Myelin oligodendrocyte glycoprotein antibody disease: incidence, prevalence, outcome prediction and immunopathology
髓磷脂少突胶质细胞糖蛋白抗体病:发病率、患病率、结果预测和免疫病理学
基本信息
- 批准号:10531554
- 负责人:
- 金额:$ 34.8万
- 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:2019-12-01 至 2024-11-30
- 项目状态:已结题
- 来源:
- 关键词:Acute Disseminated EncephalomyelitisAntibodiesBiological AssayBiological MarkersBlindnessCase StudyCellsCerebrospinal FluidCharacteristicsChildClassificationClinicClinicalClinical Laboratory Improvement AmendmentsClinical Trials DesignComaComplementComplement InactivatorsDataDecision MakingDemyelinating DiseasesDemyelinationsDependenceDepositionDetectionDevelopmentDiagnosisDiagnosticDiseaseEpidemiologyEvaluationEvolutionFlow CytometryFrequenciesGoalsHarm ReductionHealthcareImmunoglobulin GIncidenceInflammatoryInflammatory InfiltrateKnowledgeLesionMagnetic Resonance ImagingMeasurementMeasuresMissionMultiple SclerosisMultiple Sclerosis LesionsMyelitisNatureNeuromyelitis OpticaOptic NeuritisOutcomeParalysedPathogenesisPathologicPathologyPatient CarePatientsPatternPhasePhysiciansPopulationPrevalenceProcessPrognosisRare LesionResearchResearch ProposalsResource AllocationRetrospective StudiesRisk FactorsSafetySerumTestingTherapeuticUnited States National Institutes of HealthVariantWheelchairsaquaporin 4biobankblindclinical practiceclinical trial readinesscohortdiagnostic valueexperienceimmunopathologyimproved outcomeinnovationinsightnovelnovel therapeuticsoligodendrocyte-myelin glycoproteinoutcome predictionpopulation basedprognostic valueprospectivepublic health relevancerecruitrelapse predictionrelapse riskresource guidesseropositivestandard of caretissue injurytissue repairtreatment strategy
项目摘要
PROJECT SUMMARY/ABSTRACT
Attacks of myelin oligodendrocyte glycoprotein antibody disease (MOGAD) can render a patient blind,
paralyzed or comatose and distinguishing it from other demyelinating diseases such as multiple sclerosis (MS)
and aquaporin-4(AQP4)-IgG positive neuromyelitis optica spectrum disorder (NMOSD) is crucial given the
major differences in clinical course, treatment and prognosis. Major knowledge gaps in MOGAD are hindering
patient care and a barrier to understanding its pathogenesis. The absence of MOGAD incidence and
prevalence data and limited knowledge on its epidemiology worldwide directly impacts decisions on when to
order MOG-IgG, healthcare planning, clinical trial design and identification of risk factors. The lack of
prospective USA data regarding the prognostic value of MOG-IgG titer and persistence impacts treatment
decisions. MOG-IgG in cerebrospinal fluid (CSF) is used by clinicians to diagnose MOGAD, yet data on its
diagnostic utility is limited compared to the established utility of serum MOG-IgG. The limited data on MRI
evolution and immuno-pathology hinders our understanding of MOGAD pathogenesis. The long-term goal is to
better diagnose, treat, and understand MOGAD. The objective of this proposal is to determine the incidence
and prevalence of MOGAD, the prognostic value of MOG-IgG testing, the diagnostic utility of CSF MOG-IgG,
the evolution of MRI lesions and the immunopathology. The central hypotheses (supported by the applicants
preliminary data) is that MOGAD epidemiology is similar to AQP4-IgG in the USA but varies by region, that
serum MOG-IgG persistence and high titer predict relapse, that CSF MOG-IgG lacks diagnostic utility, that
MOGAD MRI lesions resolve more often than MS and that immuno-pathological characteristics of MOGAD can
be defined. The rationale is that these findings will directly impact patient care, facilitate clinical trial readiness,
enhance understanding of pathogenesis, and lead to development of novel treatments. The hypothesis will be
tested by pursuing three specific aims: 1) To determine the population-based incidence, prevalence and
frequency of MOGAD versus AQP4-IgG and MS across multiple world regions; 2) To identify the prognostic
value of MOG-IgG titer and persistence, assess the utility of CSF MOG-IgG and compare MRI evolution to MS
and AQP4-IgG NMOSD; 3) To define the immuno-pathology of MOGAD and compare it to MS and AQP4-IgG
NMOSD. To do this we will utilize the largest clinical, sero-epidemiologic and pathologic biobank of
demyelinating disease in the world. The approach is innovative because it uses a novel live-cell flow cytometry
based MOG-IgG assay developed by the team of applicants. The proposed research is significant because it is
expected to guide resource allocation, directly impact patient care by providing guidance on diagnostics and
therapeutics and give insight into pathogenesis. Ultimately, the knowledge of immunopathology may lead to
the development of novel treatments similar to how complement deposition in AQP4-IgG NMOSD pathology
led to phase 2 and 3 trials showing efficacy and safety of eculizumab (a complement inhibitor).
项目总结/摘要
髓鞘少突胶质细胞糖蛋白抗体病(MOGAD)的发作可使患者失明,
瘫痪或昏迷,并与其他脱髓鞘疾病,如多发性硬化症(MS)
和水通道蛋白-4(AQP 4)-IgG阳性视神经肌病谱系障碍(NMOSD)是至关重要的,
临床过程、治疗和预后的主要差异。MOGAD的主要知识差距阻碍了
患者护理和理解其发病机制的障碍。没有MOGAD发生率,
流行率数据和对全球流行病学的有限了解直接影响到何时
订单MOG-IgG,医疗保健计划,临床试验设计和风险因素的识别。缺乏
关于MOG-IgG滴度和持续性影响治疗的预后价值的前瞻性美国数据
决策临床医生使用脑脊液(CSF)中的MOG-IgG来诊断MOGAD,但关于其
与已建立的血清MOG-IgG的效用相比,诊断效用有限。MRI数据有限
进化和免疫病理学阻碍了我们对MOGAD发病机制的理解。长期目标是
更好地诊断、治疗和理解MOGAD。本提案的目的是确定发病率
MOGAD的患病率、MOG-IgG检测的预后价值、CSF MOG-IgG的诊断实用性,
MRI病变的演变和免疫病理学。核心假设(由申请人支持)
初步数据)是MOGAD流行病学与美国的AQP 4-IgG相似,但因地区而异,
血清MOG-IgG持久性和高滴度预测复发,CSF MOG-IgG缺乏诊断效用,
MOGAD MRI病变比MS更容易消退,MOGAD的免疫病理学特征可以
被定义。理由是这些发现将直接影响患者护理,促进临床试验准备,
增强对发病机制的理解,并导致新治疗方法的开发。假设是
通过追求三个具体目标进行测试:1)确定基于人群的发病率,患病率和
在世界多个地区,MOGAD与AQP 4-IgG和MS的频率; 2)确定预后
MOG-IgG滴度和持久性的值,评估CSF MOG-IgG的效用并比较MRI演变与MS
3)明确MOGAD的免疫病理学特征,并与MS和AQP 4-IgG进行比较
NMOSD。为了做到这一点,我们将利用最大的临床,血清流行病学和病理生物库,
脱髓鞘疾病该方法是创新的,因为它使用了一种新的活细胞流式细胞术
由申请人团队开发的基于MOG-IgG的测定。这项研究之所以重要,是因为
预计将指导资源分配,通过提供诊断指导直接影响患者护理,
治疗方法并深入了解发病机制。最终,免疫病理学的知识可能会导致
开发类似于AQP 4-IgG NMOSD病理学中补体沉积的新型治疗方法
导致2期和3期试验显示依库珠单抗(一种补体抑制剂)的疗效和安全性。
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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Eoin P Flanagan其他文献
Differential diagnosis of suspected multiple sclerosis: an updated consensus approach
疑似多发性硬化的鉴别诊断:一种更新的共识方法
- DOI:
10.1016/s1474-4422(23)00148-5 - 发表时间:
2023-08-01 - 期刊:
- 影响因子:45.500
- 作者:
Andrew J Solomon;Georgina Arrambide;Wallace J Brownlee;Eoin P Flanagan;Maria Pia Amato;Lilyana Amezcua;Brenda L Banwell;Frederik Barkhof;John R Corboy;Jorge Correale;Kazuo Fujihara;Jennifer Graves;Mary Pat Harnegie;Bernhard Hemmer;Jeannette Lechner-Scott;Ruth Ann Marrie;Scott D Newsome;Maria A Rocca;Walter Royal;Emmanuelle L Waubant;Jeffrey A Cohen - 通讯作者:
Jeffrey A Cohen
Eoin P Flanagan的其他文献
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{{ truncateString('Eoin P Flanagan', 18)}}的其他基金
Myelin oligodendrocyte glycoprotein antibody disease: incidence, prevalence, outcome prediction and immunopathology
髓磷脂少突胶质细胞糖蛋白抗体病:发病率、患病率、结果预测和免疫病理学
- 批准号:
10306353 - 财政年份:2019
- 资助金额:
$ 34.8万 - 项目类别:
Myelin oligodendrocyte glycoprotein antibody disease: incidence, prevalence, outcome prediction and immunopathology
髓磷脂少突胶质细胞糖蛋白抗体病:发病率、患病率、结果预测和免疫病理学
- 批准号:
10064015 - 财政年份:2019
- 资助金额:
$ 34.8万 - 项目类别:
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