Treatment of MCI and Alzheimer's disease

A composition and drug technology, applied in the direction of botanical equipment and methods, pharmaceutical formulations, medical preparations containing active ingredients, etc., can solve problems such as neurodegeneration that does not show

Inactive Publication Date: 2013-03-20
UNIV OF KENTUCKY RES FOUND
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Moreover, Dr. Eschenbach noted that none of the five approved drugs has been

Method used

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  • Treatment of MCI and Alzheimer's disease
  • Treatment of MCI and Alzheimer's disease
  • Treatment of MCI and Alzheimer's disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0253] Example 1: Neurotoxicity of the PDS / TTR complex

[0254] Examination of the cell culture medium of epithelial cells from Alzheimer's patients showed elevated levels of the PDS / TTR complex compared with control cells, suggesting that the PDS / TTR complex could act as a An effective biomarker for the early diagnosis of MM. See US Patent Application Publication No. 20080026405, the disclosure of which is incorporated herein by reference. This example shows that the PDS / TTR complex is neurotoxic in addition to being a biomarker of disease.

[0255] First, it was found that acrolein (a by-product of lipid peroxidation, α,β-unsaturated tricarbonaldehyde) caused normal control epithelial cells to express PDS / TTR complexes in the medium at levels comparable to those from Alzheimer's The epithelial cells of patients with Mersen's disease are comparable. In these experiments, primary cultures of choroidal plexus epithelial cells were established rapidly after necropsy using e...

Embodiment 2

[0260] Example 2: Inhibition of PDS / TTR Expression by Nifedipine, Nifedipine Analog Mixture and / or T3 / T4

[0261]The assay described in Example 1 provides a tool for identifying potential therapeutic agents capable of protecting neuronal cells against the PDS / TTR complex. The inventors observed that compounds such as nifedipine (1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylate, CAS# 21829-25-4 (Sigma Aldrich)), a calcium channel blocker for the treatment of hypertension; or nifedipine analogues such as oxidized derivatives of nifedipine (2,6-dimethyl-4-(2 -nitrophenyl)-3,5-pyridinedicarboxylate, CAS#67035-22-7 (Sigma Aldrich)) or nitroso derivatives of nifedipine (2,6-dimethyl- Dimethyl 4-(2-nitrosophenyl)-3,5-pyridinedicarboxylate, CAS#50428-14-3 (Sigma Aldrich)), alone or in combination, potently inhibits Expression of the PDS / TTR complex. In addition, T3 and T4 were evaluated and found to be effective in inhibiting the expression of the PDS / TTR comp...

Embodiment 3

[0266] Example 3: Nifedipine analogs inhibit the production of inflammatory cytokines

[0267] It has been reported that inflammatory response elements (cytokines) are increased in Alzheimer's patients. The present inventors tested the nifedipine mixture and its respective analogues in astrocytoma cultures. Human astrocytoma cells were 2.5X 10 5 Cells / well were seeded in 6-well culture plates and cultured for 24 hours. The cultures were then changed to serum-free selective MEM medium and treated with a mixture of nifedipine and its respective analogs for 24 hours. Three 6-well plates were used per treatment. After treatment, the medium in each well was collected and the levels of IL-1β, IL-6, TNF-α and TGF-β were detected using commercial ELISA. For example results see Figure 7 . Such as Figure 7 As shown, the levels of secreted IL-1, IL-6, and TNF-α in the medium were significantly decreased after treatment with the nifedipine mixture or oxidized nifedipine, sugges...

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Abstract

The present invention provides, among other things, therapeutic compositions and methods that can effectively treat, slow or prevent a neurological disease (e.g., a neurodegenerative disease, e.g., mild cognitive impairment (MCI) or Alzheimer's disease (AD)), in particular, based on therapeutically effective amount of nifedipine, oxidized or nitroso nifedipine derivatives, lactam (e.g., a compound of formula (Ic) or (Ic-i), e.g., NFD- L1), thyroxine (T4), triiodothyronine (T3) and combinations thereof.

Description

Background of the invention [0001] Alzheimer's disease (AD) is a well-known but still understudied progressive neurodegenerative disease that affects an increasing number of individuals in the aging population. Alzheimer's disease currently affects four million Americans. Statistics from the National Institute on Aging show that 14 million Americans could develop Alzheimer's disease by 2040 unless prevention strategies are found. [0002] The earliest clinical symptoms of Alzheimer's disease are described as symptoms called mild cognitive impairment (MCI). Although detection of MCI may allow necessary lifestyle modifications to be planned and implemented, there is currently no therapy to prevent MCI from developing into Alzheimer's or to treat Alzheimer's. [0003] As early as 2007, Dr. Andrew C. von Eschenbach, an official of the U.S. Senate and FDA, predicted that "the current 4.5 million Alzheimer's disease cases are expected to increase to about 16 million by 2050." Dr....

Claims

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Application Information

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IPC IPC(8): A01N43/40
CPCA61K31/44A61K31/4422A61P25/28A61P43/00A61K2300/00
Inventor M·洛弗尔B·林恩
Owner UNIV OF KENTUCKY RES FOUND
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