Method for reducing amyloid deposition, amyloid neurotoxicity and microgliosis

• US 7,732,467 B2
• Filed: 05/17/2004
• Issued: 06/08/2010
• Est. Priority Date: 05/15/2003
• Status: Active Grant

• Current Assignee: Alzheimer's Institute Of America
• Original Assignee: Alzheimer's Institute Of America
• Inventors: Paris, Daniel, Mullan, Michael J.
• Primary Examiner(s): Kim; Jennifer M
• Application Number:
  US10/847,630
• Publication Number:
  US 20050009885A1
• Time in Patent Office: 2,213 Days
• Field of Search: 514/355
• US Class Current: 514/355
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention provides methods for reducing β-amyloid deposition, β-amyloid neurotoxicity and microgliosis in animals or humans afflicted with a cerebral amyloidogenic disease, such as Alzheimer'"'"'s disease (AD), by administering therapeutically effective amounts of the dihydropyridine calcium channel antagonist, nilvadipine. The present invention also provides methods for diagnosing cerebral amyloidogenic diseases in animals or humans. Further provided are methods for reducing the risk of β-amyloid deposition, β-amyloid neurotoxicity and microgliosis in animals or humans suffering from traumatic brain injury by administering nilvadipine immediately after the traumatic brain injury and continuing treatment for a prescribed period of time thereafter. Finally, methods are provided for treating transplantable neuronal stem cells by administering nilvadipine to the neuronal stem cells prior to transplantation in the central nervous system of an animal or human afflicted with a cerebral amyloidogenic disease, such as AD.

Claims

1. A method for reducing β

-amyloid deposition, β

-amyloid neurotoxicity and microgliosis in animals and humans afflicted with Alzheimer'"'"'s disease, consisting essentially of the administration of nilvadipine to the animal or human.

2. The method of claim 1, wherein the amount of nilvadipine administered is between about 0.05-20 mg per day.

3. The method of claim 1, wherein the amount of nilvadipine administered is between about 2-15 mg per day.

4. The method of claim 1, wherein the amount of nilvadipine administered is between about 4-12 mg per day.

5. The method of claim 1, wherein the amount of nilvadipine administered is 8 mg per day.

6. The method of claim 1, wherein the duration of nilvadipine treatment lasts for up to the lifetime of the animal or human.

7. The method of claim 1, wherein the administration of nilvadipine to the animal or human is via parenteral, oral or intraperitoneal administration.

8. The method of claim 7, wherein the administration is oral administration that is in the form of hard or soft shell gelatin capsules, tablets, troches, sachets, lozenges, elixirs, suspensions, syrups, wafers, powders, granules, solutions or emulsions.

9. The method of claim 7, wherein the administration is oral administration that is in the form of a sustained release formulation.

11. The method of claim 1, wherein said administration is chronic administration.

12. The method of claim 1, wherein said method is for use in humans.

10. A method for reducing β

-amyloid deposition, β

-amyloid neurotoxicity and microgliosis in animals or humans afflicted with Alzheimer'"'"'s disease consisting essentially of administering to the animal or human a pharmaceutical composition consisting of a therapeutically effective amount of nilvadipine and a pharmaceutically acceptable carrier.