Complement inhibitors targeted to the ischemic brain for the treatment of stroke
针对缺血性大脑的补体抑制剂用于治疗中风
基本信息
- 批准号:9316844
- 负责人:
- 金额:$ 34.53万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-04-15 至 2019-03-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAdverse effectsAffectAgeAlteplaseAnnexin A4AntibodiesAutomobile DrivingBindingBiotechnologyBrainCause of DeathCerebral IschemiaCerebrovascular systemCerebrumChronicClinical TrialsCognitiveComplementComplement 3d ReceptorsComplement ActivationComplement InactivatorsDataDevelopmentDoseEligibility DeterminationEmergency MedicineEventFemaleFoundationsFundingFutureGenerationsGoalsHalf-LifeHost DefenseHourHumanHybridomasImmunoglobulin MImmunosuppressive AgentsImpairmentInflammationInjuryInstitutionIntellectual PropertyIpsilateralIschemiaIschemic Brain InjuryIschemic StrokeLaboratoriesLectinLegal patentLicensingLinkMediatingMiddle Cerebral Artery OcclusionModelingMolecularMotorMusNerve RegenerationOutcomeOutcome MeasurePathogenicityPathologyPathway interactionsPatientsPatternPharmaceutical PreparationsPharmacologyPhasePhospholipidsPhysiciansPhysiologicalPlasminogen ActivatorPlayQuality ControlRag1 MouseReagentRecombinantsRecovery of FunctionRegimenReperfusion InjuryReperfusion TherapyResearchRiskRoleSamplingScheduleScientistSecureSeriesSiteStrokeSymptomsTechnologyTestingTimeTissuesUnited Statesagedcentral nervous system injurycognitive recoverycommercializationcomplement pathwaycomplement systemdisabilitydrug developmentexperienceexperimental studyfunctional outcomesimprovedin vitro Assayinhibitor/antagonistinjury and repairmouse modelmultidisciplinarynovelnovel strategiespost strokepre-clinicalprogramsreconstitutionrepairedresearch and developmentresponsestandard of carestroke therapystroke treatmenttherapeutic development
项目摘要
Recombinant tissue-type plasminogen activator (tPA) is currently the only approved pharmacological agent for
the treatment of ischemic stroke, and in general it must be administered within 4.5 hours of symptom onset.
Because of this time constraint, as well as dangers associated with this drug, it is estimated that only about 5-
10% of stroke patients are treated with tPA. There is thus a significant need for new and effective approaches
to treat stroke. It is now clear that the complement system plays an important role in the propagation of
inflammation and injury following cerebral ischemia and reperfusion (ischemic stroke), and the overall goal of
this project is to develop and characterize a novel, effective and safe strategy of site-targeted complement
inhibition that can be applied several hours after stroke, and that will improve long-term cognitive and
functional recovery. To identify the most effective complement inhibitory approach, we will prepare and
characterize various complement inhibitors that block different parts of the complement pathway and that are
targeted to the site of ischemic brain injury via a novel approach. The constructs will be investigated using a
mouse model of middle cerebral artery occlusion and reperfusion, and we will investigate the effect of our
constructs on cerebral injury, repair and neuroregeneration, and acute and chronic cognitive and motor
function outcomes. Following identification of the optimum type of complement inhibitory construct, we will
complete a series of pre-clinical determinations that will assist in future drug development. These studies will
include PK and PD determinations, dose response, treatment window, dosing schedule, and effect in young
and aged mice (since the risk of stroke increases with age). Finally, we will investigate our strategy of
complement inhibition in the context of tPA therapy to determine whether there are any adverse effects
associated with co-administration of the two pharmacological reagents.
重组组织型纤溶酶原激活剂(tPA)是目前唯一被批准的药物
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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Stephen Tomlinson其他文献
Stephen Tomlinson的其他文献
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{{ truncateString('Stephen Tomlinson', 18)}}的其他基金
The role of complement in chronic neuroinflammation and cognitive decline after closed head brain injury
补体在闭合性脑损伤后慢性神经炎症和认知能力下降中的作用
- 批准号:
10641096 - 财政年份:2023
- 资助金额:
$ 34.53万 - 项目类别:
BLR&D Research Career Scientist Award Application for Dr. Stephen Tomlinson
BLR
- 批准号:
10618250 - 财政年份:2020
- 资助金额:
$ 34.53万 - 项目类别:
BLR&D Research Career Scientist Award Application for Dr. Stephen Tomlinson
BLR
- 批准号:
10451506 - 财政年份:2020
- 资助金额:
$ 34.53万 - 项目类别:
Cell survival in engineered skeletal muscle: The role of complement
工程骨骼肌中的细胞存活:补体的作用
- 批准号:
10189582 - 财政年份:2019
- 资助金额:
$ 34.53万 - 项目类别:
Cell survival in engineered skeletal muscle: The role of complement
工程骨骼肌中的细胞存活:补体的作用
- 批准号:
10017965 - 财政年份:2019
- 资助金额:
$ 34.53万 - 项目类别:
Cell survival in engineered skeletal muscle: The role of complement
工程骨骼肌中的细胞存活:补体的作用
- 批准号:
10449327 - 财政年份:2019
- 资助金额:
$ 34.53万 - 项目类别:
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