Core C
核心C
基本信息
- 批准号:10582720
- 负责人:
- 金额:$ 20.35万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-09-30 至 2025-03-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAmyotrophic Lateral SclerosisAnimalsAntisense OligonucleotidesAutopsyBehaviorBiochemicalBiological MarkersBiological ModelsBrainC9ALSC9FTDC9ORF72Cerebrospinal FluidClinicClinicalClinical ResearchClinical TrialsCognitionCollectionCytoplasmDataDetectionDevelopmentDiagnosticDipeptidesDiseaseDisease ProgressionEnrollmentEvaluationGenesGeneticGenetic TranscriptionGenotypeGliosisHarvestHistopathologyHomeHumanImmunoassayImmunohistochemistryIndividualInduced pluripotent stem cell derived neuronsInvestigationLeadLengthLifeLightLinkMeasuresMethodsMolecularMusMuscle WeaknessMuscular AtrophyNerve DegenerationNeuronal DifferentiationNuclear Pore Complex ProteinsPathologicPathologyPathway interactionsPatientsPeripheralPhenotypePhosphorylationPlasmaPlayProcessProductionPrognosisProteinsProteomeProteomicsRNAResearch PersonnelResearch Project GrantsResourcesRoleSamplingSeriesServicesSpinal CordTestingTherapeuticTissue SampleTissuesTranslationsTreatment outcomeValidationWestern BlottingWorkastrogliosisbench to bedsidebiomarker developmentbrain tissuec9FTD/ALScandidate markereffective therapyfrontotemporal lobar dementia amyotrophic lateral sclerosishuman tissueimprovedinduced pluripotent stem cellinsightmRNA Expressionmemberneurofilamentneuropathologynew therapeutic targetnovel markerparticipant enrollmentpatient stratificationpharmacodynamic biomarkerprotein TDP-43successsurvival predictiontherapeutic biomarkertherapeutic targettraittranscriptometranscriptomicsvalidation studies
项目摘要
PROJECT SUMMARY/ABSTRACT: CORE C
G4C2 repeat expansions in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (ALS)
and frontotemporal dementia (FTD), two devastating diseases with no effective treatment. Success in
developing a treatment for “c9ALS/FTD” will require a better understanding of disease pathomechanisms, the
identification of molecular pathways amenable to therapeutic targeting, and the development of biomarkers to
track disease progression and to confirm target engagement of potential therapies. The studies outlined in
Projects 1, 2 and 3 aim to fill these needs, and the Human Validation Core (Core C) will work closely with
Project investigators to facilitate these important studies. In addition to providing post-mortem tissues to
Projects 1, 2 and 3, Core C will conduct a thorough neuropathological and biochemical analysis of these
patient samples, including the quantification of TDP-43, P62 and dipeptide repeat (DPR) protein pathology,
microgliosis and astrogliosis, and repeat length. Core C will similarly characterize brain tissues from (G4C2)149
mice used in Projects 1 and 3, and measure DPR protein levels in neurons differentiated from patient-derived
induced pluripotent stem cells used in Project 2. These data will serve as valuable traits for the proteomic and
transcriptomic studies conducted in all three projects to discover pathological mechanisms relevant to disease,
and biomarkers for use in clinical trials. Furthermore, Core C will play a significant role in validating, at the
protein level, expression changes of genes or proteins that associate with ALS genotypes or phenotypes, and
that may define pathophysiological pathways linked to c9ALS. This will be done with independent methods of
protein detection and using tissues from discovery series and validation series. Indeed, to ensure that the
collection of post-mortem tissues from C9orf72 repeat expansion carriers continues to grow, Core C will work
closely with Core B to obtain rapid autopsies of patients enrolled in clinical studies and provide diagnostic
evaluations. In this fashion, we will further increase the number of patients from whom both antemortem
cerebrospinal fluid (CSF) and postmortem brain tissue are available – important resources for comparing brain
and CSF proteomes. With regards to the latter, Core C will help Project 3 home in on promising candidate
biomarkers that warrant investigation in CSF, and assist in determining whether their top candidates could
serve as CSF biomarkers for c9ALS/FTD.
项目摘要/摘要:核心c
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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Tania France Gendron其他文献
Tania France Gendron的其他文献
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{{ truncateString('Tania France Gendron', 18)}}的其他基金
Poly(ADP-ribose) promotes the condensation and toxicity of C9orf72 arginine-rich dipeptide repeat proteins
聚(ADP-核糖)促进 C9orf72 富含精氨酸的二肽重复蛋白的缩合和毒性
- 批准号:
10707931 - 财政年份:2021
- 资助金额:
$ 20.35万 - 项目类别:
Poly(ADP-ribose) promotes the condensation and toxicity of C9orf72 arginine-rich dipeptide repeat proteins
聚(ADP-核糖)促进 C9orf72 富含精氨酸的二肽重复蛋白的缩合和毒性
- 批准号:
10298581 - 财政年份:2021
- 资助金额:
$ 20.35万 - 项目类别:
Poly(ADP-ribose) promotes the condensation and toxicity of C9orf72 arginine-rich dipeptide repeat proteins
聚(ADP-核糖)促进 C9orf72 富含精氨酸的二肽重复蛋白的缩合和毒性
- 批准号:
10448297 - 财政年份:2021
- 资助金额:
$ 20.35万 - 项目类别:
Frontotemporal dementia and related disorders: transcriptomic profiling, biomarker discovery, and mechanistic insight
额颞叶痴呆及相关疾病:转录组分析、生物标志物发现和机制洞察
- 批准号:
10392505 - 财政年份:2021
- 资助金额:
$ 20.35万 - 项目类别:
Frontotemporal dementia and related disorders: transcriptomic profiling, biomarker discovery, and mechanistic insight
额颞叶痴呆及相关疾病:转录组分析、生物标志物发现和机制洞察
- 批准号:
10180652 - 财政年份:2021
- 资助金额:
$ 20.35万 - 项目类别:
Frontotemporal dementia and related disorders: transcriptomic profiling, biomarker discovery, and mechanistic insight
额颞叶痴呆及相关疾病:转录组分析、生物标志物发现和机制洞察
- 批准号:
10597677 - 财政年份:2021
- 资助金额:
$ 20.35万 - 项目类别:
Pathologically modified TDP-43 in neurodegenerative diseases
病理修饰的 TDP-43 在神经退行性疾病中的应用
- 批准号:
8263381 - 财政年份:2011
- 资助金额:
$ 20.35万 - 项目类别:
Pathologically modified TDP-43 in neurodegenerative diseases
病理修饰的 TDP-43 在神经退行性疾病中的应用
- 批准号:
8093934 - 财政年份:2011
- 资助金额:
$ 20.35万 - 项目类别:
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