Method for treating Alzheimer's disease with folic acid

• US 6,008,221 A
• Filed: 10/28/1997
• Issued: 12/28/1999
• Est. Priority Date: 11/06/1996
• Status: Expired due to Term

• Current Assignee: University of Oxford
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Smith, Anthony David, Jobst, Kim Anthony
• Primary Examiner(s): Criares, Theodore J.
• Application Number:
  US08/959,035
• Time in Patent Office: 791 Days
• Field of Search: 514/254, 514/258
• US Class Current: 514/250
• 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 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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: A61P 9/00 Drugs for disorders of the cardiovascular system

Abstract

A method is provided for treating occlusive vascular disease or Alzheimer'"'"'s disease, wherein the patient has at least moderately elevated blood levels of homocysteine and at least moderately reduced blood levels of folate and vitamin B₁₂, wherein the patient is treated with folic acid, a folate or a derivative thereof, and optionally vitamin B₁₂, and optionally an organic nitrate such as isosorbide mononitrate or dinitrate, or an ACE inhibitor or an angiotensin II antagonist, or a NEP/ACE inhibitor or a combination of two or more of the above.

Claims

1. A method for treating Alzheimer'"'"'s disease or inhibiting microvascular events leading to neurodegeneration, which comprises administering to a patient in need of treatment a therapeutically effective amount of a drug which causes a reduction in at least moderately elevated blood levels of homocysteine or modifies the toxic effects of at least moderately elevated blood levels of homocysteine on the vasculature or on nerve cells in the brain, wherein said drug comprises folic acid or a folate or a derivative thereof, with the proviso that the drug is exclusive of coenzyme Q10.

2. A method for treating Alzheimer'"'"'s disease, which comprises administering to a patient in need of treatment a therapeutically effective amount of a drug which causes a reduction in at least moderately elevated blood levels of homocysteine or modifies the toxic effects of at least moderately elevated blood levels of homocysteine on the vasculature or on nerve cells in the brain, wherein said drug comprises folic acid or a folate or a derivative thereof, with the proviso that the drug is exclusive of coenzyme Q10.

3. The method as defined in claim 2 wherein the patient has at least moderately elevated blood levels of homocysteine and at least moderately reduced blood levels of folate and vitamin B₁₂.

4. The method as defined in claim 2 wherein the drug administered is folic acid or a folate or a derivative thereof or a combination of two or more thereof.

5. The method as defined in claim 4 wherein the drug is folic acid (pteroylmonoglutamate), one or more of the folylpolyglutamates, compounds in which the pyrazine ring of the pterin moiety of folic acid or of the folylpolyglutamates is reduced to give dihydrofolates or tetrahydrofolates, or derivatives of all the preceding compounds in which the N-5 or N-10 positions carry one carbon units at various levels of oxidation, or a combination of two or more thereof.

6. The method as defined in claim 5 wherein the drug is

folic acid,

dihydrofolate,

tetrahydrofolate,

5-methyltetrahydrofolate,

5,10-methylenetetrahydrofolate,

5,10-methenyltetrahydrofolate,

5,10-formiminotetrahydrofolate,

5-formyltetrahydrofolate (leucovorin),

10-formyltetrahydrofolate, or a combination of two or more thereof.

7. The method as defined in claim 3 further including the step of administering vitamin B₁₂.

8. The method as defined in claim 2 wherein folic acid, folate or a derivative thereof is administered in a daily dosage within the range from about 0.1 to about 100 mg.

9. The method as defined in claim 7 wherein vitamin B₁₂ is administered in a daily dosage within the range from about 0.001 to about 10 mg.

10. The method as defined in claim 2 further including administering a drug for treating Alzheimer'"'"'s disease which is a cholinesterase inhibitor, a muscarinic receptor agonist, an inhibitor of β

-amyloid production, an inhibitor of neurofibrillary tangle formation or a combination of two or more thereof.

11. A method for inhibiting microvascular events leading to Alzheimer'"'"'s disease, which comprises administering to a patient in need of treatment a therapeutically effective amount of a drug which causes a reduction in at least moderately elevated blood levels of homocysteine or modifies the toxic effects of at least moderately elevated blood levels of homocysteine on the vasculature or on nerve cells in the brain, wherein said drug comprises folic acid, a folate or a derivative thereof, with the proviso that the drug is exclusive of coenzyme Q10.

12. The method as defined in claim 11 wherein the patient has at least moderately elevated blood levels of homocysteine and at least moderately reduced blood levels of folate and vitamin B₁₂.

13. The method as defined in claim 11 wherein the drug administered is folic acid or a folate or a derivative thereof or betaine or vitamin B₆ or a combination of two or more thereof.

14. The method as defined in claim 13 wherein the drug is folic acid (pteroylmonoglutamate), one or more of the folylpolyglutamates, compounds in which the pyrazine ring of the pterin moiety of folic acid or of the folylpolyglutamates is reduced to give dihydrofolates or tetrahydrofolates, or derivatives of all the preceding compounds in which the N-5 or N-10 positions carry one carbon unit at various levels of oxidation, or a combination of two or more thereof.

15. The method as defined in claim 14 wherein the drug is

folic acid,

dihydrofolate,

tetrahydrofolate,

5-methyltetrahydrofolate,

5,10-methylenetetrahydrofolate,

5,10-methenyltetrahydrofolate,

5,10-formiminotetrahydrofolate,

5-formyltetrahydrofolate (leucovorin),

10-formyltetrahydrofolate, or a combination of two or more thereof.

16. The method as defined in claim 11 wherein folic acid, folate or a derivative thereof is administered in a daily dosage within the range from about 0.1 to about 100 mg.