Methods of improving neurodegenerative disorders by targeted delivery of therapeutic agents

Inventors

Rezai, Ali R. • Finomore, Jr., Victor • Amireskandari, Annahita • Haut, Marc

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 relates to methods of improving a neurodegenerative disorder in a human patient suffering therefrom. The method includes determining a target site of the human patient's brain that is affected by the neurodegenerative disorder, based on biomarkers of neurodegenerative/cognitive disorders such as beta-amyloid protein and tau protein, and other described biomarkers such as alpha-synuclein and neurofilament light chain (NFL).

After the target site is determined, the invention provides therapy that applies focused ultrasound (FUS) sonication via an ultrasound delivery device to the target site. The FUS sonication is applied based on at least one feedback parameter comprising an optical parameter, including imaging parameter changes, microbubble cavitation/vibration analysis, and optical parameters derived from retina/optic nerve imaging such as optical coherence tomography (OCT), OCT angiography, and fundus photography.

The method also introduces a therapeutic agent to the target site before, during, or after application of the FUS sonication. The therapeutic agent includes anti-amyloid antibodies such as aducanumab and lecanemab, and the content describes feedback-based assessment of blood-brain barrier (BBB) opening and adjustable treatment based on feedback, including assessment and analysis related to microbubbles and microbubble administration with imaging guidance.

Claims Coverage

The partial content identifies one independent claim (clm-00001). The independent claim includes three principal inventive elements: target-site determination, feedback-based focused ultrasound sonication using an optical-parameter feedback, and timing-controlled introduction of a therapeutic agent relative to the ultrasound sonication.

Across the identified independent claim, the coverage centers on using a determined brain target site in a human patient with a neurodegenerative disorder, applying FUS sonication based on at least one feedback parameter that comprises an optical parameter, and introducing a therapeutic agent at the target site with specified timing relative to the FUS sonication.

Stated Advantages

Documented Applications