Growth factors nsg28, nsg30, and nsg32

• US 20090136552A1
• Filed: 08/01/2005
• Published: 05/28/2009
• Est. Priority Date: 07/30/2004
• Status: Abandoned Application

• Current Assignee: NsGene A/S
• Original Assignee: NsGene A/S
• Inventors: Petersen, Thomas Nordahl, Johansen, Teit E., Blom, Nikolaj, Brunak, Soren, Wahlberg, Lars U., Kusk, Philip, Gronborg, Mette
• Application Number:
  US11/659,016
• Publication Number:
  US 20090136552A1
• Time in Patent Office: Days
• US Class Current: 424/422
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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: C07K 14/475 Growth factors; Growth regulators

Abstract

Disclosed are NsG28, NsG30, NsG32 polypeptides, nucleic acids encoding NsG28, NsG30, NsG32 polypeptides, and antibodies that bind to NsG28, NsG30, NsG32 polypeptides as well as methods of making and using the same.

Claims

1. An isolated polypeptide, said polypeptide comprising an amino acid sequence selected from the group consisting of:

a) the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41;

b) a sequence variant of the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41, wherein the variant has at least 90% sequence identity to said SEQ ID NO; and

c) a biologically active fragment of at least 50 contiguous amino acids of any of a) through b).

2. The polypeptide of claim 1 that is a naturally occurring allelic variant of the sequence selected from the group consisting of SEQ ID NO 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41.

3. The polypeptide of claim 2, wherein the allelic variant comprises an amino acid sequence that is the translation of a nucleic acid sequence differing by a single nucleotide from a nucleic acid sequence selected from the group consisting of SEQ ID NO 2, 8, 17, 22, 26, 30, 35, 37, and 39.

4. The polypeptide of claim 1 that is a variant polypeptide described therein, wherein any amino acid specified in the chosen sequence is changed to provide a conservative substitution.

5. The polypeptide of claim 1, wherein the signal peptide has been replaced by a heterologous signal peptide.

7. The polypeptide of claim 1, having at least 90% sequence identity to a protein having a sequence selected from the group consisting of SEQ ID NO 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41.

8. The polypeptide of claim 1, having at least 95% sequence identity to a protein having a sequence selected from the group consisting of SEQ ID NO 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41.

9. The polypeptide of claim 1, having at least 98% sequence identity to a protein having a sequence selected from the group consisting of SEQ ID NO 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41.

10. The polypeptide of claim 1, wherein the fragment is selected from the group consisting of:

i) SEQ ID No 6, and polypeptides having from one to five additional amino acids from the mature polypeptide sequence in the C or N-terminal, or both, up to AA₁₄-AA₉₈ of SEQ ID No 5;

ii) SEQ ID No 11 and polypeptides having from one to five additional amino acids from the mature polypeptide sequence in the C or N-terminal, or both, up to AA₁₄-AA₉₈ of SEQ ID No 10;

iii) SEQ ID No 15 and polypeptides having from one to five additional amino acids from the mature polypeptide sequence in the C or N-terminal, or both, up to AA₁₄-AA₉₈ of SEQ ID No 14

iv) SEQ ID No 20, and polypeptides having from one to five additional amino acids from the mature polypeptide sequence in the or N-terminal, or both, up to AA₉-AA₉₃ of SEQ ID No 19 or 24;

v) SEQ ID No 34, and polypeptides having from one to five additional amino acids from the mature polypeptide sequence in the C and/or N-terminal, or both, up to AA₈-AA₉₂ of SEQ ID No 32; and

vi) variants of said polypeptides, wherein any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 10 of the amino acid residues in the sequence are so changed.

11. The polypeptide of claim 1, wherein the polypeptide is selected from the group consisting of:

i) SEQ ID No 7, and polypeptides having from one to five additional amino acids from the mature polypeptide sequence in the C or N-terminal, or both, up to AA₁₂-AA₁₀₆ of SEQ ID No 5;

ii) SEQ ID No 12 and polypeptides having from one to five additional amino acids from the mature polypeptide sequence in the C or N-terminal, or both, up to AA₁₂-AA₁₀₆ of SEQ ID No 10;

iii) SEQ ID No 16 and polypeptides having from one to five additional amino acids from the mature polypeptide sequence in the C or N-terminal, or both, up to AA₁₂-AA₁₀₅ of SEQ ID No 14;

iv) SEQ ID No 21, and polypeptides having from one to five additional amino acids from the mature polypeptide sequence in the C or N-terminal, or both, up to AA₇-AA₁₀₁ of SEQ ID No 19 or 24;

v) SEQ ID No 33, and polypeptides having from one to five additional amino acids from the mature polypeptide sequence in the C or N-terminal, or both, up to AA₆-AA₁₀₀ of SEQ ID No 32; and

vi) variants of said polypeptides, wherein any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 10 of the amino acid residues in the sequence are so changed.

12. The polypeptide of claim 1, wherein the changed amino acids are selected from those designated as unconserved, weakly conserved or strongly conserved in any of FIG. 11, 12, 13A, or 13B.

13. The polypeptide of claim 1, wherein the changed amino acids are selected from those designated as unconserved, weakly conserved or strongly conserved in FIG. 1B, more preferably or in FIG. 1A.

14. The polypeptide of claim 1, wherein any changed amino acid residue is changed to a residue found at the same or corresponding position in another Cys10 protein (FIG. 1A or 1B).

15. The polypeptide of claim 1, wherein any changed amino acid residue is changed to a residue found at the same or corresponding position in another NsG28, NsG30, or NsG32.

16. The polypeptide of claim 1, comprising the conserved cysteine residues of the Cys10 family at positions corresponding to the position of mature NsG28, mature NsG30, or mature NsG32.

17. The polypeptide of claim 1, comprising the following sequence:

G-T-C-E-[V/I]-[V/I]-x(3)-R-x(5)-[R/K]-x(5)-Q-T-[V/A]-[K/R]-C-x-C-x(2)-G-x-[V/I]-A-G-T-T-R-x(2)-P-x-C-V-[D/E]-A-x-I-[V/I]-x(2)-[K/R]-x-W-C-x-M-x-P-C-L-x-G-E-x-C-x(2)-L-x(4)-G-W-x-C-x(2-3)-G-x-[K/R]-[V/I]-K-T-T.

18. The polypeptide of claim 17, comprising the following sequence:

G-T-C-E-V-[V/I]-A-x-H-R-C-C-N-[K/R]-N-[R/K]-I-E-E-R-S-Q-T-V-K-C-S-C-x(2)-G-x-V-A-G-T-T-R-x(2)-P-S-C-V-[D/E]-A-x-I-V-x(2)-[K/R]-W-W-C-x-M-x-P-C-L-x-G-E-[E/D]-C-K-x-L-P-D-x(2)-G-W-x-C-x-[S/T]-G-x-K-[V/I]-K-T-T-[R/K].

19. The polypeptide of claim 1, wherein said polypeptide is capable of forming at least one intramolecular cysteine bridge.

20. The polypeptide of claim 1, comprising a homodimer of NsG28, NsG30, NsG32a, or NsG32b linked through an intermolecular cysteine bridge.

21. The polypeptide of claim 1, comprising a heterodimer of (i) NsG28 and one of the other members of the Cys10 family, (ii) NsG30 and one of the other members of the Cys10 family, (iii) NsG32a and NsG32b, (iv) NsG32a and one of the other members of the Cys10 family, or (v) NsG32b and one of the other members of the Cys10 family linked through an intramolecular cysteine bridge.

22. The polypeptide according to claim 1, further comprising an affinity tag, selected from the group consisting of a polyhis tag, a GST tag, a HA tag, a Flag tag, a C-myc tag, a HSV tag, a V5 tag, a maltose binding protein tag, and a cellulose binding domain tag.

23. The polypeptide according to claim 1, wherein the polypeptide inhibits apoptosis.

57. A packaging cell line capable of producing an infective virus particle, said virus particle comprising a Retroviridae derived genome comprising a 5′

retroviral LTR, a tRNA binding site, a packaging signal, a promoter operably linked to a polynucleotide sequence encoding the polypeptide of any of claim 1, an origin of second strand DNA synthesis, and a 3′

retroviral LTR.

58. The packaging cell line of claim 57, wherein the genome is lentivirally derived and the LTRs are lentiviral.

100. An antibody capable of binding to a polypeptide of claim 1.

101. The antibody of claim 100, being wherein the antibody is selected from the group consisting of:

polyclonal antibodies, monoclonal antibodies, humanised antibodies, single chain antibodies, and recombinant antibodies.

102. An immunoconjugate comprising the antibody of claim 100 and a conjugate selected from the group consisting of:

a cytotoxic agent such as a chemotherapeutic agent, a toxin, or a radioactive isotope;

a member of a specific binding pair, avidin, streptavidin or an antigen; and

an enzyme capable of producing a detectable product.

6. (canceled)

24. An isolated nucleic acid molecule for medical use comprising a nucleotide sequence selected from the group consisting of:

a) a nucleotide sequence coding for a polypeptide having the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41;

b) a nucleotide sequence coding for a sequence variant of the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41, wherein the variant has at least 90% sequence identity to said SEQ ID No.;

c) a nucleotide sequence coding for a biologically active fragment of at least 50 contiguous amino acids of any of a) through b);

d) a nucleotide sequence selected from the group consisting of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39;

e) a nucleotide sequence having at least 70% 90% sequence identity to a coding sequence selected from the group consisting of the coding sequence of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39;

f) a nucleic acid sequence of at least 150 contiguous nucleotides of a coding sequence selected from the group consisting of the coding sequence of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39;

g) the complement of a nucleic acid capable of hybridising hybridizing with a nucleic acid molecule having the sequence of the coding sequence of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39 under conditions of high stringency; and

h) the nucleic acid sequence of the complement of any of the above.

25. The nucleic acid molecule of claim 24, wherein the nucleic acid molecule comprises the nucleotide sequence of a naturally occurring allelic nucleic acid variant.

26. The nucleic acid molecule of claim 24 that encodes a variant polypeptide, wherein the variant polypeptide has the polypeptide sequence of a naturally occurring polypeptide variant.

27. The nucleic acid molecule of claim 24, wherein the nucleic acid molecule differs by a single nucleotide from a nucleic acid sequence selected from the group consisting of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39.

28. The nucleic acid molecule of claim 24, wherein the encoded polypeptide has at least 90% sequence identity to a protein having a sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41.

31. The nucleic acid molecule of claim 24, wherein the encoded polypeptide has at least 95% sequence identity to a protein having a sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41.

32. The nucleic acid molecule of claim 24, wherein the encoded polypeptide has at least 98% sequence identity to the protein having the sequence of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41.

33. The nucleic acid molecule of claim 24, wherein the nucleic acid molecule comprises a nucleotide sequence selected from the group consisting of

a) the nucleotide sequence selected from the group consisting of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39;

b) a nucleotide sequence having at least 70% 90% sequence identity to a nucleotide sequence selected from the group consisting of the coding sequence of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39;

c) a nucleic acid sequence of at least 150 contiguous nucleotides of a sequence selected from the group consisting of the coding sequence of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39;

d) the complement of a nucleic acid capable of hybridising hybridizing with nucleic acid having the sequence selected from the group consisting of the coding sequence of SEQ ID No.;

SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39 under conditions of high stringency; and

e) the nucleic acid sequence of the complement of any of the above.

36. The nucleic acid molecule of claim 24, comprising a nucleotide sequence having at least 90% sequence identity to the nucleic acid molecule having the sequence of the coding sequence of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39.

37. The nucleic acid molecule of claim 24, comprising a nucleotide sequence having at least 95% sequence identity to the nucleic acid molecule having the sequence of the coding sequence of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39.

38. The nucleic acid molecule of claim 24, comprising a nucleotide sequence having at least 98% sequence identity to the nucleic acid molecule having the sequence of the coding sequence of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39.

39. The nucleic acid molecule of claim 24, comprising the nucleotide sequence of nucleotides 466-888 of SEQ ID No. 2 (long human NsG28 CDS), nucleotides 481-888 of SEQ ID No. 2 (human NsG28 CDS), nucleotides 568-885 of SEQ ID No. 2 (human mature NsG28 CDS), nucleotides 622-846 of SEQ ID No. 2 (human NsG28 cys1-cys10 fragment CDS), nucleotides 616-876 of SEQ ID No. 2 (human NsG28 core fragment CDS), nucleotides 206-613 of SEQ ID No. 8 (mouse NsG28 CDS), nucleotides 293-610 of SEQ ID No. 8 (mouse mature NsG28 CDS), nucleotides 347-571 of SEQ ID No. 8 (mouse NsG28 cys1-cys10 fragment CDS), or nucleotides 341-601 of SEQ ID No. 8 (mouse NsG28 core fragment CDS).

40. The nucleic acid molecule of claim 24, comprising the nucleotide sequence of nucleotides 156-551 of SEQ ID No. 17 (human NsG30 CDS), nucleotides 246-548 of SEQ ID No. 17 (human mature NsG30 CDS), nucleotides 285-509 of SEQ ID No. 17 (human Cys1-Cys10 fragment CDS), nucleotides 279-539 of SEQ ID No. 17 (human core fragment CDS), nucleotides 367-762 of SEQ ID No. 22 (mouse NsG30 CDS), nucleotides 457-759 of SEQ ID No. 22 (mouse mature NsG30 CDS), nucleotides 496-720 of SEQ ID No. 22 (mouse cys1-cys10 fragment CDS), or nucleotides 490-750 of SEQ ID No. 22 (mouse core fragment CDS).

41. The nucleic acid molecule of claim 24, comprising the nucleotide sequence of nucleotides 167-511 of SEQ ID No. 26, nucleotides 113-511 of SEQ ID No. 26, nucleotides 242-508 of SEQ ID No. 26, nucleotides 74-418 of SEQ ID No. 35, nucleotides 20-418 of SEQ ID No. 35, nucleotides 149-415 of SEQ ID No. 35, nucleotides 95-472 of SEQ ID No. 30, nucleotides 206-430 of SEQ ID No. 30, nucleotides 200-463 of SEQ ID No. 30, nucleotides 170-469 of SEQ ID No. 30, nucleotides 168-545 of SEQ ID No. 37, nucleotides 243-542 of SEQ ID No. 37, nucleotides 279-503 of SEQ ID No. 37, or nucleotides 273-536 of SEQ ID No. 37.

42. The nucleic acid molecule of claim 24, wherein the nucleic acid molecule is codon optimized for expression in E. coli, Chinese Hamster, Baby Hamster, Yeast, insect or fungus.

43. The nucleic acid molecule of claim 24, wherein the nucleic acid molecule is a shuffled variant between (i) SEQ ID No 2 or 8 and a nucleic acid coding for NsG29, NsG30, NsG31, or NsG32, (ii) SEQ ID No 17 or 22 and a nucleic acid coding for NsG28, NsG29, NsG31, or NsG32, (iii) SEQ ID No 26 or 35 and a nucleic acid coding for NsG28, NsG29, NsG30, or NsG31, or (iv) SEQ ID No 30 or 37 and a nucleic acid coding for NsG28, NsG29, NsG30, or NsG31.

44. The nucleic acid molecule of claim 24, wherein the nucleic acid molecule is a shuffled variant between SEQ ID No 2 and 8, SEQ ID No 17 and 22, SEQ ID No 26 and 35, or SEQ ID No 30 and 37.

45. A vector comprising the nucleic acid molecule of claim 24.

46. The vector of claim 45, further comprising a promoter operably linked to the nucleic acid molecule.

47. The vector of claim 46, wherein the promoter is selected from the group consisting of:

CMV, human UbiC, JeT, RSV, Tet-regulatable promoter, Mo-MLV-LTR, Mx1, and EF-1alpha.

48. The vector of claim 45, wherein the vector is selected from the group consisting of vectors derived from the Retroviridae family including lentivirus, HIV, SIV, FIV, EAIV, and CIV.

49. The vector of claim 45, wherein the vector is selected from the group consisting of alphavirus, adenovirus, adeno associated virus, baculovirus, HSV, coronavirus, Bovine papilloma virus, and Mo-MLV.

50. An isolated host cell transformed or transduced with the vector of claim 45.

51. The host cell of claim 50, wherein the host cell is selected from the group consisting of E. coli, Yeast, Saccharomyces cerevisiae, Aspergillus, and Sf9 insect cells.

52. The host cell of claim 50, wherein the host cell is selected from the group consisting of mammalian cells, such as human, feline, porcine, simian, canine, murine, rat, mouse and rabbit cells.

53. The host cell of claim 52, wherein the host cell is selected from the group consisting of immortalized retinal pigmented epithelial cells, ARPE-19 cells, immortalised immortalized human fibroblasts, and immortalized human astrocytes.

54. The host cell of claim 53, wherein the host cell is attached to a matrix.

55. The host cell of claim 52, wherein the host cell is selected from the group consisting of stem cells, human neural stem cells, human neural precursor cells, human glial stem cells, human glial precursor cells, and fetal stem cells.

56. The host cell of claim 52, wherein the host cell is selected from the group consisting of CHO, CHO-K1, HEI193T, HEK293, COS, PC12, HiB5, RN33b, and BHK cells.

113. The vector of claim 46, wherein the vector is selected from the group consisting of vectors derived from the Retroviridae family including lentivirus, HIV, SIV, FIV, EAIV, and CIV.

114. The vector of claim 46, wherein the vector is selected from the group consisting of alphavirus, adenovirus, adeno associated virus, baculovirus, HSV, coronavirus, Bovine papilloma virus, and Mo-MLV.

115. An isolated host cell transformed or transduced with the vector of claim 46.

116. The host cell of claim 115, wherein the host cell is selected from the group consisting of E. coli, Yeast, Saccharomyces cerevisiae, Aspergillus, and Sf9 insect cells.

117. The host cell of claim 115, wherein the host cell is selected from the group consisting of mammalian, human, feline, porcine, simian, canine, murine, rat, mouse and rabbit cells.

118. The host cell of claim 117, wherein the host cell is selected from the group consisting of immortalized retinal pigmented epithelial cells, ARPE-19 cells, immortalized human fibroblasts, and immortalized human astrocytes.

119. The host cell of claim 118, wherein the host cell is attached to a matrix.

120. The host cell of claim 115, wherein the host cell is selected from the group consisting of stem cells, human neural stem cells, human neural precursor cells, human glial stem cells, human glial precursor cells, and fetal stem cells.

121. The host cell of claim 115, wherein the host cell is selected from the group consisting of CHO, CHO-K1, HEI193T, HEK293, COS, PC12, HiB5, RN33b, and BHK cells.

122. The host cell of claim 115, wherein the vector comprises a promoter selected from the group consisting of:

CMV, human UbiC, JeT, RSV, Tet-regulatable promoter, Mo-MLV-LTR, Mx1, and EF-1 alpha.

123. The host cell of claim 122, wherein the vector is selected from the group consisting of vectors derived from the Retroviridae family including lentivirus, HIV, SIV, FIV, EAIV, and CIV.

124. The host cell of claim 123, wherein the vector is selected from the group consisting of alpha virus, adenovirus, adeno associated virus, baculovirus, HSV, coronavirus, Bovine papilloma virus, and Mo-MLV.

29. (canceled)

30. (canceled)

34. (canceled)

35. (canceled)

59. An implantable biocompatible cell device, the device comprising:

i) a semipermeable membrane permitting the diffusion of a polypeptide comprising an amino acid sequence selected from the group consisting of;

A) the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41;

B) a sequence variant of the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41, wherein the variant has at least 90% sequence identity to said SEQ ID NO; and

C) a biologically active fragment of at least 50 contiguous amino acids of any of A) through B) a virus, a vector or both; and

ii) a core containing cells transformed or transduced with a vector comprising a nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of;

A) a nucleotide sequence coding for a polypeptide having the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41;

B) a nucleotide sequence coding for a sequence variant of the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41, wherein the variant has at least 90% sequence identity to said SEQ ID No.;

C) a nucleotide sequence coding for a biologically active fragment of at least 50 contiguous amino acids of any of A) through B);

D) a nucleotide sequence selected from the group consisting of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39;

E) a nucleotide sequence having at least 90% sequence identity to a coding sequence selected from the group consisting of the coding sequence of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39;

F) a nucleic acid sequence of at least 150 contiguous nucleotides of a coding sequence selected from the group consisting of the coding sequence of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39;

G) the complement of a nucleic acid capable of hybridising hybridizing with a nucleic acid molecule having the sequence of the coding sequence of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39 under conditions of high stringency; and

H) the nucleic acid sequence of the complement of any of the above;

or a packaging cell line capable of producing an infective virus particle, said virus particle comprising a Retroviridae derived genome comprising a 5′

retroviral LTR, a tRNA binding site, a packaging signal, a promoter operably linked to a polynucleotide sequence encoding a polypeptide comprising the amino acid sequence described in i).

60. The device of claim 59, wherein the semipermeable membrane is immunoisolatory.

61. The device of claim 59, wherein the semipermeable membrane is microporous.

62. The device of claim 59, wherein the device further comprises a matrix disposed within the semipermeable membrane.

63. The device of claim 59, wherein the device further comprises a tether anchor.

64. The device of claim 59, wherein said core comprises living packaging cells that secrete a viral vector for infection of a target cell, wherein the viral vector is a retrovirus, wherein the promoter regulates the expression of said polypeptide in the target cell;

and wherein said semipermeable membrane comprises a permeable biocompatible material, said material having a porosity selected to permit passage of retroviral vectors of approximately 100 nm diameter thereacross, thereby permitting release of said viral vector from said capsule.

65. The device of claim 64, wherein the core additionally comprises a matrix and the packaging cells are immobilized by the matrix.

66. The device of claim 64, wherein the semipermeable membrane comprises a hydrogel or thermoplastic material.

67. A pharmaceutical composition comprising

i) a polypeptide comprising an amino acid sequence selected from the group consisting of:

A) the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41;

B) a sequence variant of the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41, wherein the variant has at least 90% sequence identity to said SEQ ID NO; and

C) a biologically active fragment of at least 50 contiguous amino acids of any of A) through B);

or

ii) an isolated nucleic acid sequence of comprising a nucleotide sequence selected from the group consisting of;

A) a nucleotide sequence coding for a polypeptide having the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41;

B) a nucleotide sequence coding for a sequence variant of the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41, wherein the variant has at least 90% sequence identity to said SEQ ID No.;

C) a nucleotide sequence coding for a biologically active fragment of at least 50 contiguous amino acids of any of A) through B);

D) a nucleotide sequence selected from the group consisting of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39;

E) a nucleotide sequence having at least 90% sequence identity to a coding sequence selected from the group consisting of the coding sequence of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39;

F) a nucleic acid sequence of at least 150 contiguous nucleotides of a coding sequence selected from the group consisting of the coding sequence of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39;

G) the complement of a nucleic acid capable of hybridising hybridizing with a nucleic acid molecule having the sequence of the coding sequence of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39 under conditions of high stringency; and

H) the nucleic acid sequence of the complement of any of the above;

or

iii) an expression vector comprising the isolated nucleic acid sequence described in ii);

or

iv) a composition of host cells transformed or transduced with the vector described in iii);

or

v) a packaging cell line capable of producing an infective virus particle, said virus particle comprising a Retroviridae-derived genome comprising a 5′

retroviral LTR, a tRNA binding site, a packaging signal, a promoter operably linked to a polynucleotide sequence encoding the polypeptide described in i), an origin of second strand DNA synthesis, and a 3′

retroviral LTR;

or

vi) an implantable biocompatible cell device according to claim 59; and

vii) a pharmaceutically acceptable carrier.

82. A method of treatment of a pathological condition in a subject comprising administering to an individual in need thereof a therapeutically effective amount of:

i.) a polypeptide of comprising an amino acid sequence selected from the group consisting of;

A) the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41;

B) a sequence variant of the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41, wherein the variant has at least 90% sequence identity to said SEQ ID NO; and

C) a biologically active fragment of at least 50 contiguous amino acids of any of A) through B);

or

ii) an isolated nucleic acid sequence of comprising a nucleotide sequence selected from the group consisting of;

A) a nucleotide sequence coding for a polypeptide having the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41;

B) a nucleotide sequence coding for a sequence variant of the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41, wherein the variant has at least 90% sequence identity to said SEQ ID No.;

C) a nucleotide sequence coding for a biologically active fragment of at least 50 contiguous amino acids of any of A) through B);

D) a nucleotide sequence selected from the group consisting of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39;

E) a nucleotide sequence having at least 90% sequence identity to a coding sequence selected from the group consisting of the coding sequence of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39;

F) a nucleic acid sequence of at least 150 contiguous nucleotides of a coding sequence selected from the group consisting of the coding sequence of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39;

G) the complement of a nucleic acid capable of hybridising hybridizing with a nucleic acid molecule having the sequence of the coding sequence of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39 under conditions of high stringency; and

H) the nucleic acid sequence of the complement of any of the above;

or

iii) an expression vector comprising the isolated nucleic acid sequence described in ii);

or

iv) a composition of host cells transformed or transduced with the vector described in iii);

or

v) a packaging cell line capable of producing an infective virus particle, said virus particle comprising a Retroviridae-derived genome comprising a 5′

retroviral LTR, a tRNA binding site, a packaging signal, a promoter operably linked to a polynucleotide sequence encoding the polypeptide described in i), an origin of second strand DNA synthesis, and a 3′

retroviral LTR;

or

vi) an implantable biocompatible cell device according to claim 59.

83. The method of claim 82, wherein the pathological condition is a disease, disorder, or damage associated with the nervous system.

84. The method of claim 83, wherein said disease, disorder, or damage associated with the nervous system involves injury to the brain, brain stem, the spinal cord, peripheral nerves, or a combination thereof, or is selected from the group consisting of stroke, traumatic brain injury, spinal cord injury, diffuse axonal injury, epilepsy, neuropathy, peripheral neuropathy and associated pain and other symptoms.

85. The method of claim 84, wherein said disorder is thalamic pain.

86. The method of claim 83, wherein the disease, disorder, or damage associated with the nervous system involves degeneration of neurons and their processes in the brain, brain stem, the spinal cord, the peripheral nerves, or a combination thereof, or is selected from the group consisting of Parkinson'"'"'s Disease, Alzheimer'"'"'s Disease, senile dementia, Huntington'"'"'s Disease, amyotrophic lateral sclerosis, neuronal injury associated with multiple sclerosis, and associated symptoms.

87. The method of claim 83, wherein the disease, disorder, or damage associated with the nervous system involves dysfunction or loss or both of neurons in the brain, brain stem, the spinal cord, the peripheral nerves, or a combination thereof, or is selected from the group consisting of conditions caused by metabolic diseases, nutritional deficiency, toxic injury, malignancy, genetic or idiopathic conditions, diabetes, renal dysfunction, alcoholism, chemotherapy, chemical agents, drug abuse, vitamin deficiency, infection and combinations thereof.

88. The method of claim 87, wherein the disease is essential tremor.

89. The method of claim 87, wherein the disease is peripheral neuropathy and associated pain.

90. The method of claim 83, wherein the disease, disorder, or damage associated with the nervous system involves the Cerebellum, or is selected from the group consisting of multiple sclerosis, neurodegenerative spinocerebellar disorders, hereditary ataxia, cerebellar atrophies (such as Olivopontocerebellar Atrophy (OPCA), Shy-Drager Syndrome (multiple systems atrophy)), and alcoholism.

91. The method of claim 83, wherein the disease, disorder, or damage associated with the nervous system involves degeneration or sclerosis of glia such as oligodendrocytes, astrocytes and Schwann cells in the brain, brain stem, the spinal cord, and the peripheral nerves, or a combination thereof, or is selected from the group consisting of multiple sclerosis, optic neuritis, cerebral sclerosis, post-infectious encephalomyelitis, and epilepsy and associated symptoms.

92. The method of claim 91, wherein said disorder is multiple sclerosis.

93. The method of claim 83, wherein the disease, disorder, or damage associated with the nervous system disorder, disease, or damage involves the retina, photoreceptors, and associated nerves, or a combination thereof, or is selected from the group consisting of including but not limited to retinitis pigmentosa, macular degeneration, glaucoma, diabetic retinopathy, and associated symptoms.

94. The method of claim 83, wherein the disease, disorder, or damage associated with the nervous system disorder, disease, or damage involves the sensory epithelium and associated ganglia of the vestibuloacoustic complex, or is selected from the group consisting of noise-induced hearing loss, deafness, tinnitus, otitis, labyrintitis, hereditary and cochleovestibular atrophies, Menieres Disease, and associated symptoms.

95. The method of claim 82, wherein the pathological condition is a disease related to testis, selected from the group consisting of male sterility, impotence, erectile dysfunction, cancer, and germ cell tumours.

96. The method of claim 82, wherein the subject is a human being.

97. The use of

ii) a polypeptide of comprising an amino acid sequence selected from the group consisting of:

A) the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41;

B) a sequence variant of the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41, wherein the variant has at least 90% sequence identity to said SEQ ID NO; and

C) a biologically active fragment of at least 50 contiguous amino acids of any of A) through B);

or

ii) an isolated nucleic acid sequence of comprising a nucleotide sequence selected from the group consisting of;

A) a nucleotide sequence coding for a polypeptide having the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41;

B) a nucleotide sequence coding for a sequence variant of the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41, wherein the variant has at least 90% sequence identity to said SEQ ID No.;

C) a nucleotide sequence coding for a biologically active fragment of at least 50 contiguous amino acids of any of A) through B);

D) a nucleotide sequence selected from the group consisting of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39;

E) a nucleotide sequence having at least 90% sequence identity to a coding sequence selected from the group consisting of the coding sequence of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39;

F) a nucleic acid sequence of at least 150 continuous nucleotides of a coding sequence selected from the group consisting of the coding sequence of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39;

G) the complement of a nucleic acid capable of hybridising hybridizing with a nucleic acid molecule having the sequence of the coding sequence of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39 under conditions of high stringency; and

H) the nucleic acid sequence of the complement of any of the above;

or

iii) an expression vector of comprising the isolated nucleic acid sequence described in ii);

or

iv) a composition of host cells according to transformed or transduced with the vector described in iii);

or

v) an implantable biocompatible cell device according to claim 59;

as a male contraceptive.

68-81. -81. (canceled)

98. A method of expanding a composition of mammalian cells, comprising administering to said composition a polypeptide of comprising an amino acid sequence selected from the group consisting of:

A) the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41;

B) a sequence variant of the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41, wherein the variant has at least 90% sequence identity to said SEQ ID NO; and

C) a biologically active fragment of at least 50 contiguous amino acids of any of A) through B),

or transducing/transfecting the cells with an expression vector comprising an isolated nucleic acid sequence, wherein the isolated nucleic acid sequence comprises a nucleotide sequence selected from the group consisting of;

A) a nucleotide sequence coding for a polypeptide having the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41;

B) a nucleotide sequence coding for a sequence variant of the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41, wherein the variant has at least 90% sequence identity to said SEQ ID No.;

;

C) a nucleotide sequence coding for a biologically active fragment of at least 50 contiguous amino acids of any of A) through B);

D) a nucleotide sequence selected from the group consisting of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39;

E) a nucleotide sequence having at least 90% sequence identity to a coding sequence selected from the group consisting of the coding sequence of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39;

F) a nucleic acid sequence of at least 150 contiguous nucleotides of a coding sequence selected from the group consisting of the coding sequence of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39;

G) the complement of a nucleic acid capable of hybridising hybridizing with a nucleic acid molecule having the sequence of the coding sequence of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39 under conditions of high stringency; and

H) the nucleic acid sequence of the complement of any of the above.

99. A method of differentiating a composition of mammalian cells, comprising administering to said composition a polypeptide of comprising an amino acid sequence selected from the group consisting of:

A) the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41;

B) a sequence variant of the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41, wherein the variant has at least 90% sequence identity to said SEQ ID NO; and

C) a biologically active fragment of at least 50 contiguous amino acids of any of A) through B);

or transducing/transfecting the cells with the an expression vector of comprising an isolated nucleic acid sequence, wherein the isolated nucleic acid sequence comprises a nucleotide sequence selected from the group consisting of;

A) a nucleotide sequence coding for a polypeptide having the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41;

B) a nucleotide sequence coding for a sequence variant of the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41, wherein the variant has at least 90% sequence identity to said SEQ ID No.;

C) a nucleotide sequence coding for a biologically active fragment of at least 50 contiguous amino acids of any of A) through B);

D) a nucleotide sequence selected from the group consisting of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39;

E) a nucleotide sequence having at least 90% sequence identity to a coding sequence selected from the group consisting of the coding sequence of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39;

F) a nucleic acid sequence of at least 150 contiguous nucleotides of a coding sequence selected from the group consisting of the coding sequence of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39;

G) the complement of a nucleic acid capable of hybridising hybridizing with a nucleic acid molecule having the sequence of the coding sequence of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39 under conditions of high stringency, and

H) the nucleic acid sequence of the complement of any of the above.

103. An isolated polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID No. 6, 7, 11, 12, 15, 16, 20, 21, 33, and 34, wherein any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15 of the amino acid residues in the sequence are so changed.

104. The polypeptide of claim 103, wherein no more than 10 of the amino acid residues in the chosen sequence are changed.

105. The isolated polypeptide of claim 103, wherein the changed amino acids are selected from those designated as unconserved, weakly conserved or strongly conserved in any of FIG. 11, 12, 13A, or 13B.

106. The isolated polypeptide of claim 103, wherein the changed amino acids are selected from those designated as unconserved, weakly conserved or strongly conserved in FIG. 1B, or FIG. 1A.

107. The isolated polypeptide of claim 103, further comprising up to 5 additional amino acids in the C- or N-terminal, the additional amino acids preferably being selected from the amino acids at corresponding positions in mature NsG28, mature NsG30, or mature NsG32b.

108. An isolated polynucleotide coding for a polypeptide comprising an amino acid sequence selected from the group consisting of:

A) the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41;

B) a sequence variant of the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41, wherein the variant has at least 90% sequence identity to said SEQ ID NO;

C) a biologically active fragment of at least 50 contiguous amino acids of any of A) through B); and

D) an amino acid sequence selected from the group consisting of SEQ ID No. 6, 7, 11, 12, 15, 16, 20, 21, 33, and 34, wherein any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15 of the amino acid residues in the sequence are so changed.

109. A method of preventing apoptosis in a neuronal cell, the method comprising contacting a neuronal cell with an affective amount of:

i) a polypeptide according to comprising an amino acid sequence selected from the group consisting of;

A) the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41,

B) a sequence variant of the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41, wherein the variant has at least 90% sequence identity to said SEQ ID NO; and

C) a biologically active fragment of at least 50 contiguous amino acids of any of A) through B);

ii) a nucleic acid according to sequence selected from the group consisting of;

A) a nucleotide sequence coding for a polypeptide having the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41;

B) a nucleotide sequence coding for a sequence variant of the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41, wherein the variant has at least 90% sequence identity to said SEQ ID No.;

C) a nucleotide sequence coding for a biologically active fragment of at least 50 contiguous amino acids of any of A) through B);

D) a nucleotide sequence selected from the group consisting of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39;

E) a nucleotide sequence having at least 90% sequence identity to a coding sequence selected from the group consisting of the coding sequence of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39;

F) a nucleic acid sequence of at least 150 contiguous nucleotides of a coding sequence selected from the group consisting of the coding sequence of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39;

G) the complement of a nucleic acid capable of hybridising hybridizing with a nucleic acid molecule having the sequence of the coding sequence of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39 under conditions of high stringency and

H) the nucleic acid sequence of the complement of any of the above; and

iii) a vector according to comprising the nucleic acid sequence described in ii).

110. A method of treating a disorder characterized by neuronal apoptosis, the method comprising administering to a subject having a disorder characterized by neuronal apoptosis a therapeutically affective amount of:

i) a polypeptide according to comprising an amino acid sequence selected from the group consisting of;

A) the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41;

B) a sequence variant of the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41, wherein the variant has at least 90% sequence identity to said SEQ ID NO; and

C) a biologically active fragment of at least 50 contiguous amino acids of any of A) through B);

ii) a nucleic acid according to sequence selected from the group consisting of;

A) a nucleotide sequence coding for a polypeptide having the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41;

B) a nucleotide sequence coding for a sequence variant of the amino acid sequence selected from the group consisting of SEQ ID No. 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 23, 24, 25, 27, 28, 29, 31, 32, 33, 34, 36, 38, 40, and 41, wherein the variant has at least 90% sequence identity to said SEQ ID No.

C) a nucleotide sequence coding for a biologically active fragment of at least 50 contiguous amino acids of any of A) through B);

D) a nucleotide sequence selected from the group consisting of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39;

E) a nucleotide sequence having at least 90% sequence identity to a coding sequence selected from the group consisting of the coding sequence of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39;

F) a nucleic acid sequence of at least 150 contiguous nucleotides of a coding sequence selected from the group consisting of the coding sequence of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39;

G) the complement of a nucleic acid capable of hybridising hybridizing with a nucleic acid molecule having the sequence of the coding sequence of SEQ ID No. 2, 8, 17, 22, 26, 30, 35, 37, and 39 under conditions of high stringency; and

H) the nucleic acid sequence of the complement of any of the above; and

iii) a vector according to comprising the nucleic acid sequence described in ii).

111. (canceled)

112. (canceled)