Method of treating neurologic disorders

• US 20030203881A1
• Filed: 03/06/2003
• Published: 10/30/2003
• Est. Priority Date: 09/06/2000
• Status: Abandoned Application

• Current Assignee: Neurotherapeutics, LLC
• Original Assignee: Neurotherapeutics, LLC
• Inventors: Duncan, Ian D.
• Application Number:
  US10/383,115
• Publication Number:
  US 20030203881A1
• Time in Patent Office: Days
• US Class Current: 514/152
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/65 Tetracyclines
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Abstract

The invention provides a method of treating certain neurological diseases by administering to a patient in need thereof an effective amount of a tetracycline compound.

Claims

1. A method of treating or preventing a disease in a mammal comprising administering an effective amount of a tetracycline compound, the disease being Alzheimers'"'"' disease, Guillain Barré

syndrome, adreneoleukodystrophy, Parkinson'"'"'s disease, or amyotrophic lateral sclerosis.

4. The method of claim 1 wherein the tetracycline compound is a compound of formula (I)

7. The method of claim 1 wherein the tetracycline compound is minocycline or doxycycline.

9. The method of claim 1 wherein the tetracycline compound is a non-antibiotic tetracycline compound.

14. The method of claim 1 wherein the effective amount is about 0.1 mg/kg/day to about 45 mg/kg/day.

20. The method of claim 1 wherein the tetracycline compound is administered parenterally, internally or via a controlled release formulation.

21. The method of claim 1 wherein the amount is below the antibiotic effective amount.

2. A method of downregulating microglia expression in a mammal, comprising administering to the mammal in need thereof an effective amount of a tetracycline compound.

5. The method of claim 2 wherein the tetracycline compound is a compound of formula (I)

10. The method of claim 2 wherein the tetracycline is minocycline or doxycycline.

11. The method of claim 2 wherein the tetracycline is a non-antibiotic tetracycline.

15. The method of claim 10 wherein the effective amount is about 1 mg/kg/day to about 18 mg/kg/day.

3. A method of inhibiting inflammatory activity associated with microglial activation and production, comprising administering to a mammal in need thereof an effective amount of a tetracycline compound.

6. The method of claim 3 wherein the tetracycline compound is a compound of formula (I)

8. The method of claim 3 wherein the effective amount is an antiinflammatory effective amount.

12. The method of claim 3 wherein the tertracycline compound is minocycline or doxycycline.

13. The method of claim 3 wherein the tetracycline is a non-antibiotic tetracycline.

17. The method of claim 3, wherein an antiinflammatory agent is co-administered with the tetracycline compound.

18. The method of claim 12 wherein the tetracycline compound is administered over a period of time until the mammal becomes asymptomatic or the symptoms are reduced by at least 50% compared to pre-treatment symptoms.

16. A method of reducing the neurologic symptoms associated with increased expression of microglia or increased microglia cell production in a mammal, the method comprising administering an effective amount of a tetracycline compound to the mammal.

19. A pharmaceutical combination comprising a first antiinflammatory agent which is a tetracycline compound and a second antiinflammatory agent.

22. A method of treating or preventing a neurologic disease in a mammal comprising administering to the mammal suffering therefrom an effective amount of a tetracycline compound of formula (I)

23. The method of claim 22 wherein the disease is Alzheimers'"'"' disease.

24. The method of claim 22 wherein the disease is Guillain Barré

syndrome.

25. The method of claim 22 wherein the disease is adreneoleukodystrophy.

26. The method of claim 22 wherein the disease is Parkinson'"'"'s disease.

27. The method of claim 22 wherein the disease is amyotrophic lateral sclerosis.

28. The method of claim 22 wherein the amount about 0.1 mg/kg/day to about 45 mg/kg/day.

29. The method of claim 28 wherein the amount is about 0.1 mg/kg/day to about 18 mg/kg/day.

30. The method of claim 22 wherein the amount is sufficient to reduce symptoms of the disease at least 50% compared to pre-treatment symptoms.

31. The method of claim 22 wherein the administering is done for a period of about 2 to 3 weeks or until the mammal becomes asymptomatic of the disease.

32. A method of treating inflammatory conditions associated with Alzheimer'"'"'s disease, Guillain-Barré

syndrome, adrenoleukodystrophy, Parkinson'"'"'s disease and amytrophic lateral sclerosis in a subject comprising administering to the subject an effect amount of a tetracycline compound in a pharmaceutical carrier.

33. The method of claim 32 wherein the tetracycline compound is a compound of formula (I)

34. The method of claim 32 wherein the tetracycline compound is minocycline or doxycycline.

35. The method of claim 32 wherein the tetracycline compound is a non-antibiotic tetracycline compound.

36. The method of claim 32 wherein the effective amount is about 0.1 to about 45 mg/kg/day.

37. The method of claim 36 wherein the effective amount is about 1 to about 18 mg/kg/day.

38. The method of claim 32 wherein the effective amount is sufficient to reduce symptoms of the inflammatory condition at least 50% compared to pre-treatment symptoms.

39. A method of treating inflammatory conditions associated with Alzheimer'"'"'s disease, adrenoleukodystrophy, Parkinson'"'"'s disease and amytrophic lateral sclerosis in a subject comprising administering to the subject an effect amount of a tetracycline compound in a pharmaceutical carrier.

40. A method of modulating the effects of inflammatory conditions associated with Alzheimer'"'"'s disease, Guillain-Barré

syndrome, adrenoleukodystrophy, Parkinson'"'"'s disease and amytrophic lateral sclerosis in a subject comprising administering to the subject an effect amount of a tetracycline compound in a pharmaceutical carrier.

41. A combined pharmaceutical preparation, comprising a tetracycline compound of formula (I)

42. A pharmaceutical packaging comprising (i) a plurality of containers therein, at least one of the containers containing a tetracycline compound of formula (I)

43. A pharmaceutical packaging in accordance with claim 42, wherein the tetracycline is provided in a controlled release formulation.

44. A pharmaceutical packaging in accordance with claim 42, wherein the agent is an anti-inflammatory agent.

45. A pharmaceutical packaging in accordance with claim 42, wherein the agent is a free radical scavenger.

46. A pharmaceutical packaging in accordance with claim 42, further comprising both an anti-inflammatory agent and a free radical scavenger.