Compounds for treating alzheimer's disease and for inhibiting beta-amyloid peptitde production

A technology for Alzheimer's and amyloid, which is applied in the field of compounds used to treat Alzheimer's disease and inhibit the production of amyloid beta peptide, and can solve problems such as side effects

Inactive Publication Date: 2008-02-27
THE TRUSTEES OF COLUMBIA UNIV IN THE CITY OF NEW YORK
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Therefore, the complete inhibition of γ-secretase activity will likely lead to serious side effects (Deorfler et al., Links Free inPMC Presenilin-dependent gamma-secretase activity modulates thymocyte development. (2001) Proc.Natl.Acad.Sci.USA 98,9312-9317; Hadland et al., Gamma-secretase inhibitors repress thymocytedevelopment. Proc. Natl. Acad. Sci. USA 98, 7487-7491)

Method used

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  • Compounds for treating alzheimer's disease and for inhibiting beta-amyloid peptitde production
  • Compounds for treating alzheimer's disease and for inhibiting beta-amyloid peptitde production
  • Compounds for treating alzheimer's disease and for inhibiting beta-amyloid peptitde production

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Embodiment 1

[0092] To detect the possible role of ginsenosides and their analogues in the treatment of AD. First, various ginsenosides were screened based on their effects on Aβ production. Chinese hamster ovary (CHO) cells expressing human APP (CHO-APP cells) were cultured with each ginsenoside purified from untreated ginseng (called white ginseng), and the effects of various ginsenosides on Aβ ( Such as the impact of Aβ40 and Aβ42) generation. These representative ginsenosides include Rb1, Rb2, Rc, Rd, Re, Re, Rg1 and Rg2, which differ in their side chains and sugar groups.

[0093]Tables 1-3 Structures of ginsenosides used in the studies and their effects on Aβ42 production. They differ by two or three side chains attached to a common triterpene backbone called dammaranes. The common structural skeleton of each group of ginsenosides is shown in the upper figure. Ginsenosides with Aβ42-lowering activity are indicated in the rightmost column of the table: reduced Aβ42 activity ("Yes"...

Embodiment 2

[0109] The therapeutic benefit of ginsenosides for the treatment of AD-associated neurodegeneration can be demonstrated in murine AD models. Specifically, ginsenoside compounds (20S) Rg3, Rk1, Rg5, and Rgk351 can be used to treat mice with AD-related neurodegeneration.

[0110] Mice expressing human APP as well as mice expressing the Swedish familial AD mutant form of APP were obtained from Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609. Four groups of mice can then be studied: (1) APP mice, not treated with ginsenoside (placebo); (2) Swedish mice, not treated with ginsenoside (placebo); (3) APP mice+Rg5 (100 μg / μl / day); and (4) Swedish mice+Rg5 (100 μg / μl / day). After approximately 16 weeks of injection treatment, the amount of A[beta]42 in the serum of the mice was determined. The results of this study are expected to demonstrate the general benefit of ginsenoside treatment for the treatment of AD-related neurodegeneration. Compared with APP mice and Swedish...

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Abstract

The present invention provides compositions and methods for treating and preventing Alzheimer's disease by administering to a subject an effective amount of a dammarane or ginsenoside compound. The invention also provides compositions and methods for modulating beta-amyloid protein production, including Abeta42 in a cell. The invention further provides compositions and methods for treating and preventing neurodegeneration by administering to a subject an effective amount of a dammarane or ginsenoside compound. Additionally, the invention provides kits for use in treating and / or preventing Alzheimer's disease and neurodegeneration, as well as for reducing the production of beta-amyloid protein.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to US nonprovisional application 10 / 834,773, filed April 28, 2004, which is incorporated herein by reference. [0003] Statement of Government Interest [0004] This invention was supported in part by Government NIH grant RO1 NS 43467. Accordingly, the US Government may have certain rights in this invention. Background of the invention [0005] Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive, irresistible loss of cognitive function (Francis et al., Neuregulins and ErbB receptors incultured neonatal astrocytes. J Neurosci. Res., 57: 487 -94, 1999), culminating in an inability to maintain normal social and / or occupational behavior. Alzheimer's disease is the most common type of age-related dementia and the most serious health problem in the United States. About 4 million Americans live with Alzheimer's disease, which costs at least $100 billion a yea...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07J9/00A61K31/56A61K31/57A61K31/704C07H15/24C07J17/00
CPCC07H15/24C07J17/00A61P25/28A61P43/00A61K31/704
Inventor 金泰万钟胜权
Owner THE TRUSTEES OF COLUMBIA UNIV IN THE CITY OF NEW YORK
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