Use of IL-18BP isoforms for the treatment and/or prevention of neurological inflammatory diseases
View Patent ↗The invention relates to the use of an IL18-BP isoform that does not bind to IL18, or of an agonist thereof, for treatment or prevention of a neurological and/or inflammatory disease. Preferred isoforms for use in the frame of the invention include IL-18BPb and IL-18BPd.
1. A method of treating acute disseminated encephalomyelitis (ADEM), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), Guillain-Barré syndrome (GBS), peripheral neuropathy, traumatic nerve injury, traumatic brain injury or amyotrophic lateral sclerosis (ALS) comprising administering a composition comprising an IL-18 binding protein (IL-18BP) isoform to an individual having a disease selected from acute disseminated encephalomyelitis (ADEM), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), Guillain-Barré syndrome (GBS), peripheral neuropathy, traumatic nerve injury, traumatic brain injury or amyotrophic lateral sclerosis (ALS), wherein said composition is administered in an amount effective to treat said disease and said IL-18BP isoform is selected from the group consisting of:
(a) polypeptide comprising amino acids 1 to 113 of SEQ ID NO: 1;
(b) a polypeptide comprising amino acids 29 to 113 of SEQ ID NO: 1;
(c) a polypeptide comprising amino acids 78 to 113 of SEQ ID NO: 1;
(d) a polypeptide comprising amino acids 1 to 161 of SEQ ID NO: 2;
(e) a polypeptide comprising amino acids 29 to 161 of SEQ ID NO: 2; and
(f) a fusion protein comprising a polypeptide according to any one of (a)-(e).
2. The method according to claim 1 , wherein said IL-18BP isoform is fused to a carrier molecule, a peptide or a protein that promotes the crossing of the blood brain barrier.
3. The method according to claim 1 , wherein said IL-18BP isoform is PEGylated.
4. The method according to claim 2 , wherein said IL-18BP isoform is fused to an immunoglobulin (Ig) domain.
5. The method according to claim 1 , wherein said method further comprises the administration of a composition comprising a polypeptide selected from the group consisting of an interferon, osteopontin and clusterin.
6. The method according to claim 1 , wherein said IL-18BP isoform is administered in an amount of about 0.001 to 100 mg/kg of body weight.
7. The method according to claim 1 , wherein said IL-18BP isoform is administered in an amount of about 0.01 to 10 mg/kg of body weight.
8. The method according to claim 1 , wherein said IL-18BP isoform is administered in an amount of about 9, 8, 7, 6, 5, 4, 3, 2 or 1 mg/kg of body weight.
9. The method according to claim 1 , wherein said IL-18BP isoform is administered in an amount of about 0.1 to 1 mg/kg of body weight.
10. The method according to claim 1 , wherein said IL-18BP isoform is a polypeptide comprising amino acids 1 to 113 of SEQ ID NO: 1.
11. The method according to claim 1 , wherein said IL-18BP isoform is a polypeptide comprising amino acids 29 to 113 of SEQ ID NO: 1.
12. The method according to claim 1 , wherein said IL-18BP isoform is a polypeptide comprising amino acids 78 to 113 of SEQ ID NO: 1.
13. The method according to claim 1 , wherein said IL-18BP isoform is a polypeptide comprising amino acids 1 to 161 of SEQ ID NO: 2.
14. The method according to claim 1 , wherein said IL-18BP isoform is a polypeptide comprising amino acids 29 to 161 of SEQ ID NO: 2.
15. The method according to claim 2 , wherein said IL-18BP isoform is fused to a carrier molecule through a peptide linker comprising Glu-Phe-Met or Glu-Phe-Gly-Ala-Gly-Leu-Val-Leu-Gly-Gly-Gln-Phe-Met (SEQ ID NO: 13).
16. The method according to claim 1 , wherein said disease is acute disseminated encephalomyelitis (ADEM).
17. The method according to claim 1 , wherein said disease is chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).
18. The method according to claim 1 , wherein said disease is Guillain-Barré syndrome (GBS).
19. The method according to claim 1 , wherein said disease is traumatic nerve injury.
20. The method according to claim 1 , wherein said disease is peripheral neuropathy.
21. The method according to claim 1 , wherein said disease is traumatic brain injury.
22. The method according to claim 1 , wherein said disease is amyotrophic lateral sclerosis (ALS).
23. The method according to claim 5 , wherein said composition comprising a polypeptide selected from the group consisting of an interferon, osteopontin and clusterin is administered separately from a composition comprising an IL-18BP isoform.
24. The method according to claim 5 , wherein said composition comprising a polypeptide selected from the group consisting of an interferon, osteopontin and clusterin is administered in combination with a composition comprising an IL-18BP isoform.