A theranostic system for ultrasound-facilitated blood-brain barrier opening
A theranostic system for ultrasound-facilitated blood-brain barrier opening
批准号:
10318649
负责人:
Elisa E. Konofagou
金额:
$63.14万
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
已结题
起止时间:
2020-03-01 至 2023-12-31
关键词:
3-DimensionalAdoptionAffectAgeAgingAmericanAmplifiersAreaBehavioralBehavioral SymptomsBlood - brain barrier anatomyBrain imagingCentral Nervous System DiseasesClinicClinicalCognitiveDiagnosticDiagnostic ImagingDiffuseDiseaseDrug Delivery SystemsEarly treatmentElementsEngineeringFDA approvedFeasibility StudiesFluorescenceFocused UltrasoundGene DeliveryHumanImageLinkMagnetic Resonance ImagingMapsMechanicsMediatingMethodologyMicrobubblesModelingMovement DisordersMusNeurodegenerative DisordersNeuronavigationNeurosciencesOutcomeParkinson DiseasePathway interactionsPatientsPermeabilityPersonsPharmaceutical PreparationsPharmacologyPhysiologic pulsePositron-Emission TomographyPrimate DiseasesPrimatesRiskSafetySystemTechniquesTestingTherapeutic UsesTimeTransducersTreatment EfficacyUltrasonographybehavior testbrain parenchymacohortcraniumdelivery vehicledesigndopaminergic neurondosageeffective therapyefficacy evaluationfallshuman old age (65+)in vivoindexingmedical specialtiesmodel developmentmotor controlmotor symptommouse modelmultidisciplinaryneuroprotectionneurorestorationnigrostriatal pathwaynonhuman primateparkinsonian modelparkinsonian non-human primateparkinsonian rodentpressurereal time monitoringrestorationsafety assessmentsafety studysmall moleculesuccesstheranosticsultrasound
中文摘要
今天,超过3500万美国人年龄在65岁以上。在接下来的30年里,这个数字是
很可能翻一番,使越来越多的人面临神经退行性疾病的风险增加。
在过去的几十年里,无数的小分子和大分子产品被
为治疗神经退行性疾病而开发,效果参差不齐。当给药时
在体内,血脑屏障(BBB)阻止它们向受影响的区域输送
那些疾病。BBB的安全和局部开放已被证明构成了同样的
这是一个巨大的挑战。聚焦超声(FUS),结合微泡,仍然是
可以无创地诱导局部血脑屏障开放的唯一技术。此前,我们小组已经
证明了脑内多巴胺能神经元的神经保护和神经修复作用
超声可诱导疾病早期的黑质纹状体通路
药物递送。在这项研究中,我们将开发和优化一种治疗超声系统,它可以
同时在体内诱导和定位小鼠和灵长类动物的血脑屏障开放。作为次要角色
目的,我们将确定这种新的血脑屏障开放系统是否足以诱发血脑屏障
通过基因传递诱导小鼠神经保护和神经修复的足够水平
和NHP用于治疗早期帕金森病模型的运动症状。
警局阶段。组建的多学科团队涵盖了所有关键的专业领域,如
如超声波和微泡工程、神经科学以及核磁共振、正电子发射计算机断层扫描和荧光
脑成像、行为测试和小鼠模型开发以及临床特长
运动障碍。因此,这项研究将确定鼻咽部是否可以有更多的
通过在诊断成像扫描仪中实施而产生的广泛影响和足够有效
用于早期帕金森氏症的治疗,并结合基因输送。
英文摘要
Today, over 35 million Americans are over the age of 65. Within the next 30 years this number is
likely to double, putting more and more people at increased risk of neurodegenerative disease.
Over the past several decades, numerous small- and large-molecule products have been
developed for treatment of neurodegenerative diseases with mixed success. When administered
systemically in vivo, the blood-brain barrier (BBB) inhibits their delivery to the regions affected by
those diseases. Safe and localized opening of the BBB has been proven to pose an equally
significant challenge. Focused Ultrasound (FUS), in conjunction with microbubbles, remains the
sole technique that can induce localized BBB opening noninvasively. Previously, our group has
demonstrated that neuroprotection and neurorestoration in the dopaminergic neurons in the
nigrostriatal pathway at the early stages of disease can be induced through ultrasound-mediated
drug delivery. In this study, we will develop and optimize a theranostic ultrasound system that can
simultaneously induce and map the BBB opening in mice and primates in vivo. As a secondary
objective, we will determine whether this new BBB opening systems are sufficient to induce BBB
at sufficient levels to induce neuroprotection and neurorestoration through gene delivery in mice
and NHP for the treatment of motor symptoms in Parkinsonian models associated with early-
stage PD. The multi-disciplinary team assembled encompasses all critical specialty areas such
as ultrasound and microbubble engineering, neuroscience as well as MRI, PET and fluorescence
brain imaging, behavioral testing and mouse model development as well as clinical specialty in
movement disorders.This study will thus determine whether theranostic FUS can have a more
widespread impact by being implemented in diagnostic imaging scanners and efficacious enough
for the treatment of early stage Parkinson’s in conjunction with gene delivery.
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