Novel monoclonal antibody for single dose treatment of acute CNS injury
单剂量治疗急性中枢神经系统损伤的新型单克隆抗体
基本信息
- 批准号:10023963
- 负责人:
- 金额:$ 20万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-09-30 至 2023-08-31
- 项目状态:已结题
- 来源:
- 关键词:AccelerometerAchievementAcuteAmericanAnimal ModelAnimalsAnti-Anxiety AgentsAntibodiesAnticoagulantsAnticonvulsantsAntidepressive AgentsBasement membraneBiochemicalBrainBrain InjuriesBrain PathologyCD8B1 geneCellsCellular AssayCerebral hemisphere hemorrhageCerebrumCessation of lifeChemosensitizationClinicalClinical TrialsCognitiveCognitive TherapyComplexCortical ContusionsDoseEmergency department visitEndothelial CellsEpitopesExtravasationFDA approvedFamily RelationshipFamily suidaeFreezingGlioblastomaHematomaHospitalizationHourImmuneImmune systemIn VitroInfiltrationInjuryIntegrin alpha4Integrin alpha4beta1IntegrinsInterventionIntracranial PressureIntravenousIschemiaLeptomeningesLeukocytesLifeLigand BindingLigandsLong-Term EffectsLymphocyteMagnetic Resonance ImagingMaximum Tolerated DoseMediatingMedical Care CostsModelingMolecularMonoclonal AntibodiesNervous System TraumaNeurologic DysfunctionsOccupationalOperative Surgical ProceduresPTPRC genePathologyPatientsPatternPediatric HospitalsPeripheralPharmaceutical PreparationsPharmacodynamicsPharmacologyPharmacotherapyPhasePhase I Clinical TrialsPhiladelphiaPlayPreventionProductionQuality of lifeRecurrenceRehabilitation therapyRoleSafetySeveritiesSiteSkull FracturesSmall Business Technology Transfer ResearchSpeechStrokeStructure of choroid plexusTherapeuticTissuesTranslatingTraumaTraumatic Brain InjuryTreatment ProtocolsVascular Cell Adhesion Molecule-1actigraphyanimal efficacycareercentral nervous system injurycerebral hemodynamicschemokinecontrolled cortical impactcranium plastic repaircross reactivitycytokinedisabilityeconomic impactefficacy studyemergency settingsfirst responderhumanized monoclonal antibodiesimmune activationin vivoinhibitor/antagonistmortalitynatalizumabneurobehavioralneuroimagingneutrophilnonhuman primatenovelphase 2 studypreventprimary outcomepsychosocialreceptorrecruitsecondary outcomestandard of caresymptom managementtreatment armtreatment optimizationventricular system
项目摘要
PROJECT SUMMARY
Traumatic brain injury (TBI) represents a significant societal and economic impact. To date, there are no FDA-
approved pharmacotherapies to prevent or reverse TBI. The standard of care in an emergency setting focuses
first on stabilizing the patient and secondly on management of cerebral hemodynamics. The patient may undergo
surgery to remove hematomas, repair skull fractures, and relieve intracranial pressure. Pharmacological
interventions are aimed at symptom management and may include anticoagulants, anticonvulsants, anxiolytics,
and antidepressants. Ultimately, the current approaches to treating TBI are ameliorative and do not mitigate the
biochemical insult that is the cause of brain damage. Hence, there is a significant unmet need for
pharmacological agents to limit or prevent secondary neurological damage associated with TBI. TBI is a multi-
system pathology with complex interactions between the brain, the periphery, and the immune system. In recent
years, mounting evidence from both TBI patients and animal models of brain injury suggest a critical role for
peripheral immune activation in the potentiation of TBI-induced neurological dysfunction and brain pathology.
Importantly, cerebral invasion of lymphocytes crucially depends on the interaction of the leukocyte very late
antigen-4 (VLA-4; integrin α4β1) with vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells. However,
other β1 integrins may also be involved, creating a potential escape mechanism. Hence, targeting multiple β1
integrins which may mediate leukocyte invasion of the CNS has therapeutic potential to limit or prevent
secondary neurological damage associated with TBI. OncoSynergy has developed OS2966, a proprietary, first-
in-class humanized monoclonal pan-CD29/β1 integrin/ITGB1 antibody. Our IND-enabling studies demonstrated
that repeat weekly intravenous dosing of OS2966 is well tolerated in non-human primates with no mortality,
clinical signs, gross pathology, or maximum tolerated dose (MTD) reached (up to 35 mg/kg). In March 2019,
FDA cleared our IND to initiate a Phase I clinical trial in patients with recurrent glioblastoma using intracerebral
delivery of OS2966. The known pharmacology and safety profiles of OS2966 provide a strong support to quickly
translate this drug to clinical trials for TBI, upon the successful completion of the proof-of-concept study. Hence,
we propose to collaborate with Dr. Todd Kilbaugh at Children's Hospital of Philadelphia to conduct this Phase I
STTR project to evaluate the efficacy of OS2966 in a high-fidelity porcine model of TBI. Successful achievement
of this Phase I STTR project will enable further Phase II studies to optimize the treatment regimen of OS2966 in
multiple porcine models of TBI and advance OS2966 to Phase 2 proof of concept efficacy studies in TBI patients.
项目总结
项目成果
期刊论文数量(0)
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Anne-Marie Carbonell其他文献
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{{ truncateString('Anne-Marie Carbonell', 18)}}的其他基金
Novel monoclonal antibody for single dose treatment of acute CNS injury
单剂量治疗急性中枢神经系统损伤的新型单克隆抗体
- 批准号:
9908197 - 财政年份:2019
- 资助金额:
$ 20万 - 项目类别:
Oncolytic virus-mediated target delivery of a therapeutic antibody fragment in glioblastoma
溶瘤病毒介导的胶质母细胞瘤治疗抗体片段的靶向递送
- 批准号:
9908664 - 财政年份:2019
- 资助金额:
$ 20万 - 项目类别:
Novel monoclonal antibody for single dose treatment of acute CNS injury
单剂量治疗急性中枢神经系统损伤的新型单克隆抗体
- 批准号:
10164043 - 财政年份:2019
- 资助金额:
$ 20万 - 项目类别:
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