Baclofen and acamprosate based therapy of neurological disorders
The present invention relates to combinations and methods for the treatment of neurological disorders related to glutamate excitotoxicity and Amyloid β toxicity. More specifically, the present invention relates to novel combinatorial therapies of Alzheimer's disease, Alzheimer's disease related disorders, amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Huntington's disease, neuropathic pain, alcoholic neuropathy, alcoholism or alcohol withdrawal, or spinal cord injury, based on baclofen and acamprosate combination.
1. A method of treating Alzheimer's disease or a related disease selected from senile dementia of AD type (SDAT), frontotemporal dementia (FTD), mild cognitive impairment (MCI) and age-associated memory impairment (AAMI), comprising administering twice daily to a subject in need thereof from 0.4 to 50 mg of acamprosate and from 6 to 15 mg of baclofen, or pharmaceutically acceptable salts thereof.
2. The method of claim 1 , wherein baclofen and acamprosate compounds are mixed with a pharmaceutically acceptable carrier or excipient.
3. The method of claim 1 , wherein baclofen and acamprosate are formulated or administered together, separately or sequentially.
4. The method of claim 1 , wherein baclofen and acamprosate are administered repeatedly to the subject.
5. The method of claim 1 , wherein baclofen and acamprosate are administered in an amount effective to protect neuronal and endothelial functions from Aβ toxicity.
6. The method of claim 1 , comprising administering 1 mg acamprosate and 15 mg baclofen, twice daily.
7. The method of claim 1 , comprising administering 20 mg acamprosate and 12 mg baclofen, twice daily.
8. The method of claim 1 , comprising administering 40 mg acamprosate and 12 mg baclofen, twice daily.
9. The method of claim 1 , further comprising administering donepezil, galantamine, rivastigmine, or memantine or pharmaceutically acceptable salts thereof.
10. The method of claim 1 , further comprising administering 0.6 mg donepezil, twice daily.
11. The method of claim 1 , comprising administering 20 mg acamprosate, 12 mg baclofen and 0.6 mg donepezil, twice daily.
12. The method of claim 1 , comprising administering 40 mg acamprosate, 12 mg baclofen and 0.6 mg donepezil, twice daily.
13. The method of claim 1 , wherein the subject is a human subject.
14. The method of claim 1 , wherein the subject is a human subject suffering from AD.
15. The method of claim 1 , wherein the subject is a human subject suffering from AAMI.
16. The method of claim 1 , wherein the subject is a human subject suffering from FTD.
17. A method for correcting or treating cognitive impairment in a subject suffering from Alzheimer's disease, the method comprising administering twice daily to said subject from 0.4 to 50 mg of acamprosate and from 6 to 15 mg of baclofen, or pharmaceutically acceptable salts thereof.
18. A method for correcting or treating memory impairment in a subject suffering from Alzheimer's disease, the method comprising administering twice daily to said subject from 0.4 to 50 mg of acamprosate and from 6 to 15 mg of baclofen, or pharmaceutically acceptable salts thereof.
19. The method of claim 17 , wherein baclofen and acamprosate compounds are mixed with a pharmaceutically acceptable carrier or excipient.
20. The method of claim 17 , wherein baclofen and acamprosate are formulated or administered together, separately or sequentially.
21. The method of claim 17 , wherein baclofen and acamprosate are administered repeatedly to the subject.
22. The method of claim 17 , wherein baclofen and acamprosate are administered in an amount effective to protect neuronal and endothelial functions from Aβ toxicity.
23. The method of claim 17 , comprising administering 1 mg acamprosate and 15 mg baclofen, twice daily.
24. The method of claim 17 , comprising administering 20 mg acamprosate and 12 mg baclofen, twice daily.
25. The method of claim 17 , comprising administering 40 mg acamprosate and 12 mg baclofen, twice daily.
26. The method of claim 17 , further comprising administering donepezil, galantamine, rivastigmine, or memantine or pharmaceutically acceptable salts thereof.
27. The method of claim 17 , further comprising administering 0.6 mg donepezil, twice daily.
28. The method of claim 17 , comprising administering 20 mg acamprosate, 12 mg baclofen and 0.6 mg donepezil, twice daily.
29. The method of claim 17 , comprising administering 40 mg acamprosate, 12 mg baclofen and 0.6 mg donepezil, twice daily.
30. The method of claim 17 , wherein the subject is a human subject.
31. The method of claim 18 , wherein baclofen and acamprosate compounds are mixed with a pharmaceutically acceptable carrier or excipient.
32. The method of claim 18 , wherein baclofen and acamprosate are formulated or administered together, separately or sequentially.
33. The method of claim 18 , wherein baclofen and acamprosate are administered repeatedly to the subject.
34. The method of claim 18 , wherein baclofen and acamprosate are administered in an amount effective to protect neuronal and endothelial functions from Aβ toxicity.
35. The method of claim 18 , comprising administering 1 mg acamprosate and 15 mg baclofen, twice daily.
36. The method of claim 18 , comprising administering 20 mg acamprosate and 12 mg baclofen, twice daily.
37. The method of claim 18 , comprising administering 40 mg acamprosate and 12 mg baclofen, twice daily.
38. The method of claim 18 , further comprising administering donepezil, galantamine, rivastigmine, or memantine or pharmaceutically acceptable salts thereof.
39. The method of claim 18 , further comprising administering 0.6 mg donepezil, twice daily.
40. The method of claim 18 , comprising administering 20 mg acamprosate, 12 mg baclofen and 0.6 mg donepezil, twice daily.
41. The method of claim 18 , comprising administering 40 mg acamprosate, 12 mg baclofen and 0.6 mg donepezil, twice daily.
42. The method of claim 18 , wherein the subject is a human subject.