Compositions and methods of detecting and treating alzheimer's disease

Abstract

Abstract The invention provides microbubbles and / or nanodroplets labeled with diagnostic and / or therapeutic ligands that are useful in the detection and treatment of Alzheimer’s disease, or related diseases and conditions, as well as methods of preparation and use thereof. Abstract The invention provides microbubbles and / or nanodroplets labeled with diagnostic and / or therapeutic ligands that are useful in the detection and treatment of Alzheimer's disease, or related diseases and conditions, as well as methods of preparation and use thereof. 20 24 20 51 63 29 J ul 2 02 4 A b s t r a c t 2 0 2 4 2 0 5 1 6 3 2 9 J u l 2 0 2 4

Description

Incorporation by Reference

[0093] References and citations to other documents, such as patents, patent applications, patent publications, journals, books, papers, web contents, have been made in this disclosure. All such documents are hereby incorporated herein by reference in their entirety for all purposes. Any material, or portion thereof, that is said to be incorporated by reference herein, but which conflicts with existing definitions, statements, or other disclosure material explicitly set forth herein is only incorporated to the extent that no conflict arises between that incorporated material and the present disclosure material. In the event of a conflict, the conflict is to be resolved in favor of the present disclosure as the preferred disclosure. Equivalents

[0094] The representative examples are intended to help illustrate the invention, and are not intended to, nor should they be construed to, limit the scope of the invention. Indeed, various modifications of the invention and many further embodiments thereof, in addition to those shown and described herein, will become apparent to those skilled in the art from the hill contents of this document, including the examples and the references to the scientific and patent literature included herein. The examples contain important additional information, exemplification and guidance that can be adapted to the practice of this invention in its various embodiments and equivalents thereof.

Claims

1. A microscopic or nanoscopic bubble / droplet conjugated thereto one or more enzyme or an antibody, or a fragment thereof, capable of degrading or otherwise metabolizing betaamyloid and / or tau protein.

2. The microscopic or nanoscopic bubble / droplet of claim 1, wherein each microscopic or nanoscopic bubble / droplet is conjugated to a plurality of the enzyme or an antibody, or a fragment thereof.

3. The microscopic or nanoscopic bubble / droplet of claim 1 or 2, wherein the enzyme or antibody is selected from insulin-degrading enzyme (IDE), neprilysin (NEP), endothelin-converting enzyme (ECE), angiotensin converting enzyme (ACE), plasmin, matrix metalloprotenases (MMPs), phosphatases, alkaline phosphatases (AP), and antibodies to amyloid beta, or a fragment thereof.

4. The microscopic or nanoscopic bubble / droplet of any one of claims 1-3, wherein the one or more enzyme or an antibody, or a fragment thereof, are conjugated to the microscopic or nanoscopic bubble / droplet via a PEG linker.

5. The microscopic or nanoscopic bubble / droplet of any one of claims 1-4, wherein the microscopic or nanoscopic bubble / droplet is fdled with a gaseous material.

6. The microscopic or nanoscopic bubble / droplet of claim 5, wherein the gaseous material comprises a fluorinated gas.

7. The microscopic or nanoscopic bubble / droplet of claim 6, wherein the fluorinated gas is selected from perfluoromethane, perfluoroethane, perfluoropropane, perfluorocyclopropane, perfluorobutane, perfluorocyclobutane, perfluoropentane,2024205163   29 Jul 2024perfluorocylcopentane, perfluorohexane, perfluorocyclohexane, and mixtures of two or more thereof.

8. The microscopic or nanoscopic bubble of claim 7, wherein the fluorinated gas is selected from perfluoropropane, perfluorocyclopropane, perfluorobutane, perfluorocyclobutane, perfluoropentane, perfluorocylcopentane, and mixtures of two or more thereof.

9. The microscopic or nanoscopic bubble / droplet of any of claims 1-8, being coated by a film-forming material.

10. The microscopic or nanoscopic bubble / droplet of claim 9, wherein the film-forming material comprises one or more lipids.

11. The microscopic or nanoscopic bubble / droplet of claim 10, wherein the lipids comprise a phospholipid or a mixture of phospholipids.

12. The microscopic or nanoscopic bubble / droplet of any one of claims 1-11, having a microscopic size ranging from about 0.5 to about 10 microns.

13. The microscopic or nanoscopic bubble / droplet of any one of claims 1-11, having a nanoscopic size ranging from about 120 nm to about 280 nm.

14. An aqueous emulsion or suspension comprising a microscopic bubble and / or nanoscopic droplet of any of claims 1-13.

15. The emulsion or suspension of claim 14, being in a homogenized form.

16. A method for treating Alzheimer’s disease, comprising:administering to a subject in need thereof an aqueous emulsion or suspension comprising a microscopic bubble and / or nanoscopic droplet of any of claims 1-13; and applying ultrasound to a targeted region of the brain of the subject.2024205163   29 Jul 202417. A film-forming material comprises one or more lipids, conjugated thereto one or more enzyme or an antibody, or a fragment thereof, capable of degrading or otherwise metabolizing beta-amyloid and / or tau protein.

18. A film-forming material of claim 17, wherein the enzyme or antibody is selected from insulin-degrading enzyme (IDE), neprilysin (NEP), endothelin-converting enzyme (ECE), angiotensin converting enzyme (ACE), plasmin, matrix metalloprotenases (MMPs), phosphatases, alkaline phosphatases (AP), and antibodies to amyloid beta, or a fragment thereof.

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