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).
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. A method of treating Alzheimer's Disease in a subject comprising administering to the 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) with one or two conservative substitutions therein, NVYPNNGVTGYNQKFRG (amino acids 69 to 85 of SEQ ID NO:4) with one or two conservative substitutions therein, YYYDVSY(amino acids 118 to 124 of SEQ ID NO:4) with one or two conservative substitutions therein, SASSSVSYMH (amino acids 46 to 55 of SEQ ID NO:6) with one or two conservative substitutions therein, DTSKLAS (amino acids 71 to 77 of SEQ ID NO:6) with one or two conservative substitutions therein, and HQWRSNPYT (amino acids 110 to 118 of SEQ ID NO:6), with one or two conservative substitutions therein, wherein the antibody binds at a site within amino acid residues 109 to 131 of SEQ ID NO:2.
4. The method of claim 2 , wherein the monoclonal antibody is ICSM 18, a humanized form thereof, or an antigen binding fragment thereof.
5. The method of claim 4 , wherein the monoclonal antibody is ICSM 18-or a humanized form thereof.
6. The method of claim 1 , further comprising administering an additional therapeutic agent to the subject.
7. The method of claim 1 , wherein the antibody comprises a human immunoglobulin (Ig)G, IgE, IgM, IgD, IgA, or IgY framework.
8. The method of claim 7 , wherein the antibody comprises a human IgG1, IgG2, IgG3, IgG4, IgA1 or IgA2 framework.
9. The method of claim 1 , wherein the anti-PrP antibody is administered at a dosage ranging from 0.0001 to 100 mg/kg.
10. The method of claim 3 , wherein the antibody is a monoclonal antibody, humanized antibody, chimeric antibody, scFv, Fab or other antigen binding fragment thereof.
11. 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.
12. The method of claim 3 , wherein the antibody comprises a human IgG, IgE, IgM, IgD, IgA, or IgY framework.
13. The method of claim 12 , wherein the antibody comprises a human IgG1, IgG2, IgG3, IgG4, IgA1 or IgA2 framework.
14. The method of claim 3 , wherein the anti-PrP antibody is administered at a dosage ranging from 0.0001 to 100 mg/kg.
15. The method of claim 3 , wherein the antibody is a monoclonal antibody, a humanized form thereof, or an antigen binding fragment thereof.
16. The method of claim 3 , wherein the antibody is administered by subcutaneous injection, intravenously, by injection or infusion into the cerebrospinal fluid (CSF) or intracerebrally.
17. The method of claim 3 , wherein the antibody is a monoclonal antibody or a humanized form thereof.