Methods of treating or preventing alzheimer's disease and associated conditions

Patent metadata

Field	Value
Publication number	US-11058720-B2
Application number	US-201716303053-A
Country	US
Kind code	B2
Filing date	May 22, 2017
Priority date	May 20, 2016
Publication date	Jul 13, 2021
Grant date	Jul 13, 2021

Abstract

The present invention describes a method of treating, preventing, reducing the likelihood of or alleviating a symptom of Alzheimer's disease and associated conditions by increasing OPN expression. The invention further provides for a method of improving cognitive function in a subject in need thereof.

First claim

What is claimed is:

1. A method of treating Alzheimer's disease in a subject in need thereof comprising:
stimulating a population of innate immune cells ex vivo with glatiramer acetate to increase expression of osteopontin;
detecting the increased expression of osteopontin in said cells; and
administering to the subject a therapeutically effective amount of the population of innate immune cells that have been stimulated ex vivo with glatiramer acetate.

2. The method of claim 1 , wherein the innate immune cells comprise monocytes, macrophages, or combinations thereof.

3. The method of claim 2 , wherein the monocytes comprise bone marrow-derived monocytes, spleen-derived monocytes, CD115 positive monocytes (CD115 + monocytes), infiltrating monocytes, or combinations thereof.

4. The method of claim 1 , further comprising administering glatiramer acetate to the subject.

5. The method of claim 1 , wherein the administering comprises adoptive cell transfer, bone marrow transplantation, or direct delivery to the subject.

6. The method of claim 1 , wherein the treating of Alzheimer's disease comprises alleviating a symptom of Alzheimer's disease selected from the group consisting of memory loss, decline in non-memory aspects of cognition, impaired reasoning or judgment, behavior changes, impaired ability to carry out multistep tasks, hallucinations, delusions, paranoia and combinations thereof.

7. The method of claim 1 , wherein the administering results in an increase in MMP-9 in the subject, as measured by an immunoassay.

8. The method of claim 7 , wherein the administering results in decreased levels of a misfolded protein in the subject, as measured by an immunoassay.

9. The method of claim 8 , wherein the misfolded protein is amyloid beta (Aβ).

10. The method of claim 9 , wherein the Aβ is Aβ 40 and/or Aβ 42 .

11. The method of claim 7 , wherein treating Alzheimer's disease comprises enhancing clearance of pathological amyloid-β forms, as measured by an immunoassay.

12. The method of claim 7 , wherein treating Alzheimer's disease comprises rescuing synaptic structure, as measured by an immunoassay or microscope analysis.

13. A method of improving cognitive function in a subject in need thereof, comprising:
stimulating a population of innate immune cells ex vivo with glatiramer acetate to increase expression of osteopontin;
detecting the increased expression of osteopontin in said cells; and
administering to the subject a therapeutically effective amount of a composition comprising a the population of innate immune cells that have been stimulated ex vivo with glatiramer acetate.

14. The method of claim 13 , wherein the innate immune cells comprise monocytes, macrophages, or combinations thereof.

15. The method of claim 14 , wherein the monocytes comprise bone marrow-derived monocytes, spleen-derived monocytes, CD115 positive monocytes (C115+ monocytes), infiltrating monocytes, or combinations thereof.

16. The method of claim 13 , wherein the innate immune cells are phagocytic.

17. The method of claim 13 , further comprising administering glatiramer acetate to the subject.

18. The method of claim 13 , wherein the administering comprises adoptive cell transfer, bone marrow transplantation, or direct delivery to the subject.

19. The method of claim 13 , wherein the administering results in an increase in MMP-9 in the subject, as measured by an immunoassay.

20. The method of claim 13 , wherein the administering results in decreased levels of a misfolded protein in the subject, decreased inflammation in the subject, increased synaptic regeneration in the subject, recruitment of macrophages to an amyloid beta (Aβ) plaque site in the subject, or combinations thereof, as measured by an immunoassay or microscope analysis.

21. The method of claim 20 , wherein the misfolded protein is Aβ.

22. The method of claim 21 , wherein the Aβ is Aβ 40 and/or Aβ 42 .

Assignees

• Cedars Sinai Medical Center

Inventors

• Koronyo Maya
• Rentsendorj Altanchimeg
• Koronyo Yosef
• Black Keith

Classifications

• A61K40/416

  Antigens related to auto-immune diseases; Preparations to induce self-tolerance · CPC title

• A61K40/24

  Antigen-presenting cells [APC] · CPC title

• A61K40/22

  Immunosuppressive or immunotolerising · CPC title

• A61K40/17

  Monocytes; Macrophages · CPC title

• A61K2239/31

  characterized by the route of administration · CPC title