Methods of improving neurodegenerative disorders by targeted delivery of therapeutic agents
Inventors
Rezai, Ali R. • Finomore, Jr., Victor • Carpenter, Jeff • Haut, Marc
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Assignees
MemberWest Virginia UniversityWest Virginia UniversityWest Virginia University is a public R1 research institution offering diverse undergraduate and graduate programs across science, engineering, business, creative arts, and media. The university emphasizes experiential learning, research, and innovation, with notable strengths in academic program development, research excellence, community engagement, and a commitment to affordability, career readiness, and student success. WVU supports a vibrant campus environment, industry partnerships, and impactful scholarship, preparing students for careers through hands-on education, research, and applied learning.
West Virginia University is a public R1 research institution offering diverse undergraduate and graduate programs across science, engineering, business, creative arts, and media. The university emphasizes experiential learning, research, and innovation, with notable strengths in academic program development, research excellence, community engagement, and a commitment to affordability, career readiness, and student success. WVU supports a vibrant campus environment, industry partnerships, and impactful scholarship, preparing students for careers through hands-on education, research, and applied learning.
Publication Number
US-12467932-B2
Publication Date
2025-11-11
Expiration Date
Abstract
A method of improving a neurodegenerative or cognitive disorder in a human patient suffering therefrom is provided by determining a target site of the human patient's brain that is affected by the neurodegenerative disorder or cognitive disorder and providing a therapy to the human patient. The therapy includes applying a low intensity focused ultrasound (LiFUS) sonication via an ultrasound delivery device to the target site based on an imaging parameter, a microbubble cavitation; an optical parameter, a bodily fluid parameter, or a physiological or anatomical parameter of the human patient's brain. A therapeutic agent is introduced to the target site before, after or during application of the LiFUS sonication.
Core Innovation
The invention provides methods to improve a neurodegenerative disorder in a human patient suffering therefrom by applying focused ultrasound (FUS) sonication to a determined target site of the human patient's brain. The therapy includes introducing a therapeutic agent to the target site before, during, or after application of the FUS sonication. The approach is guided by at least one feedback parameter used to base the FUS sonication on monitoring signals during therapy.
The feedback parameters include at least one or more of an imaging parameter, an acoustic microbubble vibration analysis, an optical parameter, a bodily fluid parameter, or a physiological or anatomical parameter. Imaging parameter guidance includes PET and MRI sequences, including GRE T2*, T1 contrast, T2 FLAIR, and SWI, and the document describes workflows that use merged PET/MRI scans to guide targeting and therapy decisions.
The method further includes feedback based on acoustic microbubble vibration analysis, optical measures related to retina/optic nerve, and bodily-fluid biomarker assessment. Biomarkers include beta-amyloid protein and tau protein measured from bodily fluids such as urine, blood, or CSF and/or from tissue, and the document describes determining clinical candidate determination and likelihood of developing a neurodegenerative disorder to support prophylactic/mitigation based on biomarker detection and guided therapy.
Claims Coverage
Independent claim clm-00001 covers a method framework that combines brain target determination, FUS sonication based on feedback parameters with one or more specified parameter types, and delivery of a therapeutic agent before, during, or after sonication. The dependent claims refine the feedback parameter inputs by specifying particular imaging modalities and by adding signal-change decision rules for selected imaging signals and biomarker-driven therapy adjustment.
Target site determination and agent-timed FUS therapy guided by feedback
A method of improving a neurodegenerative disorder comprising determining a target site of a human patient's brain affected by the neurodegenerative disorder; applying focused ultrasound sonication to the target site via an ultrasound delivery device based on at least one feedback parameter comprising at least one or more of an imaging parameter, an acoustic microbubble vibration analysis, an optical parameter, a bodily fluid parameter, or a physiological or anatomical parameter; and introducing a therapeutic agent to the target site before, during, or after application of the FUS sonication.
Feedback based on acoustic microbubble vibration analysis
The method in which the at least one feedback parameter comprises acoustic microbubble vibration analysis.
Imaging parameter includes PET and MRI sequences
The method in which the imaging parameters include one or more of performing one or more imaging types on a human patient's brain including PET and MRI sequences including GRE T2*, T1 contrast, T2 FLAIR, and SWI.
Therapy decision using T2 weighted FLAIR signal change relative to threshold or prior scan
The method further including determining whether a T2 weighted FLAIR signal increases or decreases relative to a threshold value or relative to a pre-therapy T2 weighted FLAIR scan, and delivering or adjusting therapy accordingly.
Therapy decision using SWI signal change relative to threshold or prior scan
The method further including determining whether an SWI signal increases or decreases relative to a threshold value or relative to a prior SWI scan before therapy, and delivering or adjusting therapy based on that increase or decrease.
Therapy adjustment using beta-amyloid and tau biomarker changes in bodily fluids or tissue
The method further including determining changes in concentrations of beta-amyloid and tau and/or identifying a biomarker for a neurodegenerative disorder in urine, blood, CSF, or other bodily fluid or tissue, and delivering or adjusting therapy based on those changes or on biomarker presence.
Overall claim coverage centers on improving neurodegenerative disorders by delivering a therapeutic agent in temporal coordination with FUS sonication targeted to a brain site. The inventive features emphasize feedback-guided FUS based on one or more feedback parameter types, including specific imaging modalities, microbubble vibration analysis, and biomarker-driven therapy adjustment with decision rules using imaging signal changes and beta-amyloid/tau measurements.
Stated Advantages
Documented Applications
No documented applications found
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