Prion protein antibodies for the treatment of Alzheimer's disease
The invention relates to a ligand capable of binding PrP at a site within amino acid residues 131 to 153 of PrP, for use in treatment or prevention of impaired synaptic plasticity. The invention also relates to a ligand capable of binding PrP at a site within amino acid residues 131 to 153 of PrP, for use in treatment or prevention of toxicity of Aβ oligomers. The invention also relates to a ligand capable of binding PrP at a site within amino acid residues 131 to 153 of PrP, for use in treatment or prevention of Alzheimer's Disease. The invention also relates to methods of medical treatment.
1. A method of treating Alzheimer's Disease in a subject, the method comprising administering to the subject a therapeutically effective amount of an-anti-prion protein (anti-PrP) antibody having the complementarity determining sequences (CDRs) DYNLD (amino acids 50 to 54 of SEQ ID NO:4), NVYPNNGVTGYNQKFRG (amino acids 69 to 85 of SEQ ID NO:4), YYYDVSY(amino acids 118 to 124 of SEQ ID NO:4), SASSSVSYMH (amino acids 46 to 55 of SEQ ID NO:6), DTSKLAS (amino acids 71 to 77 of SEQ ID NO:6), and HQWRSNPYT (amino acids 110 to 118 of SEQ ID NO:6) which specifically binds an epitope of human PrP within amino acids 109 to 131 of SEQ ID NO: 2.
2. The method of claim 1 , wherein the antibody is a monoclonal antibody, humanized antibody, chimeric antibody, scFv, Fab or other antigen binding fragment thereof.
3. The method of claim 2 , wherein the monoclonal antibody is ICSM 18, a humanized form thereof, or an antigen binding fragment thereof.
4. The method of claim 2 , wherein the monoclonal antibody is ICSM 18, or a humanized form thereof.
5. The method of claim 1 , further comprising administering an additional therapeutic agent.
6. The method of claim 1 , wherein the antibody is an immunoglobulin (Ig)G, IgE, IgM, IgD, IgA, or IgY.
7. The method of claim 6 wherein the antibody is an IgG1, IgG2, IgG3, IgG4, IgA1 or IgA2.
8. The method of claim 1 , wherein the antibody binds PrP at a site within amino acid residues 131 to 153 of PrP with an affinity of 100 nM or less.
9. The method of claim 1 wherein the antibody comprises SEQ ID NO: 4 and SEQ ID NO: 6.
10. The method of claim 1 , wherein the anti PrP antibody is administered at a dosage ranging from 0.0001 to 100 mg/kg.
11. The method of claim 1 , wherein the subject is a human subject.
12. The method of claim 1 , wherein the antibody is administered by subcutaneous injection, intravenously, by injection or infusion into the cerebrospinal fluid (CSF) or intracerebrally.
13. A method of inhibiting suppression of long-term potentiation in a subject, improving acute memory retention, improving spatial memory performance or improving acute memory retention and spatial memory performance, the method comprising
administering to a subject a therapeutically effective amount of an anti-PrP antibody having the complementarity determining sequences (CDRs) DYNLD (amino acids 50 to 54 of SEQ ID NO:4), NVYPNNGVTGYNQKFRG (amino acids 69 to 85 of SEQ ID NO:4), YYYDVSY(amino acids 118 to 124 of SEQ ID NO:4), SASSSVSYMH (amino acids 46 to 55 of SEQ ID NO:6), DTSKLAS (amino acids 71 to 77 of SEQ ID NO:6), and HQWRSNPYT (amino acids 110 to 118 of SEQ ID NO:6), which specifically binds an epitope of human PrP within amino acids 109 to 131 of SEQ ID NO: 2, wherein the subject has Alzheimer's Disease.
14. The method of claim 13 , wherein the antibody is a monoclonal antibody, humanized antibody, chimeric antibody, scFv, Fab or other antigen binding fragment thereof.
15. The method of claim 14 , wherein the monoclonal antibody is ICSM 18, a humanized form thereof, or an antigen binding fragment thereof.
16. The method of claim 14 , wherein the monoclonal antibody is ICSM 18, or a humanized form thereof.
17. The method of claim 13 , further comprising administering an additional therapeutic agent.
18. The method of claim 13 , wherein the antibody is an IgG, IgE, IgM, IgD, IgA, or IgY.
19. The method of claim 18 wherein the antibody is an IgG1, IgG2, IgG3, IgG4, IgA1 or IgA2.
20. The method of claim 13 , wherein the antibody binds PrP at a site within amino acid residues 131 to 153 of human PrP (SEQ ID NO: 1) with an affinity of 100 nM.
21. The method of claim 13 , wherein the antibody comprises SEQ ID NO: 4 and SEQ ID NO: 6.
22. The method of claim 13 , wherein the subject is a human subject.
23. The method of claim 13 , wherein the antibody is administered by subcutaneous injection, intravenously, by injection or infusion into the cerebrospinal fluid (CSF) or intracerebrally.
24. The method of claim 13 , wherein the anti PrP antibody is administered at a dosage ranging from 0.0001 to 100 mg/kg.