Prevention of fetal alcohol syndrome and neuronal cell death with ADNF polypeptides

• US 7,863,247 B1
• Filed: 03/10/2000
• Issued: 01/04/2011
• Est. Priority Date: 03/12/1999
• Status: Expired due to Fees

• Current Assignee: Ramot University Authority For Applied Research and Industrial Development Limited, The Secretary United States Of The Government Human Services, United States Department Of Health And Human Services
• Original Assignee: Ramot University Authority For Applied Research and Industrial Development Limited
• Inventors: Brenneman, Douglas E., Spong, Catherine Y., Zamostiano, Rachel, Gozes, Illana, Bassan, Merav
• Primary Examiner(s): Chernyshev; Olga N
• Application Number:
  US09/936,888
• Time in Patent Office: 3,952 Days
• Field of Search: None
• US Class Current: 514/17.5
• CPC Class Codes: A61K 38/18 Growth factors; Growth regulators
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 25/32 Alcohol-abuse

Abstract

The invention relates to methods for reducing a condition associated with fetal alcohol syndrome in a subject who is exposed to alcohol in utero with an ADNF polypeptide (e.g, ADNF I polypeptides, ADNF III polypeptides, or mixtures of ADNF I and ADNF III polypeptides). In one embodiment, the present invention relates to methods for reducing a condition associated with fetal alcohol syndrome in a subject who is exposed to alcohol in utero with a mixture of ADNF I and ADNF III polypeptides. The present invention further relates to methods for reducing neuronal cell death by contacting neuronal cells with a mixture of ADNF I and ADNF III polypeptides. Still further, the present invention relates to a pharmaceutical composition comprising a mixture of ADNF I and ADNF III polypeptides.

Claims

1. A method for reducing a condition associated with fetal alcohol syndrome in a subject who is exposed to alcohol in utero, the method comprising the steps of:

(i) selecting a pregnant female having consumed alcohol during pregnancy in an amount sufficient to initiate a condition associated with fetal alcohol syndrome in the subject; and

(ii) administering to the subject an activity dependent neurotrophic factor (ADNF) polypeptide in an amount sufficient to reduce in the subject the condition associated with fetal alcohol syndrome,

wherein the ADNF polypeptide is a member selected from the group consisting of;

(a) an ADNF I polypeptide comprising an active core site having the amino acid sequence Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala (SEQ ID NO;

1);

(b) an ADNF III polypeptide comprising an active core site having the amino acid sequence Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln (SEQ ID NO;

2); and

(c) a mixture of the ADNF I polypeptide of (a) and the ADNF III polypeptide of (b).

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

(a) a full length ADNF I polypeptide,

(b) a full length ADNF III polypeptide, and

(c) a mixture of a full length ADNF I polypeptide and a full length ADNF III polypeptide.

3. The method of claim 1, wherein the ADNF polypeptide is an ADNF I polypeptide.

4. The method of claim 3, wherein the ADNF I polypeptide consists of the amino acid sequence Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala (SEQ ID NO:

1).

5. The method of claim 3, wherein the ADNF I polypeptide consists of an amino acid sequence selected from the group consisting of:

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

14);

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

15);

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

16);

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

17);

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

18); and

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

19).

6. The method of claim 3, wherein the ADNF I polypeptide comprises up to 20 amino acids at the N-terminus or the C-terminus of the active core site.

7. The method of claim 1, wherein the ADNF polypeptide is an ADNF III polypeptide.

8. The method of claim 7, wherein the ADNF III polypeptide consists of the amino acid sequence Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln (SEQ ID NO:

2).

9. The method of claim 7, wherein the ADNF III polypeptide consists of an amino acid sequence selected from the group consisting of:

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

20);

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

21);

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

22); and

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

23).

10. The method of claim 7, wherein the ADNF III polypeptide comprises up to 20 amino acids at the N-terminus or the C-terminus of the active core site.

11. The method of claim 1, wherein the ADNF polypeptide is a mixture of the ADNF I polypeptide of (a) and the ADNF III polypeptide of (b).

12. The method of claim 11, wherein the ADNF I polypeptide is consists of the amino acid sequence Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala (SEQ ID NO:

1), and wherein the ADNF III polypeptide consists of the amino acid sequence Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln (SEQ ID NO;

2).

13. The method of claim 11, wherein the ADNF I polypeptide consists of an amino acid sequence selected from the group consisting of:

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

14);

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

15);

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

16);

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

17);

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

18);

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

19); and

(g) Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala (SEQ ID NO;

1); and

wherein the ADNF III polypeptide consists of an amino acid sequence selected from the group consisting of;

(a) Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln (SEQ ID NO;

2);

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

20);

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

21);

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

22); and

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

23).

14. The method of claim 11, wherein the ADNF I polypeptide comprises up to 20 amino acids at the N-terminus or the C-terminus of the active core site of the ADNF I polypeptide, and wherein the ADNF III polypeptide comprises up to 20 amino acids at the N-terminus or the C-terminus of the active core site of the ADNF III polypeptide.

15. The method of claim 1, wherein the condition is decreased body weight of the subject.

16. The method of claim 1, wherein the condition is decreased brain weight of the subject.

17. The method of claim 1, wherein the condition is a decreased level of VIP mRNA or protein of the subject.

18. The method of claim 1, wherein the condition is decreased viability of the subject in utero.

19. The method of claim 1, wherein the condition is decreased learning.

20. The method of claim 1, wherein step (ii) comprises administering the ADNF polypeptide directly to the subject.

21. The method of claim 1, wherein step (ii) comprises administering the ADNF polypeptide to the pregnant female during pregnancy.