Treatment of central nervous system disorders by intranasal administration of immunoglobulin g
The present invention provides, among other aspects, methods and compositions for treating a central nervous system (CNS) disorder by delivering a therapeutically effective amount of a composition of pooled human immunoglobulin G (IgG) to the brain via intranasal administration of the composition directly to the olfactory epithelium of the nasal cavity. In particular, methods and compositions for treating Alzheimer's disease are provided.
1. A method for delivering pooled human immunoglobulin G (IgG) to the brain of the subject, the method comprising intranasally administering a composition comprising pooled human IgG to the subject, wherein at least 40% of the pooled human IgG administered to the subject contacts the contacts the upper third of the nasal cavity of the subject.
2. The method of claim 1 , wherein administering the composition comprises administration of a liquid drop of the composition directly onto the nasal epithelium of the subject.
3. The method of claim 1 , wherein administering the composition comprises directed administration of an aerosol of the composition to the nasal epithelium of the subject.
4. The method of claim 3 , wherein the aerosol of the composition is a liquid aerosol.
5. The method of claim 3 , wherein the aerosol of the composition is a powder aerosol.
6. The method of claim 1 , wherein the composition comprising pooled human IgG comprises at least 0.1% anti-amyloid β IgG.
7. The method of claim 1 , wherein the composition comprising pooled human IgG does not contain a permeability enhancer.
8. The method of claim 1 , wherein the composition comprising pooled human IgG consists essentially of pooled human IgG and an amino acid selected from the group consisting of glycine, histidine, and proline.
9. The method of claim 1 , wherein the composition comprising pooled human IgG is an aqueous composition comprising:
(a) from 10 mg/mL to 250 mg/mL pooled human IgG; and
(b) from 50 mM to 500 mM glycine.
10. The method of claim 1 , wherein at least 50% of the pooled human IgG administered to the subject contacts the upper third of the nasal cavity of the subject.
11. The method of claim 1 , wherein at least 60% of the pooled human IgG administered to the subject contacts the upper third of the nasal cavity of the subject.
12. The method of claim 1 , wherein at least 70% of the pooled human IgG administered to the subject contacts the upper third of the nasal cavity of the subject.
13. The method of claim 1 , wherein at least 50% of the pooled human IgG administered to the subject contacts the olfactory epithelium of the subject.
14. The method of claim 1 , wherein at least 60% of the pooled human IgG administered to the subject contacts the olfactory epithelium of the subject.
15. The method of claim 1 , wherein at least 70% of the pooled human IgG administered to the subject contacts the olfactory epithelium of the subject.