课题基金 / 基金详情

GM-CSF/sargramostim treatment to improve cognition in Down syndrome

GM-CSF/sargramostim treatment to improve cognition in Down syndrome
GM-CSF/沙格司亭治疗可改善唐氏综合症的认知能力
批准号:
10304446
负责人:
Huntington Potter
金额:
$34.55万
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
已结题
起止时间:
2021-09-30 至 2023-08-31
关键词:
Activities of Daily LivingAdolescentAdultAdverse effectsAgeAge-associated memory impairmentAlzheimer&aposs DiseaseAlzheimer&aposs disease brainAlzheimer&aposs disease modelAlzheimer&aposs disease pathologyAlzheimer&aposs disease patientAmyloidAmyloid beta-Protein PrecursorAmyloidosisAnimal ModelApoptoticBiological MarkersBloodBlood specimenBone MarrowBrain PathologyCerebellumCerebrumChildClinical TrialsCognitionCognitiveCommunitiesDataDementiaDoseDouble-Blind MethodDown SyndromeEmploymentExhibitsFDA approvedFloorGene ProteinsGlial Fibrillary Acidic ProteinGranulocyte-Macrophage Colony-Stimulating FactorHippocampus (Brain)HumanImpaired cognitionIncidenceIndividualIntellectual functioning disabilityLanguageLeukocytesLinguisticsLiving WillsLongevityMeasuresMemoryModalityMusNerve DegenerationNervous System TraumaNeurologistNeuronsOutcome MeasureParkinson DiseaseParticipantPatientsPersonsPharmaceutical PreparationsPhase II Clinical TrialsPhase II/III TrialPhenotypePlacebosPlasmaProductionQuality of lifeRandomizedRecombinantsRecording of previous eventsResearchResearch PersonnelRetrospective StudiesSafetySpinal cord injurySubcutaneous InjectionsTauopathiesTestingTherapeuticTraumatic Brain InjuryTreatment FactorVisitVulnerable PopulationsWild Type MouseWorkagedamyloid pathologyastrogliosisbasecerebral amyloidosischemobraincirculating biomarkerscognitive abilitycognitive benefitscognitive enhancementcognitive functioncognitive performancecognitive testingdesignenhancing factorexecutive functionexperiencefollow-upfrontal lobehematopoietic cell transplantationimprovedleukemiameetingsmental statemotor controlmouse modelmultidisciplinarynervous system disorderneuroinflammationnormal agingnovel therapeuticspatient populationprimary endpointprimary outcomeprocessing speedsafety testingsargramostimsecondary outcomesevere intellectual disabilitysingle moleculestroke modelsubcutaneoustau Proteinstreatment durationyoung adult

项目摘要

项目成果

Huntington Potter的其他基金

相似基金

相关文献

中文摘要
翻译
项目总结/文摘
英文摘要
PROJECT SUMMARY/ABSTRACT People with Down syndrome (DS) exhibit significant hypoplasia of the frontal lobe, hippocampus, and cerebellum and mild to severe intellectual disability, which challenges their ability to function independently. Any enhancement of their cognitive ability would greatly improve their quality of life and activities of daily living, but currently there are no therapeutics available for enhancing cognitive function in people with DS. This proposal aims to design and complete a clinical trial in adults with DS using recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF/sargramostim), an FDA-approved drug for increasing the production and differentiation of various white blood cells with almost 30 years of excellent safety history in numerous patient populations. In a previous retrospective study, we found that sargramostim treatment is associated with cognitive improvements in leukemia patients after bone marrow chemoablation and hematopoietic cell transplantation. In a recently concluded Phase II clinical trial (NCT01409915), we found that three weeks of sargramostim treatment was safe and well tolerated in mild-to-moderate Alzheimer’s disease (AD) participants and was associated with improvement in the MMSE, reduced biomarkers of neurodegeneration (Tau and UCH-L1), but no evidence of reduced amyloid. Furthermore, we have found that treatment with murine GM-CSF improves cognition and ameliorates astrogliosis in a mouse model of DS (which has no AD pathology), that it rapidly reverses cognitive impairment and removes some cerebral amyloid pathology in mouse models of AD, and that it improves age- related cognitive decline in aged wild-type mice. Numerous other studies have shown that GM-CSF is neuroprotective, anti-apoptotic, neurogenic, and beneficial in several neurological diseases and injuries, for example, in a clinical trial with Parkinson’s disease subjects and in animal models of stroke, spinal cord injury, and traumatic brain injury. Specifically, this proposal is designed to investigate whether treatment with sargramostim at the FDA-recommended dose is safe and tolerable in adults with DS, whether it can improve measures of cognitive function, quality of life, and activities of daily living, and whether it can reduce the Tau and UCH-L1 biomarkers in the blood that we have shown to evidence neuroinflammation and neurodegeneration in people with DS and to be reduced in AD patients by GM-CSF treatment.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Phase II trial of GM-CSF/sargramostim in Alzheimer's Disease
  • 批准号:
    10335221
  • 项目类别:
  • 资助金额:
    $232.62万
  • 财政年份:
    2021
  • 负责人:
    Huntington Potter
  • 依托单位:
Phase II trial of GM-CSF/sargramostim in Alzheimer's Disease
  • 批准号:
    10534753
  • 项目类别:
  • 资助金额:
    $259.94万
  • 财政年份:
    2021
  • 负责人:
    Huntington Potter
  • 依托单位:
Neuronal dysfunction caused by Abeta inhibition of MT motors
  • 批准号:
    8626688
  • 项目类别:
  • 资助金额:
    $31.03万
  • 财政年份:
    2011
  • 负责人:
    Huntington Potter
  • 依托单位:
Abnormal Low Density Lipoprotein Receptor Localization and Function in AD
  • 批准号:
    8688124
  • 项目类别:
  • 资助金额:
    $31.78万
  • 财政年份:
    2011
  • 负责人:
    Huntington Potter
  • 依托单位:
海外基金