Integrated Longitudinal Studies to Identify Biomarkers and Therapeutic Strategies for Sturge-Weber Syndrome
识别斯特奇-韦伯综合征生物标志物和治疗策略的综合纵向研究
基本信息
- 批准号:10673820
- 负责人:
- 金额:$ 36.73万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-09-30 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:AffectAnticonvulsantsAspirinAtrophicBiological MarkersBloodBlood VesselsBrainBrain Vascular MalformationBrain imagingCerebral CalcificationCerebrovascular DisordersClinicalClinical TrialsDataDatabasesDiseaseDisease ProgressionEarly DiagnosisEyeFetal DevelopmentFoundationsFutureGNAQ geneGTP-Binding Protein alpha Subunits, GsGlaucomaGliosisGrantHeadacheHemangiomaImageInflammationInflammatoryLeptomeningesLesionLongitudinal StudiesMagnetic Resonance ImagingMeasuresMigraineMutationNeurologic SymptomsOnline SystemsPatientsPharmaceutical PreparationsPlasmaPort-Wine StainProspective StudiesQuality of lifeRadiology SpecialtyRefractoryRetrospective StudiesRiskSamplingSeizuresSkinSpider nevusStructureSturge-Weber SyndromeSurrogate MarkersSymptomsTestingTherapeuticTimeTissuesVeinsVisualizationangiogenesisbiomarker identificationbrain arteriovenous malformationsbrain parenchymacalcificationcerebral cavernous malformationsclinical careclinical predictorsclinical trial readinessdashboarddata integrationdata registrydata visualizationdrug repurposingimaging biomarkerimaging studylongitudinal databasemalformationmemberparticipant enrollmentpatient biomarkerspatient engagementpatient registrypredictive markerpreventrecruitstroke-like episodestroke-like outcomesynergismtool
项目摘要
Sturge-Weber Syndrome (SWS) is a skin, eye, and brain vascular disorder of capillary
angiomas resulting in port wine stain angiomas affecting the skin, angiomas and glaucoma of the
eye, and leptomeningeal angiomas surrounding the brain. In 2013, members of the Brain Vascular
Malformations Consortium (BVMC) co-identified a somatic, activating mutation in the GNAQ gene
(which encodes the G alpha subunit) in affected vascular tissue. This mutation occurs during fetal
development and thus, even with early diagnosis, the vascular malformation is already present
and may not be reversible. However, as with many vascular brain lesions, serious complications
can arise from the effects of the vascular malformation and the surrounding brain parenchyma.
Recently, the Sturge-Weber Foundation (SWF) brought together patients and clinicians to
identify unmet needs for patients. While neurological symptoms including seizures and
headaches are common, stroke-like episodes, severe bouts of seizures, and migraine headaches
were felt to significantly impact patient quality of life. Current treatments used to prevent these
symptoms include aspirin and seizure medications, but neither is well supported by longitudinal
studies. Nor is it clear exactly what causes stroke-like symptoms or how to identify SWS patients
at risk for these symptoms. Elegant serial brain imaging studies from our previous grant period
have provided important clues showing changes in the vascular structures themselves as well as
surrounding brain parenchyma, including dense brain calcifications that could underlie these
symptoms. Hence, another potentially exciting treatment is to target brain calcifications through a
repurposed drug. Here, we will address pressing needs for clinical trial readiness through the
identification of at risk patients, analysis of current treatments, and identification of robust,
clinically useful and predictive biomarkers.
We plan to extend our patient registry data to integrate longitudinal clinical, radiological, and
blood biomarkers of patients to identify those at most risk to have severe neurological symptoms
and to identify potential treatments (Aim 1). We will identify imaging biomarkers that will change
over time and correlate with severe neurological symptoms (Aim 2). Finally, for enrolled patients
who present with severe neurological symptoms, plasma samples will be screened for
inflammatory changes at baseline, during, and after the severe symptoms to identify predictive
biomarkers for clinical trials (Aim 3). A major deliverable will be a clinically useful, integrated
longitudinal database and dashboard tool to help visualize data that will help clinicians better
understand progression of disease course following the SWS mutation.
Sturge-Weber综合征(SWS)是毛细管的皮肤,眼睛和脑血管疾病
血管瘤导致港口葡萄染色血管瘤影响皮肤,血管瘤和青光眼的血管瘤
眼睛和大脑周围的瘦脑血管瘤。 2013年,脑血管成员
畸形联盟(BVMC)共同识别了GNAQ基因中的体细胞激活突变
(编码Gα亚基)在受影响的血管组织中。这种突变发生在胎儿期间
因此,即使有早期诊断,血管畸形也已经存在
并且可能不是可逆的。但是,与许多血管脑病变一样,严重的并发症
可以源于血管畸形和周围脑实质的影响。
最近,Sturge-Weber基金会(SWF)将患者和临床医生汇总到
确定对患者的未满足需求。而神经系统症状在内,包括癫痫发作和
头痛很常见,类似中风的情节,严重的癫痫发作和偏头痛头痛
被认为会显着影响患者的生活质量。用于防止这些的当前治疗
症状包括阿司匹林和癫痫药,但纵向都没有得到很好的支持
研究。也不清楚什么原因导致中风样症状或如何识别SWS患者
有这些症状的风险。优雅的连续大脑成像研究
提供了重要的线索,显示了血管结构本身的变化
围绕大脑实质,包括可能构成这些基础的大脑钙化
症状。因此,另一个潜在的令人兴奋的治疗方法是通过
重新利用药物。在这里,我们将通过
鉴定AT风险患者,当前治疗分析以及可靠的识别,
临床上有用和预测的生物标志物。
我们计划扩展患者注册表数据,以整合纵向临床,放射学和
患者的血液生物标志物以确定有严重神经症状的风险的风险
并确定潜在的治疗方法(目标1)。我们将确定会改变的成像生物标志物
随着时间的流逝,与严重的神经系统症状相关(AIM 2)。最后,对于入学的患者
谁出现严重的神经系统症状,将筛选血浆样本
基线,在严重症状期间和之后的炎症变化以识别预测性
临床试验的生物标志物(AIM 3)。主要的可交付方式将是临床上有用的,整合的
纵向数据库和仪表板工具,以帮助可视化数据,以帮助临床医生更好
了解SWS突变后疾病过程的进展。
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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JEFFREY A LOEB其他文献
JEFFREY A LOEB的其他文献
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{{ truncateString('JEFFREY A LOEB', 18)}}的其他基金
Integration and interoperability of complex data and tissues from the human brain
人脑复杂数据和组织的集成和互操作性
- 批准号:
10789107 - 财政年份:2023
- 资助金额:
$ 36.73万 - 项目类别:
Molecular and Cellular Basis of Spiking and Seizures in Neocortical Epilepsy
新皮质癫痫发作和癫痫发作的分子和细胞基础
- 批准号:
9973121 - 财政年份:2019
- 资助金额:
$ 36.73万 - 项目类别:
Molecular and Cellular Basis of Spiking and Seizures in Neocortical Epilepsy
新皮质癫痫发作和癫痫发作的分子和细胞基础
- 批准号:
10613487 - 财政年份:2019
- 资助金额:
$ 36.73万 - 项目类别:
Molecular and Cellular Basis of Spiking and Seizures in Neocortical Epilepsy
新皮质癫痫发作和癫痫发作的分子和细胞基础
- 批准号:
10376208 - 财政年份:2019
- 资助金额:
$ 36.73万 - 项目类别:
Molecular and Cellular Basis of Spiking and Seizures in Neocortical Epilepsy
新皮质癫痫发作和癫痫发作的分子和细胞基础
- 批准号:
9816309 - 财政年份:2019
- 资助金额:
$ 36.73万 - 项目类别:
Soluble Neuregulins in Neuromuscular and Peripheral Nerve Development
可溶性神经调节蛋白在神经肌肉和周围神经发育中的作用
- 批准号:
8220869 - 财政年份:2010
- 资助金额:
$ 36.73万 - 项目类别:
Soluble Neuregulins in Neuromuscular and Peripheral Nerve Development
可溶性神经调节蛋白在神经肌肉和周围神经发育中的作用
- 批准号:
8411137 - 财政年份:2010
- 资助金额:
$ 36.73万 - 项目类别:
Soluble Neuregulins in Neuromuscular and Peripheral Nerve Development
可溶性神经调节蛋白在神经肌肉和周围神经发育中的作用
- 批准号:
7786412 - 财政年份:2010
- 资助金额:
$ 36.73万 - 项目类别:
Soluble Neuregulins in Neuromuscular and Peripheral Nerve Development
可溶性神经调节蛋白在神经肌肉和周围神经发育中的作用
- 批准号:
8020025 - 财政年份:2010
- 资助金额:
$ 36.73万 - 项目类别:
Integrated Longitudinal Studies to Identify Biomarkers and Therapeutic Strategies for Sturge-Weber Syndrome
识别斯特奇-韦伯综合征生物标志物和治疗策略的综合纵向研究
- 批准号:
10212461 - 财政年份:2009
- 资助金额:
$ 36.73万 - 项目类别:
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