IP Library › Granted Patent US 7,427,598
Granted Patent B2
US 7,427,598 · App. 10/296,849 · Granted Sep 23, 2008

Post-natal administration of activity-dependent neurotrophic factor-derived polypeptides for enhancing learning and memory

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Quick Facts
Patent No.
US 7,427,598
App. No.
10/296,849
Granted
Sep 23, 2008
Kind
B2
Abstract

The present invention provides methods for improving performance (e.g. learning and/or memory) using (ADNF) polypeptides, by treating the subject prenatally or postnatally with an Activity Dependent Neurotrophic Factor (ADNF) polypeptide in an amount sufficient to improve postnatal learning and/or memory of the subject.

Claims (52)

1. A method for improving learning and memory in a subject, the method comprising the step of administering postnatally to the subject in an amount sufficient to improve postnatal learning and memory of the subject, a mixture of:

(a) an Activity Dependent Neurotrophic Factor (ADNF) I polypeptide comprising an active core site having the following amino acid sequence:

Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala (SEQ ID NO:1); and

(b) an Activity Dependent Neurotrophic Factor (ADNF) III polypeptide comprising an active core site having the following amino acid sequence:

Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln (SEQ ID NO:2); and

assessing learning and memory of the post-natal subject, wherein the active core site of at least one of the ADNF I polypeptide and the ADNF III polypeptide comprises all D-amino acids.

2. The method of claim 1 wherein the active core site of the ADNF I polypeptide comprises all D-amino acids.

3. The method of claim 1 , wherein the ADNF I polypeptide is Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala (SEQ ID NO:1).

4. The method of claim 1 , wherein the ADNF I polypeptide is selected from the group consisting of:

Val-Len-Gly-Gly-Gly- Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala (SEQ ID NO:14);

Val-Glu-Glu-Gly-Ile-Val-Leu-Gly-Gly-Gly-Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala (SEQ ID NO:15);

Leu-Gly-Gly-Gly- Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala (SEQ ID NO:16);

Gly-Gly-Gly-Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala (SEQ ID NO:17);

Gly-Gly-Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala (SEQ ID NO:18);

Gly- Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala (SEQ ID NO:19); and

Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala (SEQ ID NO:1).

5. The method of claim 1 , wherein the ADNF I polypeptide comprises up to about 20 amino acids at one or both of the N-terminus and the C-terminus of the active core site.

6. The method of claim 1 , wherein the active core site of the ADNF III polypeptide comprises all D-amino acids.

7. The method of claim 1 , wherein the ADNF III polypeptide is Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln (SEQ ID NO:2).

8. The method of claim 1 , wherein the ADNF III polypeptide is a member selected from the group consisting of:

Gly-Gly-Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln (SEQ ID NO:20);

Leu-Gly-Gly-Asn-Ala-Pro-Val-Ser-Ile-PrO-Gln-Gln-Ser (SEQ ID NO:21);

Leu-Gly-Leu-Gly-Gly-Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln-Gln-Ser (SEQ ID NO:22);

Ser-Val-Arg-Leu-Gly-Leu-Gly-Gly-Asn-Ala-Pro-Gln-Gln-Ser (SEQ ID NO:23); and

Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln (SEQ ID NO:2)

9. The method of claim 1 , wherein the ADNF III polypeptide comprises up to about 20 amino acids at one or both of the N-terminus and the C-terminus of the active core site.

10. The method of claim 1 , wherein the active core sites of both the ADNF I polypeptide and the ADNF III polypeptide comprise all D-amino acids.

11. The method of claim 1 , wherein the ADNF I polypeptide is Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala (SEQ ID NO:1), and wherein the ADNF III polypeptide is Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln (SEQ ID NO:2).

12. The method of claim 1 , wherein the ADNF I polypeptide is a member selected from the group consisting of:

Val-Leu-Gly-Gly-Gly- Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala (SEQ ID NO:14);

Val-Glu-Glu-Gly-Ile-Val-Leu-Gly-Gly-Gly-Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala (SEQ ID NO:15);

Leu-Gly-Gly-Gly- Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala (SEQ ID NO:16);

Gly-Gly-Gly-Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala (SEQ ID NO:17);

Gly-Gly-Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala (SEQ ID NO:18);

Gly- Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala (SEQ ID NO:19); and

Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala (SEQ ID NO:1); and

wherein the ADNF III polypeptide is selected from the group consisting of:

Gly-Gly-Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln (SEQ ID NO:20);

Leu-Gly-Gly-Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln-Gln-Ser (SEQ ID NO:21);

Leu-Gly-Leu-Gly-Gly-Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln-Gln-Ser (SEQ ID NO:22);

Ser-Val-Arg-Leu-Gly-Leu-Gly-Gly-Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln-Gln-Ser (SEQ ID NO:23); and

Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln (SEQ ID NO:2).

13. The method of claim 1 , wherein the ADNF I polypeptide comprises up to about 20 amino acids at one or both of the N-terminus and the C-terminus of the active core site of the ADNF I polypeptide, and wherein the ADNF III polypeptide comprises up to about 20 amino acids at one or both of the N-terminus and the C-terminus of the active core site of the ADNF III polypeptide.

14. The method of claim 1 , wherein the ADNF I polypeptide is a full length ADNF I polypeptide and the ADNF III polypeptide is a full length ADNF III polypeptide.

15. The method of claim 1 , wherein the subject is afflicted with a neuropathology.

16. The method of claim 1 , wherein the subject has Alzheimer's disease.

17. The method of claim 1 , wherein the subject has Down's syndrome.

18. The method of claim 1 , wherein the subject is normal.

19. The method of claim 18 , wherein the subject is old.

20. The method of claim 1 , wherein the method improves short term memory.

21. The method of claim 1 , wherein the method improves reference memory.

22. The method of claim 1 , wherein the mixture is administered intranasally or orally.