A theranostic system for ultrasound-facilitated blood-brain barrier opening

超声促进血脑屏障开放的治疗诊断系统

• 批准号: 9917485
• 负责人: Elisa E. Konofagou
• 金额: $ 69.06万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9917485
• 关键词: 3-Dimensional; Adoption; Affect; Age; Aging; American; Amplifiers; Area; Behavioral; Behavioral Symptoms; Blood - brain barrier anatomy; Brain imaging; Central Nervous System Diseases; Clinic; Clinical; Cognitive; Diagnostic; Diagnostic Imaging; Diffuse; Disease; Drug Delivery Systems; Early treatment; Elements; Engineering; FDA approved; Feasibility Studies; Fluorescence; Focused Ultrasound; Gene Delivery; Human; Image; Link; Magnetic Resonance Imaging; Maps; Mechanics; Mediating; Methodology; Microbubbles; Modeling; Monkeys; Movement Disorders; Mus; Neurodegenerative Disorders; Neuronavigation; Neurosciences; Outcome; Parkinson Disease; Parkinsonian Disorders; Pathway interactions; Patients; Permeability; Pharmaceutical Preparations; Pharmacology; Physiologic pulse; Positron-Emission Tomography; Primate Diseases; Primates; Risk; Safety; System; Techniques; Testing; Therapeutic Uses; Time; Transducers; Treatment Efficacy; Ultrasonography; behavior test; brain parenchyma; cohort; cranium; design; dopaminergic neuron; dosage; effective therapy; falls; human old age (65+); in vivo; indexing; medical specialties; model development; motor control; motor symptom; mouse model; multidisciplinary; neuroprotection; neurorestoration; nigrostriatal pathway; nonhuman primate; pressure; real time monitoring; restoration; safety study; small molecule; success; theranostics; vector

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.

今天，超过3500万美国人年龄超过65岁。在接下来的30年里，这个数字