Treatment and delay of outset of synucleinopathic and amyloidogenic disease

• US 9,034,337 B2
• Filed: 02/23/2007
• Issued: 05/19/2015
• Est. Priority Date: 10/31/2003
• Status: Active Grant

• Current Assignee: Prothena Biosciences Limited, Regents of the University of California (University of California)
• Original Assignee: Prothena Biosciences Limited
• Inventors: Schenk, Dale B., Masliah, Eliezar, Buttini, Manuel J., Chilcote, Tamie J., Rockenstein, Edward, Games, Kate Dora
• Primary Examiner(s): BALLARD, KIMBERLY
• Application Number:
  US11/710,248
• Publication Number:
  US 20090208487A1
• Time in Patent Office: 3,007 Days
• Field of Search: None
• US Class Current: 424/185.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/55566 Emulsions, e.g. Freund's adjuvant, MF59
• CPC Class Codes: A61K 39/0007 Nervous system antigens; Prions
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues

Abstract

The invention provides improved agents and methods for treatment of diseases associated with synucleinopathic diseases, including Lewy bodies of alpha-synuclein in the brain of a patient. Such methods entail administering agents that induce a beneficial immunogenic response against the Lewy body. The methods are particularly useful for prophylactic and therapeutic treatment of Parkinson'"'"'s disease.

Claims

1. A method of reducing the risk of, lessening the severity of, delaying the outset of or treating a disease characterized by Lewy bodies or alpha-synuclein aggregation in the brain, the method comprising:

administering to a patient having or at risk of the disease an immunogenic fragment of alpha-synuclein consisting of 5-9 contiguous residues from between residues 118-126 of human alpha synuclein (SEQ ID NO;

1) effective to induce an immunogenic response comprising antibodies that specifically bind to an epitope within residues 118-126 of SEQ ID NO;

1, thereby reducing the risk of, lessening the severity of, delaying the outset of or treating the disease.

2. The method of claim 1, wherein the immunogenic fragment is SN118-126.

3. The method of claim 1, wherein the immunogenic fragment is linked to a carrier to form a conjugate.

4. The method of claim 3, wherein the carrier is a heterologous polypeptide.

5. The method of claim 3, wherein the carrier is a tetanus toxoid.

6. The method of claim 3, wherein the carrier is a diphtheria toxoid.

7. The method of claim 4, wherein the heterologous polypeptide comprises the amino acid sequence AKXVAAWTLKAAA (SEQ ID NO:

12).

8. The method of claim 1, wherein the disease is Parkinson'"'"'s disease.

9. The method of claim 1, wherein the immunogenic fragment is administered with a pharmaceutical carrier as a pharmaceutical composition.

10. The method of claim 1, wherein the immunogenic fragment is administered in combination with an adjuvant.

11. The method of claim 10, wherein the adjuvant is pharmaceutically acceptable for human administration.

12. The method of claim 10, wherein the adjuvant is selected from the group consisting of QS21, monophosphoryl lipid, alum, CpG, GM-CSF and M-CSF.

13. The method of claim 1, wherein the immunogenic fragment is administered at a dosage of 1-500 μ

g per injection.

14. The method of claim 1, wherein the immunogenic fragment is administered in multiple dosages over at least six months.

15. The method of claim 1, wherein the immunogenic fragment is administered intraperitoneally, subcutaneously, intramuscularly, intranasally or intravenously.