHANISMS OF NEURODEGENERATION AND STRATEGIES FOR NEUROPROTECTION IN MS
-
批准号:7724142
-
项目类别:
-
资助金额:$2.21万
-
财政年份:2001
-
负责人:PETER A CALABRESI
-
依托单位:
海外基金