BLR&D MERIT REVIEW RESEARCH CAREER SCIENTIST AWARD APPLICATION
BLR
基本信息
- 批准号:10701474
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-04-01 至 2028-03-31
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAfghanistanAgeAgingAlzheimer&aposs DiseaseAmputationAmyotrophic Lateral SclerosisAnimal ModelAwardBiologyBlindnessBrainBrain InjuriesCapsidCardiacCaveolinsCellsCentral Nervous SystemCentral Nervous System DiseasesCerebrumChronicCirculationClinicalCognitiveCyclic AMPCytoskeletonDiseaseDoseElderlyEngineeringEnhancing LesionExhibitsFaceFamilyFellowshipFinancial HardshipFundingG Protein-Coupled Receptor SignalingGene DeliveryGeneticGoalsGrantGrowthHeadHealthHealth Care CostsHealthcare SystemsHippocampusHumanIn VitroIndividualInduced pluripotent stem cell derived neuronsInjuryInterventionIraqJournalsKnowledgeLaboratoriesLearningLegal patentLongevityMedical Care CostsMembraneMembrane MicrodomainsMembrane ProteinsMemoryMental DepressionMethamphetamineMitochondriaModelingMolecular TargetMorbidity - disease rateMorphologyMotorMotor NeuronsMultiple TraumaMusNational Institute of Neurological Disorders and StrokeNerve DegenerationNerve Growth Factor ReceptorsNervous System PhysiologyNeurodegenerative DisordersNeuromuscular JunctionNeuronal PlasticityNeuronsNeurotransmitter ReceptorOnset of illnessOutpatientsPaperPatientsPhysical RehabilitationPost-Traumatic Stress DisordersPostdoctoral FellowPreventionPrincipal InvestigatorProteinsPublishingRattusResearchResearch Peer ReviewResearch PersonnelRisk FactorsRouteScaffolding ProteinScientistSeminalSenile PlaquesSignal TransductionSpinalSpinal CordState GovernmentSynapsesSynapsinsSynaptic plasticityTherapeuticTimeTransgenic MiceTranslatingTraumaTraumatic injuryTreatment EfficacyTropismUnited StatesUnited States Department of Veterans AffairsVertebral columnVeteransWarWorkage related neurodegenerationagedcareercaveolin 1cholesterol-binding proteincognitive functioncomorbiditycostfamilial amyotrophic lateral sclerosisfunctional plasticityfunctional restorationgene therapyhigh riskimprovedin vitro Modelin vivoinjuredischemic injurymiddle agemilitary servicemilitary veteranmitochondrial dysfunctionmotor function improvementmouse modelmutantneuroinflammationneuromuscular functionneuroprotectionneurotransmissionneurotrophic factornoveloverexpressionpharmacologicpreservationpromoterreceptor-mediated signalingsocialsocial rehabilitationspinal cord and brain injurysporadic amyotrophic lateral sclerosissynaptic functiontheranosticstrend
项目摘要
Age-related neurodegenerative diseases such as Alzheimer’s disease (AD) and amyotrophic lateral sclerosis
(ALS) are the most common cause of morbidity in the Veteran population. Medical costs for U.S. Veterans of
Iraq and Afghanistan could be enormous because of differences between these wars and previous conflicts
due to today’s Veterans surviving injuries that would have been fatal in previous wars, and "polytraumatic"
injuries that require decades of costly physical and social rehabilitation. With no prevention or treatment,
individuals with neurodegenerative conditions could reach 11-16 million by 2050. In addition to age-related
neurodegeneration, depression among the elderly has been estimated to increase health care costs by 50%
and increase outpatient costs by 43 to 52% in these individuals compared to non-depressed patients. With this
growing Veteran population is an increase in chronic health conditions, and social and financial burdens on
their families and the health care system. Neurodegeneration diseases are closely associated with decreased
neuronal signaling, mitochondrial dysfunction, loss of synapses and neuromuscular junctions. Since receiving
the VA CDA in 2009, the Head laboratory has focused on targeting molecular mechanisms (via genetic and/or
pharmacologic interventions) to evoke functional neuronal and synaptic plasticity to improve cognitive and
motor function in the neurodegenerative brain and spinal cord respectively. As a result of continuous funding
from the VA (3 Merits since 2011) and NIH (NINDS R01 2011), in 2012 Dr. Head was bestowed the
Presidential Early Career Awards for Scientists and Engineers (PECASE) through the Department of Veterans
Affairs, which is the highest honor given by the United States Government to early-stage scientist and
engineers. Specifically, the Head laboratory investigates how caveolin (Cav), a cholesterol binding and
scaffolding protein within membrane/lipid rafts (MLRs), regulates synaptic signaling, mitochondrial function,
and neuroplasticity in neuronal models in vitro using human neurons derived from iPSCs and in animal models
of neurodegeneration such as AD and ALS. Cav-1 is a cholesterol-binding and membrane protein that is
essential for MLR formation and MLR-localization of neurotrophin receptors and synaptic proteins necessary
for synaptic function and neuroplasticity. Dr. Head engineered a genetic construct that contains a neuron-
targeted promoter (synapsin) to drive the expression of Cav-1 (termed SynCav1) specifically in neurons to
evoke neuroprotection and functional plasticity in the setting of disease or following traumatic injury (work
funded by NINDS, VA, and DoD). Dr. Head patented this novel gene therapy through the U.S. Patent Office in
March 2015 (U.S. Patent No. 8,969,077 B2: Neuronal specific targeting of caveolin expression to restore
synaptic signaling and improve cognitive function in the neurodegenerative brain and motor function in spinal
cord) of which the VA and UCSD are owners. The Head laboratory published several seminal studies
demonstrating that exogenous delivery of SynCav1 (using AAV9) promotes hippocampal synaptic and
neuroplasticity, significantly improves learning and memory in aged mice and in AD mice, the latter
independent of reducing amyloid plaques. More recently, Dr. Head’s group showed that spinal cord delivery of
AAV9-SynCav1 protects and preserves spinal motor neuron and neuromuscular junction morphology, motor
function, delays disease onset, and extends longevity in a mouse model of familial (F)ALS, without reducing
the toxic monogenic component (mutant hSOD1). Furthermore, SynCav1 delivery preserved neuromuscular
function in a rat model of FALS. The latter findings strongly indicate the therapeutic applicability of SynCav1 to
treat ALS attributed to monogenic (FALS) and potentially in sporadic cases (i.e., SALS). Dr. Head’s long-term
goal is to translate this gene therapy to the clinical setting to treat Veterans suffering from neurodegenerative
conditions such as AD and ALS.
与年龄相关的神经退行性疾病,如阿尔茨海默病(AD)和肌萎缩侧索硬化症
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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BRIAN P HEAD其他文献
BRIAN P HEAD的其他文献
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{{ truncateString('BRIAN P HEAD', 18)}}的其他基金
Neuron-targeted caveolin-1 as a gene therapy for ALS
神经元靶向的 Caveolin-1 作为 ALS 的基因疗法
- 批准号:
10625824 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Neuron-targeted caveolin-1 as a gene therapy for ALS
神经元靶向的 Caveolin-1 作为 ALS 的基因疗法
- 批准号:
10027254 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Caveolin-mediated neuronal signaling in differentiated adult human neuronal stem cells and the aging brain
分化的成人神经元干细胞和衰老大脑中小窝蛋白介导的神经元信号传导
- 批准号:
9898275 - 财政年份:2017
- 资助金额:
-- - 项目类别:
Caveolin-Mediated Neuroplasticity in Alzheimer's Disease and in Human Neurons Harboring EOFAD Mutations
Caveolin 介导的阿尔茨海默病和携带 EOFAD 突变的人类神经元的神经可塑性
- 批准号:
10398113 - 财政年份:2017
- 资助金额:
-- - 项目类别:
Caveolin-Mediated Neuroplasticity in Alzheimer's Disease and in Human Neurons Harboring EOFAD Mutations
Caveolin 介导的阿尔茨海默病和携带 EOFAD 突变的人类神经元的神经可塑性
- 批准号:
10247378 - 财政年份:2017
- 资助金额:
-- - 项目类别:
Caveolin-mediated neuronal signaling in differentiated adult human neuronal stem cells and the aging brain
分化的成人神经元干细胞和衰老大脑中小窝蛋白介导的神经元信号传导
- 批准号:
9349907 - 财政年份:2017
- 资助金额:
-- - 项目类别:
Caveolin-Mediated Neuroplasticity in Alzheimer's Disease and in Human Neurons Harboring EOFAD Mutations
Caveolin 介导的阿尔茨海默病和携带 EOFAD 突变的人类神经元的神经可塑性
- 批准号:
10620148 - 财政年份:2017
- 资助金额:
-- - 项目类别:
Neuron-Targeted Caveolin-1 as a Therapy for Age-Related Neurodegeneration
神经元靶向 Caveolin-1 作为年龄相关神经退行性疾病的治疗方法
- 批准号:
8330529 - 财政年份:2012
- 资助金额:
-- - 项目类别:
Neuron-Targeted Caveolin-1 as a Therapy for Age-Related Neurodegeneration
神经元靶向 Caveolin-1 作为年龄相关神经退行性疾病的治疗方法
- 批准号:
8698261 - 财政年份:2012
- 资助金额:
-- - 项目类别:
Neuron-Targeted Caveolin-1 as a Therapy for Age-Related Neurodegeneration
神经元靶向 Caveolin-1 作为年龄相关神经退行性疾病的治疗方法
- 批准号:
8452592 - 财政年份:2012
- 资助金额:
-- - 项目类别:
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