Treatment of demyelinating disorders with soluble lymphotoxin-β-receptor

1. A method of treating a demyelinating disorder in a human, the method comprising

(i) administering to a human an effective dose of a soluble Lymphotoxin-β-receptor (LTβR), and

(ii) monitoring the human for remyelination.

2. The method of claim 1 , wherein the soluble LTβR is administered to the human until remyelination is detected in the human.

3. The method of claim 1 , wherein the dose is administered once every 3-10 days; at least twice and not more than once every 5-20 days; or at least twice and not more than once every 28-31 days.

4. The method of claim 1 , wherein the dose is administered weekly, biweekly or monthly.

5. The method of claim 1 , wherein the dose is administered weekly over the course of at least 4 weeks.

6. The method of claim 1 , wherein the soluble LTβR is human LTβR or an LT-binding fragment thereof.

7. The method of claim 6 , wherein the soluble LTβR comprises an LT-binding fragment of the extracellular region of human LTβR (SEQ ID NO: 2) linked to an Fc region of an Ig.

8. The method of claim 7 , wherein the soluble LTβR comprises the sequence set forth in SEQ ID NO:1.

9. The method of claim 1 , wherein remyelination is monitored by an improvement of a symptom of a demyelinating disorder.

10. The method of claim 1 , wherein the demyelinating disorder is Multiple Sclerosis.

11. The method of claim 1 , wherein the demyelinating disorder is selected from the group consisting of Relapsing/Remitting Multiple Sclerosis, Secondary Progressive Multiple Sclerosis, Progressive Relapsing Multiple Sclerosis, Primary Progressive Multiple Sclerosis, and Acute Fulminant Multiple Sclerosis.

12. The method of claim 1 , wherein the demyelinating disorder is selected from the group consisting of Central Pontine Myelinolysis, Acute Disseminated Encephalomyelitis, Progressive Multifocal Leukoencephalopathy; Subacute Sclerosing Panencephalitis, Post-infectious Encephalomyelitis, Chronic Inflammatory Demyelinating Polyneuropathy, Guillain-Barre Syndrome, Progressive Multifocal Leucoencephalopathy, Devic's Disease, Balo's Concentric Sclerosis, and a leukodystrophy.

13. A method of treating a demyelinating disorder in a human, the method comprising administering to a human a dose of a soluble LTβR, wherein the unit dosage, frequency of administration, and duration of treatment is sufficient such that remyelination occurs in the human.

14. A method of promoting remyelination, the method comprising:

(i) administering to a human receiving an anti-TNF-therapy a dose of a soluble LTβR, and

(ii) monitoring the human for remyelination.

15. The method of claim 14 , wherein the human has an autoimmune disease.

16. The method of claim 15 , wherein the autoimmune disease is rheumatoid arthritis.

17. The method of claim 14 , wherein the soluble LTβR is administered to the human until remyelination is detected in the human.

18. The method of claim 14 , wherein the soluble LTβR is human LTβR or a LT-binding fragment thereof.

19. The method of claim 14 , wherein the dose is administered once every 3-10 days; at least twice and not more than once every 5-20 days; or at least twice and not more than once every 28-31 days.

20. The method of claim 14 , wherein the dose is administered weekly, biweekly or monthly.

21. The method of claim 14 , wherein the dose is administered weekly over the course of at least 4 weeks.

22. The method of claim 18 , wherein the soluble LTβR comprises a substantial portion of the extracellular region of human LTβR (SEQ ID NO: 2) linked to an Fc region of an Ig.

23. The method of claim 22 , wherein the soluble LTβR comprises the sequence set forth in SEQ ID NO:1.

24. The method of claim 14 , wherein remyelination is monitored by an improvement of a symptom of a demyelinating disorder.

25. The method of claim 24 , wherein the symptom is impaired vision, numbness, weakness in extremities, tremors, heat intolerance, speech impairment, incontinence, or impaired proprioception.

26. A delivery device designed for subcutaneous or intramuscular administration of a dose of soluble LTβR sufficient to promote remyelination, to a human having a demyelinating disorder.

27. The delivery device of claim 26 , wherein the delivery device is used to deliver lyophilized soluble LTBR.

28. The delivery device of claim 26 , wherein the soluble LTβR is human LTβR or an LT-binding fragment thereof.

29. The delivery device of claim 28 , wherein the soluble LTβR comprises a substantial portion of the extracellular region of human LTβR (SEQ ID NO: 2) linked to an Fc region of an Ig.

30. The delivery device of claim 29 , wherein the soluble LTβR comprises the sequence set forth in SEQ ID NO:1.

31. The delivery device of claim 26 , wherein the delivery device is a syringe.

32. The delivery device of claim 26 , wherein the demyelinating disorder is Multiple Sclerosis.