Treatment and prevention of neurodegenerative diseases using gene therapy

• US 8,247,385 B2
• Filed: 02/04/2008
• Issued: 08/21/2012
• Est. Priority Date: 02/06/2007
• Status: Active Grant

• Current Assignee: Tai June Yoo
• Original Assignee: Tai June Yoo
• Inventors: Yoo, Tai June
• Primary Examiner(s): FALK, ANNE MARIE
• Application Number:
  US12/025,684
• Publication Number:
  US 20080292603A1
• Time in Patent Office: 1,660 Days
• Field of Search: None
• US Class Current: 514/44.R
• CPC Class Codes: A61K 2039/53 DNA (RNA) vaccination
• CPC Class Codes: A61K 2039/55522 Cytokines; Lymphokines; Interferons
• CPC Class Codes: A61K 2039/57 characterised by the type of response, e.g. Th1, Th2
• CPC Class Codes: A61K 39/0007 Nervous system antigens; Prions
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61N 1/327 for enhancing the absorption properties of tissue, e.g. by electroporation
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 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 Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/28 Antiandrogens

Abstract

Provided herein are compositions and methods for treating and/or preventing neurodegenerative disease, such as Alzheimer'"'"'s disease. In particular aspects, compositions administered herein encode a cellular immune response element. The compositions may be prepared and administered in such a manner that the cellular immune response element coding sequence is expressed in the subject to which the composition is administered. The compositions include expression systems, delivery systems, and certain cellular immune response element genes.

Claims

1. A method of treating or ameliorating Alzheimer'"'"'s disease in a mammal, consisting essentially of administering to said mammal in vivo, by intramuscular injection, a composition consisting essentially of one or more nucleic acids that induce a cellular immune response;

wherein said one or more nucleic acids encode one or more cytokines selected from the group consisting of interleukin-4 (IL-4), interleukin-10 (IL-10), and transforming growth factor-β

(TGF-β

), and wherein said one or more nucleic acids are vectors and each vector comprises a promoter operably linked to a sequence encoding said cytokine.

3. The method of claim 1, wherein said composition consists essentially of two or more nucleic acids encoding two or more cytokines selected from the group consisting of IL-4, IL-10, and TGF-β

.

4. The method of claim 1, wherein said mammal is a human.

5. The method of claim 1, wherein said promoter is suitable for expression in eukaryotic cells.

6. The method of claim 1, wherein said vector is selected from the group consisting of pVAXI, pUMCV, pGCy, and pLentilox-IRES-GFP.

7. The method of claim 4, wherein said administration results in the decrease of amyloid plaque accumulation in the brain of said human in comparison to said human before said administration.

2. A method of treating or ameliorating Alzheimer'"'"'s disease in a mammal, consisting essentially of administering to said mammal in vivo, by intramuscular injection, a composition consisting essentially of:

(i) one or more nucleic acids that induce a cellular immune response, wherein said one or more nucleic acids encode one or more cytokines selected from the group consisting of IL-4, IL-10 and TGF-β

; and

(ii) one or more nucleic acids selected from the group consisting of nucleic acids encoding apolipoprotein E-2 (ApoE-2), nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF),

wherein said one or more nucleic acids are vectors and each vector comprises a promoter operably linked to a sequence encoding said cytokine, ApoE-2, NGF, or BDNF.

8. A method of decreasing the level of amyloid proteins in the brain of a mammal, consisting essentially of administering to said mammal in vivo, by intramuscular injection, a composition consisting essentially of one or more nucleic acids that induce a cellular immune response;

wherein said one or more nucleic acids encode one or more cytokines selected from the group consisting of IL-4, IL-10, and TGF-β

, and

wherein said one or more nucleic acids are vectors and each vector comprises a promoter operably linked to a sequence encoding said cytokine.

9. A method of treating or ameliorating Alzheimer'"'"'s disease in a mammal, comprising administering to said mammal in vivo, by intramuscular injection, a composition comprising one or more nucleic acids that induce a cellular immune response, wherein:

(i) said one or more nucleic acids encode one or more cytokines selected from the group consisting of IL-4, IL-10, and TGF-β

;

(ii) said one or more nucleic acids are vectors and each vector comprises a promoter operably linked to a sequence encoding said cytokine; and

(iii) said composition does not comprise β

-amyloid or β

-amyloid_1-42.

10. The method of claim 9, wherein said composition further comprises one or more nucleic acids selected from the group consisting of nucleic acids encoding ApoE-2, nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF).