Proteomics of human vitreous to investigate mechanisms underlying the variability in anti-VEGF treatment response in neovascular AMD patients
人玻璃体蛋白质组学研究新生血管性 AMD 患者抗 VEGF 治疗反应差异的机制
基本信息
- 批准号:10673722
- 负责人:
- 金额:$ 17.5万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-01 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAftercareAgeAge related macular degenerationAlternative TherapiesAngiogenic ProteinsAvastinBlindnessClassificationClinicalClinical DataCombined Modality TherapyConsensusDataDevelopmentDiseaseDisease ProgressionDoseElderlyExudative age-related macular degenerationFundusGuidelinesHumanImmunoassayInflammationInflammatoryInjectionsKnowledgeLogistic RegressionsMeasurementMeasuresMolecularOpticsOutcomePathogenesisPathway interactionsPatientsProteinsProteomicsResourcesRetinal DiseasesSamplingTechnologyTestingTimeTomogramTreatment EfficacyTreatment FactorVariantVascular Endothelial Growth FactorsVisionVisual Acuityangiogenesisbevacizumabblindcohorteffective therapyinnovationinsightneovascularnovelpersonalized medicinepreservationprotein foldingprotein functionrepositoryresponsesexstandard of caretherapeutic targettreatment responsetreatment strategytrendvisual optics
项目摘要
PROJECT SUMMARY
Age-related macular degeneration (AMD) is the leading cause of severe, irreversible vision loss in older
adults worldwide. Most vision loss in AMD is caused by the advanced neovascular form of the disease
(NVAMD). Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections are effective in preserving
vision for many patients, but there is marked variability among NVAMD patients in treatment response.
Molecular factors contributing to this variability in anti-VEGF response represent a critical gap in knowledge.
Our proposal addresses this knowledge gap directly by leveraging a unique and powerful resource. We
have an exclusive repository of deidentified vitreous samples collected in-office from more than 1,100 patients
treated for retinal diseases, including many with NVAMD. We will couple this resource with a highly sensitive,
high-throughput multiplex immunoassay-based proteomics technology to identify vitreous proteins associated
with anti-VEGF treatment response in NVAMD. We hypothesize that variation in vitreous levels of inflammatory
and angiogenic proteins impacts the fundamental mechanisms that underlie the variability in response to anti-
VEGF treatment. To test this hypothesis, we will measure levels of proteins involved in inflammation and
angiogenesis in vitreous samples collected from NVAMD patients both prior to and throughout the course of
treatment. We have identified a cohort of 83 treatment-naïve NVAMD patients who received the standard three
monthly loading doses of intravitreal bevacizumab, followed by monthly injections as needed based on visual
acuity, fundus examination, and OCT assessment. Using visual acuity and OCT measurements, each patient’s
primary (one month after three loading doses; Month 3) and secondary (6 months after treatment initiation;
Month 6) anti-VEGF treatment responses were classified as Good, Partial, Poor, or Non-Response.
In Aim 1, we will use Olink Proteomics’ multiplex immunoassays to measure levels of 733 proteins involved
in inflammation and angiogenesis in vitreous samples collected from these NVAMD patients prior to their initial
bevacizumab injection. To compare between Good+Partial Responders and Poor+Non-Responders, we will
perform logistic regression of responder status (Good/Partial or Poor/Non-Response) against baseline levels of
each protein with and without adjustment for covariates at both primary and secondary response timepoints.
In Aim 2, we will determine the longitudinal bevacizumab-induced changes in vitreous levels of
inflammatory and angiogenic proteins that correlate with clinical outcomes in NVAMD patients. For 58 of the
patients from Aim 1, we have additional vitreous samples collected at Month 1 (one month after treatment
initiation), Month 3, and Month 6. We will quantify levels of the same 733 inflammatory and angiogenic proteins
in these longitudinal vitreous samples. We will compare the protein fold-changes and the trend of protein
changes over time between Good/Partial Responders and Poor/Non-Responders at each response timepoint.
项目总结
老年性黄斑变性(AMD)是导致老年人严重、不可逆性视力丧失的主要原因
世界各地的成年人。AMD的大部分视力丧失是由晚期新生血管疾病引起的
(NVAMD)。玻璃体内注射抗血管内皮生长因子(抗血管内皮生长因子)有效地保存了
对许多患者的视力有影响,但NVAMD患者的治疗反应存在显著差异。
导致抗血管内皮生长因子反应的这种差异性的分子因素是知识上的一个关键差距。
我们的建议通过利用一种独特而强大的资源直接解决了这一知识差距。我们
拥有从1100多名患者的办公室内收集的已确认玻璃体样本的独家存储库
治疗视网膜疾病,包括许多患有NVAMD的人。我们将把这一资源与高度敏感的
基于高通量多重免疫分析的蛋白质组学技术鉴定玻璃体相关蛋白
抗血管内皮细胞生长因子治疗NVAMD有效。我们假设玻璃体炎症水平的变化
而血管生成蛋白影响的基本机制是基础的可变性的反应
血管内皮生长因子治疗。为了验证这一假设,我们将测量参与炎症和
NVAMD患者治疗前和治疗过程中玻璃体标本中的血管生成
治疗。我们已经确定了83名接受标准3种治疗的单纯NVAMD患者的队列
每月玻璃体内注射贝伐单抗,然后根据视力需要每月注射
视力、眼底检查和OCT评估。使用视力和OCT测量,每个患者的
初级(三次负荷量后1个月;第3个月)和继发性(开始治疗后6个月;
6个月)抗血管内皮生长因子治疗反应分为良好、部分、差或无反应。
在目标1中,我们将使用Olink蛋白质组学的多重免疫分析来测量涉及的733个蛋白质的水平
NVAMD患者玻璃体标本中炎症和血管生成的变化
贝伐单抗注射剂。为了比较良好+部分响应者和较差+非响应者,我们将
根据以下基准水平对应答者状态(良好/部分或差/无反应)进行逻辑回归
每个蛋白质在第一和第二响应时间点都有和没有对协变量进行调整。
在目标2中,我们将确定贝伐单抗引起的玻璃体水平的纵向变化
炎症和血管生成蛋白与NVAMD患者的临床结局相关。对于其中的58个
来自AIM 1的患者,我们在1个月(治疗后1个月)收集了额外的玻璃体样本
开始)、3个月和6个月。我们将量化相同的733个炎症和血管生成蛋白的水平
在这些纵向的玻璃样本中。我们将比较蛋白质的折叠变化和蛋白质的趋势
在每个响应时间点,良好/部分响应者和较差/无响应者之间的时间变化。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Milam A Brantley其他文献
Milam A Brantley的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Milam A Brantley', 18)}}的其他基金
Proteomics of human vitreous to investigate mechanisms underlying the variability in anti-VEGF treatment response in neovascular AMD patients
人玻璃体蛋白质组学研究新生血管性 AMD 患者抗 VEGF 治疗反应差异的机制
- 批准号:
10507176 - 财政年份:2022
- 资助金额:
$ 17.5万 - 项目类别:
Metabolomic and Genetic Interactions in Age-Related Macular Degeneration
年龄相关性黄斑变性的代谢组学和遗传相互作用
- 批准号:
8576080 - 财政年份:2013
- 资助金额:
$ 17.5万 - 项目类别:
Metabolomic and Genetic Interactions in Age-Related Macular Degeneration
年龄相关性黄斑变性的代谢组学和遗传相互作用
- 批准号:
8717668 - 财政年份:2013
- 资助金额:
$ 17.5万 - 项目类别:
Metabolomic and Genetic Interactions in Age-Related Macular Degeneration
年龄相关性黄斑变性的代谢组学和遗传相互作用
- 批准号:
9302786 - 财政年份:2013
- 资助金额:
$ 17.5万 - 项目类别:
Role of GDNF Family Ligands in Photoreceptor Rescue
GDNF 家族配体在光感受器救援中的作用
- 批准号:
7364163 - 财政年份:2005
- 资助金额:
$ 17.5万 - 项目类别:
Role of GDNF Family Ligands in Photoreceptor Rescue
GDNF 家族配体在光感受器救援中的作用
- 批准号:
6858852 - 财政年份:2005
- 资助金额:
$ 17.5万 - 项目类别:
相似海外基金
Life outside institutions: histories of mental health aftercare 1900 - 1960
机构外的生活:1900 - 1960 年心理健康善后护理的历史
- 批准号:
DP240100640 - 财政年份:2024
- 资助金额:
$ 17.5万 - 项目类别:
Discovery Projects
Development of a program to promote psychological independence support in the aftercare of children's homes
制定一项计划,促进儿童之家善后护理中的心理独立支持
- 批准号:
23K01889 - 财政年份:2023
- 资助金额:
$ 17.5万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Integrating Smoking Cessation in Tattoo Aftercare
将戒烟融入纹身后护理中
- 批准号:
10452217 - 财政年份:2022
- 资助金额:
$ 17.5万 - 项目类别:
Integrating Smoking Cessation in Tattoo Aftercare
将戒烟融入纹身后护理中
- 批准号:
10670838 - 财政年份:2022
- 资助金额:
$ 17.5万 - 项目类别:
Aftercare for young people: A sociological study of resource opportunities
年轻人的善后护理:资源机会的社会学研究
- 批准号:
DP200100492 - 财政年份:2020
- 资助金额:
$ 17.5万 - 项目类别:
Discovery Projects
Creating a National Aftercare Strategy for Survivors of Pediatric Cancer
为小儿癌症幸存者制定国家善后护理策略
- 批准号:
407264 - 财政年份:2019
- 资助金额:
$ 17.5万 - 项目类别:
Operating Grants
Aftercare of green infrastructure: creating algorithm for resolving human-bird conflicts
绿色基础设施的善后工作:创建解决人鸟冲突的算法
- 批准号:
18K18240 - 财政年份:2018
- 资助金额:
$ 17.5万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Development of an aftercare model for children who have experienced invasive procedures
为经历过侵入性手术的儿童开发善后护理模型
- 批准号:
17K12379 - 财政年份:2017
- 资助金额:
$ 17.5万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Development of a Comprehensive Aftercare Program for children's self-reliance support facility
为儿童自力更生支持设施制定综合善后护理计划
- 批准号:
17K13937 - 财政年份:2017
- 资助金额:
$ 17.5万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Project#2 Extending Treatment Effects Through an Adaptive Aftercare Intervention
项目
- 批准号:
8742767 - 财政年份:2014
- 资助金额:
$ 17.5万 - 项目类别: