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

Patent metadata

Field	Value
Publication number	US-2019290687-A1
Application number	US-201716303053-A
Country	US
Kind code	A1
Filing date	May 22, 2017
Priority date	May 20, 2016
Publication date	Sep 26, 2019
Grant date	—

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, preventing or reducing the likelihood of Alzheimer's disease, alleviating a symptom of Alzheimer's disease, rescuing synaptic structure and/or cognitive function, enhancing the clearance of pathological amyloid-β forms or inhibiting the decline of neuronal structure and function in a subject in need thereof comprising:
providing a composition that, when administered to the subject, results in increased levels of osteopontin (OPN) relative to a normal subject; and
administering an amount of the composition to the subject sufficient to increase said levels of OPN.

2 . The method of claim 1 , wherein the composition comprises OPN expressing innate immune cells, recombinant OPN, OPN fragments, OPN derivatives, OPN mimetics, OPN analogues or a combination thereof.

3 . The method of claim 1 , wherein the composition stimulates expression of OPN in innate immune cells.

4 . The method of claim 3 , wherein the innate immune cells comprise monocytes, macrophages or combinations thereof.

5 . The method of claim 4 , wherein the monocytes comprise bone marrow-derived monocytes, spleen-derived monocytes, CD115 positive monocytes (CD115 + monocytes) or combinations thereof.

6 . The method of claim 4 , wherein the monocytes are infiltrating monocytes and become OPN expressing macrophages in the brain.

7 . The method of claim 3 , wherein the innate immune cells are phagocytic.

8 . The method of claim 3 , wherein the composition comprises glatiramer acetate (GA).

9 . The method of claim 3 , wherein the innate immune cells are stimulated ex vivo or in vivo.

10 . The method of claim 3 , wherein innate immune cells expressing OPN are administered to the subject by adoptive cell transfer or bone marrow transplantation.

11 . The method of claim 10 , wherein the innate immune cells over-express OPN.

12 . The method of claim 1 , wherein the composition is administered by a method selected from the group consisting of direct delivery to the subject, viral vector delivery, a liposomal delivery system, or nanodrug delivery system.

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

14 . The method of claim 1 , wherein the administration of the composition results in an increase in MMP-9.

15 . The method of claim 1 , wherein elevated OPN expression results in decreased levels of a misfolded protein in the subject.

16 . The method of claim 15 , wherein the misfolded protein is amyloid beta (Aβ).

17 . The method of claim 16 , wherein the Aβ is Aβ 40 and/or Aβ 42 .

18 . A method of improving cognitive function in a subject in need thereof, comprising:
providing a composition that, when administered to the subject, results in increased levels of osteopontin (OPN) relative to a normal subject; and administering an amount of the composition to the subject sufficient to increase said levels of OPN.

19 . The method of claim 18 , wherein the composition comprises OPN expressing innate immune cells, recombinant OPN, OPN fragments, OPN derivatives, OPN mimetics, OPN analogues or a combination thereof.

20 . The method of claim 18 , wherein the composition stimulates expression of OPN in innate immune cells.

21 . The method of claim 20 , wherein the innate immune cells comprise monocytes, macrophages or combinations thereof.

22 . The method of claim 21 , wherein the monocytes comprise bone marrow-derived monocytes, spleen-derived monocytes, CD115 positive monocytes (CD115 + monocytes) or combinations thereof.

23 . The method of claim 20 , wherein the monocytes are infiltrating monocytes and become OPN expressing macrophages in the brain.

24 . The method of claim 20 , wherein the innate immune cells are phagocytic.

25 . The method of claim 20 , wherein the composition comprises glatiramer acetate (GA).

26 . The method of claim 20 , wherein the innate immune cells are stimulated ex vivo or in vivo.

27 . The method of claim 20 , wherein innate immune cells expressing OPN are administered to the subject by adoptive cell transfer or bone marrow transplantation.

28 . The method of claim 27 , wherein the innate immune cells over-express OPN.

29 . The method of claim 18 , wherein the composition is administered by a method selected from the group consisting of direct delivery to the subject, viral vector delivery, a liposomal delivery system, or nanodrug delivery system.

30 . The method of claim 18 , wherein the administration of the composition results in an increase in MMP-9.

31 . The method of claim 18 , wherein increased levels of OPN 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.

32 . The method of claim 31 , wherein the misfolded protein is Aβ.

33 . The method of claim 32 , 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

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61K38/18

  Growth factors; Growth regulators · CPC title

• A61K38/19

  Cytokines; Lymphokines; Interferons · CPC title

• A61K31/7088

  Compounds having three or more nucleosides or nucleotides · CPC title