Assessment of Chemotherapy-Induced Peripheral Neuropathy Susceptibility Using Patient-derived iPSC Technology
使用患者来源的 iPSC 技术评估化疗引起的周围神经病变的易感性
基本信息
- 批准号:9450944
- 负责人:
- 金额:$ 36.37万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-09-18 至 2022-08-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdjuvantAdvanced Malignant NeoplasmAdverse effectsAfferent NeuronsAxonBiological AssayBiological ModelsBlindedCRISPR/Cas technologyCell LineCharcot-Marie-Tooth DiseaseChemotherapy-induced peripheral neuropathyClustered Regularly Interspaced Short Palindromic RepeatsCohort StudiesComplicationDefectDevelopmentDiseaseDistalDoseDose-LimitingEnrollmentFibroblastsFrequenciesFutureGene MutationGenesGenetic Predisposition to DiseaseGoalsHumanHuman BiologyIn VitroInheritedLeadMalignant NeoplasmsMethodologyMicrofluidicsModelingMorbidity - disease rateNeurologicNeuronsNumbnessOutcomePaclitaxelPainPathologicPatientsPeripheral Nervous System DiseasesPrecision therapeuticsPredispositionRegimenRisk FactorsRodentSamplingSeveritiesSkinSystemTechnologyTestingadult stem cellbasecancer therapychemotherapyclinical phenotypecohortdesignexperimental studygene correctiongenetic associationhealthy volunteerimmortalized cellindividual patientinduced pluripotent stem cellmalignant breast neoplasmneuronal cell bodyneuroprotectionneurotoxicneurotoxicityneurotoxicologynovelprecision medicinepredictive modelingprevent
项目摘要
PROJECT SUMMARY/ABSTRACT
Chemotherapy-induced peripheral neuropathy (CIPN) is a serious side effect that causes morbidity
and limits the dose of chemotherapy allowed to treat cancers. Of those receiving neurotoxic
chemotherapy, approximately 30-40% of patients develop CIPN, yet the risk factors for developing
this are poorly understood. The goal of this project is to test whether susceptibility to CIPN can be
predicted in vitro by employing our novel CIPN-in-a-dish neurotoxicology assay that uses iPSC-
derived sensory neuron from patient samples. In the first Specific Aim, sensory neurons (iSN) will
be derived from patients with Charcot-Marie-Tooth disease (hereditary peripheral neuropathy).
First, the CIPN-in-a-dish assay will be used to compare susceptibility between iSN from CMT
patients and healthy controls. Subsequently CMT samples will have their deleterious gene mutation
corrected using gene-editing technology (CRISPR/Cas) and CIPN susceptibility will be compared
between the pathologic iSN and gene-corrected iSN. In the second Specific Aim, iSN will be derived
from a cohort of patients with breast cancer that have received standard adjuvant paclitaxel
chemotherapy. Again using the CIPN-in-a-dish assay, iSN from patients that have clearly
developed CIPN from paclitaxel will be compared in a blinded fashion with patients that clearly
have not. These studies will serve two important functions: 1) they are a “proof-of-principle” study
that determines whether this approach using patient samples can be used to predict CIPN in
individual patients, 2) a hypothesis-generating study wherein patient samples will allow for
directed studies of mechanisms of CIPN susceptibility. The potential future application of this
technology will be to use a patient's own neurons to determine their susceptibility to the neurotoxic
effects of specific chemotherapy, thus allowing for personalized precision medicine for the patient
with cancer.
项目总结/摘要
化疗引起的周围神经病变(CIPN)是一种严重的副作用,导致发病率
并限制了治疗癌症的化疗剂量。在接受神经毒素的人中,
化疗后,约30-40%的患者发生CIPN,但发生CIPN的风险因素
人们对此知之甚少。该项目的目标是测试是否可以对CIPN的易感性进行评估。
通过使用我们的新型CIPN-在-皿神经毒理学测定法,使用iPSC-
从患者样本中提取感觉神经元。在第一个特定目标中,感觉神经元(iSN)将
来自Charcot-Marie-Tooth病(遗传性周围神经病)患者。
首先,将使用CIPN培养皿试验比较CMT的iSN之间的敏感性
患者和健康对照。随后CMT样本将有其有害的基因突变
将比较使用基因编辑技术(CRISPR/Cas)和CIPN敏感性进行校正
病理性iSN和基因校正iSN之间的差异。在第二个具体目标中,将导出iSN
从接受标准辅助紫杉醇的乳腺癌患者队列中
化疗再次使用CIPN-在-皿测定,iSN从患者,
将以盲法将紫杉醇引起的CIPN与明确
没有。这些研究将发挥两个重要作用:1)它们是一项“原理证明”研究
确定这种使用患者样本的方法是否可用于预测CIPN,
个体患者,2)假设生成研究,其中患者样品将允许
CIPN易感性机制的定向研究。未来的潜在应用
这项技术将利用病人自己的神经元来确定他们对神经毒素的敏感性,
特异性化疗的效果,从而为患者提供个性化的精准医疗
得了癌症
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 }}
Nathan P Staff其他文献
Nathan P Staff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('Nathan P Staff', 18)}}的其他基金
The Mayo Clinic NeuroNEXT Clinical Research Site
梅奥诊所 NeuroNEXT 临床研究网站
- 批准号:
10743328 - 财政年份:2023
- 资助金额:
$ 36.37万 - 项目类别:
PHLPP inhibition and Osteoarthritis-Associated Pain
PHLPP 抑制和骨关节炎相关疼痛
- 批准号:
10581073 - 财政年份:2023
- 资助金额:
$ 36.37万 - 项目类别:
Investigating the role of MAP2 in chemotherapy-induced peripheral neurotoxicity
研究 MAP2 在化疗引起的周围神经毒性中的作用
- 批准号:
10559108 - 财政年份:2023
- 资助金额:
$ 36.37万 - 项目类别:
Assessment of Chemotherapy-Induced Peripheral Neuropathy Susceptibility Using Patient-derived iPSC Technology
使用患者来源的 iPSC 技术评估化疗引起的周围神经病变的易感性
- 批准号:
9763518 - 财政年份:2017
- 资助金额:
$ 36.37万 - 项目类别:
Mechanisms of Bortezomib-induced Peripheral Neuropathy
硼替佐米诱发周围神经病变的机制
- 批准号:
9093719 - 财政年份:2012
- 资助金额:
$ 36.37万 - 项目类别:
Mechanisms of Bortezomib-induced Peripheral Neuropathy
硼替佐米诱发周围神经病变的机制
- 批准号:
8505004 - 财政年份:2012
- 资助金额:
$ 36.37万 - 项目类别:
Mechanisms of Bortezomib-induced Peripheral Neuropathy
硼替佐米诱发周围神经病变的机制
- 批准号:
8677584 - 财政年份:2012
- 资助金额:
$ 36.37万 - 项目类别:
Mechanisms of Bortezomib-induced Peripheral Neuropathy
硼替佐米诱发周围神经病变的机制
- 批准号:
8350911 - 财政年份:2012
- 资助金额:
$ 36.37万 - 项目类别:
Dopaminergic modulation of CA1 intrinsic excitability
CA1 内在兴奋性的多巴胺能调节
- 批准号:
6719028 - 财政年份:2002
- 资助金额:
$ 36.37万 - 项目类别:
Dopaminergic modulation of CA1 intrinsic excitability
CA1 内在兴奋性的多巴胺能调节
- 批准号:
6634372 - 财政年份:2002
- 资助金额:
$ 36.37万 - 项目类别:
相似海外基金
Metachronous synergistic effects of preoperative viral therapy and postoperative adjuvant immunotherapy via long-term antitumor immunity
术前病毒治疗和术后辅助免疫治疗通过长期抗肿瘤免疫产生异时协同效应
- 批准号:
23K08213 - 财政年份:2023
- 资助金额:
$ 36.37万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Improving the therapeutic immunity of cancer vaccine with multi-adjuvant polymeric nanoparticles
多佐剂聚合物纳米粒子提高癌症疫苗的治疗免疫力
- 批准号:
2881726 - 财政年份:2023
- 资助金额:
$ 36.37万 - 项目类别:
Studentship
Evaluation of the Sensitivity to Endocrine Therapy (SET ER/PR) Assay to predict benefit from extended duration of adjuvant endocrine therapy in the NSABP B-42 trial
NSABP B-42 试验中内分泌治疗敏感性 (SET ER/PR) 测定的评估,用于预测延长辅助内分泌治疗持续时间的益处
- 批准号:
10722146 - 财政年份:2023
- 资助金额:
$ 36.37万 - 项目类别:
Countering sympathetic vasoconstriction during skeletal muscle exercise as an adjuvant therapy for DMD
骨骼肌运动期间对抗交感血管收缩作为 DMD 的辅助治疗
- 批准号:
10735090 - 财政年份:2023
- 资助金额:
$ 36.37万 - 项目类别:
AUGMENTING THE QUALITY AND DURATION OF THE IMMUNE RESPONSE WITH A NOVEL TLR2 AGONIST-ALUMINUM COMBINATION ADJUVANT
使用新型 TLR2 激动剂-铝组合佐剂增强免疫反应的质量和持续时间
- 批准号:
10933287 - 财政年份:2023
- 资助金额:
$ 36.37万 - 项目类别:
DEVELOPMENT OF SAS A SYNTHETIC AS01-LIKE ADJUVANT SYSTEM FOR INFLUENZA VACCINES
流感疫苗类 AS01 合成佐剂系统 SAS 的开发
- 批准号:
10935776 - 财政年份:2023
- 资助金额:
$ 36.37万 - 项目类别:
DEVELOPMENT OF SMALL-MOLECULE DUAL ADJUVANT SYSTEM FOR INFLUENZA VIRUS VACCINE
流感病毒疫苗小分子双佐剂体系的研制
- 批准号:
10935796 - 财政年份:2023
- 资助金额:
$ 36.37万 - 项目类别:
A GLYCOLIPID ADJUVANT 7DW8-5 FOR MALARIA VACCINES
用于疟疾疫苗的糖脂佐剂 7DW8-5
- 批准号:
10935775 - 财政年份:2023
- 资助金额:
$ 36.37万 - 项目类别:
Adjuvant strategies for universal and multiseasonal influenza vaccine candidates in the context of pre-existing immunity
在已有免疫力的情况下通用和多季节流感候选疫苗的辅助策略
- 批准号:
10649041 - 财政年份:2023
- 资助金额:
$ 36.37万 - 项目类别:
Adjuvant Photodynamic Therapy to Reduce Bacterial Bioburden in High-Energy Contaminated Open Fractures
辅助光动力疗法可减少高能污染开放性骨折中的细菌生物负载
- 批准号:
10735964 - 财政年份:2023
- 资助金额:
$ 36.37万 - 项目类别: