Modulation of FcRn: A strategy to prevent autoantibody-mediated nerve injury
FcRn 的调节:预防自身抗体介导的神经损伤的策略
基本信息
- 批准号:8684787
- 负责人:
- 金额:$ 19万
- 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:2014-04-01 至 2016-03-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAffinityAnimal ModelAnimalsAntibodiesAntigen TargetingAntigen-Antibody ComplexApplications GrantsAreaArthritisAutoantibodiesAutoimmune DiseasesAutoimmune ProcessAutoimmune ResponsesAxonBindingBlood-Nerve BarrierCell surfaceClinicalClinical TrialsClinical Trials DesignComplementDataDevelopmentDiseaseDisease modelEngineeringEnhancing AntibodiesEthicsFutureGangliosidesGlycosphingolipidsGrantGuillain-Barré SyndromeHalf-LifeHumanIgG ReceptorsIgG1ImmuneImmune systemImmunoglobulin GImmunotherapyInflammationInjuryIntravenous ImmunoglobulinsLeftMeasuresMediatingModalityModelingMusMyasthenia GravisNatural regenerationNeonatalNerve CrushNerve FibersNeurologicNeuromyelitis OpticaNeuropathyParalysedPathogenicityPathologyPatientsPeripheral NervesPharmaceutical PreparationsPhasePoliomyelitisPolysaccharidesPre-Clinical ModelPropertyPublishingRanvier&aposs NodesRecoveryResearchRoleScheduleSialic AcidsSurfaceSyndromeTestingTherapeuticTherapy EvaluationTransgenic MiceUp-RegulationVariantWalkingantibody engineeringaxon regenerationbasecomparative efficacydesigninjuredneonatal Fc receptornerve injurynovel therapeuticspreventpublic health relevancerandomized placebo controlled trialrepairedresearch studysynergismtranslational approachtreatment strategyward
项目摘要
Abstract
With the near-eradication of polio, Guillain-Barr¿ syndrome (GBS) has become the most frequent cause of
acute flaccid paralysis. Current immunomodulatory treatments are only effective in a proportion of patients. For
example IVIG-a first line treatment modality in GBS-hasten recovery in only ~50% of those treated with this
medication. Despite availability of current of immunotherapies, a significant proportion of patients are left with
severe and permanent neurologic sequelae, including inability to walk independently. There is a dire need for
newer/additional treatments that can limit the axonal damage during the acute phase of the disease and
enhance repair during recovery period are desirable. For over last 20 years no new treatments have entered
the clinical arena of GBS. It is in this context we want to test an Abdeg (Fc-engineered antibody that enhance
IgG degradation by blocking neonatal Fc receptor (FcRn)) appropriate for human use as autoAb-specific
immunotherapy in preclinical models of GBS. Anti-ganglioside antibodies (Abs) are the most frequently
recognized autoimmune responses in GBS. We focus on anti-glycan Ab associated disease models in this
grant as substantial experimental data support the primary pathogenic role of these autoAbs in GBS
particularly in its axonal variants. Our group has developed two different passive transfer animal models with
anti-glycan Abs, which will be used in the proposed studies. Our preliminary studies show that mice lacking
neonatal Fc receptor (FcRn) are not susceptible to anti-ganglioside Ab-mediated nerve injury due to rapid
clearance of these Abs in an animal model. Based on these observations we postulate that Abdegs would be
protective in our animal models of anti-ganglioside Ab-mediated nerve injury. This hypothesis will be tested by
the following specific aims: Aim 1 will examine the efficacy of Abdeg (MST-HN) in animal studies by measuring
the circulating half-life of pathogenic experimental and human anti-glycan Abs and correlate this with their
pathogenic effects on intact and injured axons; Aim 2 will compare efficacy and/or synergism of IVIG with
Abdeg MST-HN in suppressing anti-glycan Ab-mediated nerve injury in animal models. For translational
purposes it would be important to determine in preclinical models whether a): Abdeg (MST-HN) and IVIG do
not have antagonistic effects; and b) these two medications have synergistic effects. Both these issues are
relevant from ethical and trial design perspective if this therapy were to extend to human studies. This project
may help in developing new treatment stratgies aiming to expedite clearnce of autoAbs and has relevance not
only to GBS but other neuroimmunological disorders including myasthenia gravis and neuromyelitis optica.
摘要
项目成果
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KAZIM A SHEIKH其他文献
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{{ truncateString('KAZIM A SHEIKH', 18)}}的其他基金
Blockade of colony stimulating factor 1 receptor to reduce inflammatory nerve injury
阻断集落刺激因子 1 受体以减少炎症神经损伤
- 批准号:
10195632 - 财政年份:2021
- 资助金额:
$ 19万 - 项目类别:
Modulation of FcRn: A strategy to prevent autoantibody-mediated nerve injury
FcRn 的调节:预防自身抗体介导的神经损伤的策略
- 批准号:
8806622 - 财政年份:2014
- 资助金额:
$ 19万 - 项目类别:
Non-Invasive Imaging to Quantify Peripheral Nerve Injury and Repair in Clinic
无创成像在临床上量化周围神经损伤和修复
- 批准号:
8446439 - 财政年份:2011
- 资助金额:
$ 19万 - 项目类别:
Non-Invasive Imaging to Quantify Peripheral Nerve Injury and Repair in Clinic
无创成像在临床上量化周围神经损伤和修复
- 批准号:
8245788 - 财政年份:2011
- 资助金额:
$ 19万 - 项目类别:
Non-Invasive Imaging to Quantify Peripheral Nerve Injury and Repair in Clinic
无创成像在临床上量化周围神经损伤和修复
- 批准号:
8106764 - 财政年份:2011
- 资助金额:
$ 19万 - 项目类别:
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