Therapeutic formulations for the treatment of beta-amyloid related diseases

A technology of amyloid, therapeutic agent, applied in nervous system diseases, peptide/protein components, medical preparations containing active ingredients, etc.

Inactive Publication Date: 2006-03-29
NEUROCHEM INT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Once these amyloid deposits have formed, no widely accepted treatment

Method used

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  • Therapeutic formulations for the treatment of beta-amyloid related diseases
  • Therapeutic formulations for the treatment of beta-amyloid related diseases
  • Therapeutic formulations for the treatment of beta-amyloid related diseases

Examples

Experimental program
Comparison scheme
Effect test

specific example

[0309] Specific examples of peptides described in WO 02 / 096937 A2 that can be used in the present invention include the following:

[0310] Aβ(1-42, all-D)DAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIA,

[0311] Aβ(1-40, all-D)DAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVV,

[0312] Aβ(1-35, all-D)DAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLM,

[0313] Aβ(1-28, all-D)DAEFRHDSGYEVHHQKLVFFAEDVGSNK,

[0314] Aβ(1-7, all-D)DAEFRHD,

[0315] Aβ(10-16, all-D)YEVHHQK,

[0316] Aβ(16-21, all-D)KLVFFA,

[0317] Aβ(10-21, all-D)YEVHHQKLVFFA,

[0318] Aβ(13-21, all-D)HHQKLVFFA,

[0319] Aβ(36-42, all-D)VGGVVIA, and

[0320] Lys-Ile-Val-Phe-Phe-Ala (all-D); Lys-Lys-Leu-Val-Phe-Phe-Ala (all-D);

[0321] Lys-Phe-Val-Phe-Phe-Ala (all-D); Ala-Phe-Phe-Val-Leu-Lys (all-D); Lys-Leu-Val-Phe (all-D);

[0322] Lys-Ala-Val-Phe-Phe-Ala (all-D); Lys-Leu-Val-Phe-Phe (all-D); Lys-Leu-Val-Phe-Phe-Ala-NH 2 (All-D); Lys-Ile-Val-Phe-Phe-Ala-NH 2 (All-D); Lys-Leu-Val-Phe-Phe-Ala-NH 2 (full-D);

[0323] Lys-Phe-Val-...

Embodiment

[0653] Binding and Antigen Fibril Formation Tests

[0654] Test compounds were purchased from commercial sources or synthesized or screened by mass spectrometry ("MS") analysis. MS analysis gives data on the ability of the compound to bind amyloid.

[0655] In mass spectrometry ("MS") analysis, samples were prepared as aqueous solutions containing 20% ​​ethanol, 200 [mu]M test compound and 20 [mu]M dissolved A[beta]40. The pH of each sample was adjusted to 7.4 (±0.2) by adding 0.1% aqueous sodium hydroxide. The solution was then analyzed by electrospray ionization mass spectrometry using a Waters ZQ 4000 mass spectrometer. Samples were introduced by direct infusion at a flow rate of 25 μL / min within 2 hours of sample preparation. The source temperature was maintained at 70°C and the pore voltage was 20V for all analyses. Data were processed using Masslynx 3.5 software. The MS test gives data on the ability of the compound to bind soluble A[beta], while the ThT, EM and CD ...

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Abstract

A method of preventing or treating an amyloid-β-related disease in an individual, the method comprising administering to an individual in need thereof an effective amount of a first therapeutic agent for preventing or treating an amyloid-β-related disease, and a second A therapeutic agent, the second therapeutic agent being (i) a peptide or peptidomimetic compound that modulates amyloid-beta fibril formation or induces a prophylactic or therapeutic immune response against amyloid-beta fibril formation, or (ii) Immune system modulator that prevents or inhibits amyloid-beta fibril formation.

Description

Background of the invention [0001] Alzheimer's disease is a destructive disease of the brain that results in progressive memory loss leading to dementia, physical incapacity and over an extended period of time death. As populations in developed countries age, the number of Alzheimer's patients is reaching epidemic proportions. [0002] Alzheimer's disease patients develop progressive dementia in adults with 3 main structural changes in the brain: diffuse loss of neurons in multiple parts of the brain; intracellular protein deposits called neurofibrillary junctions and accumulation of extracellular protein deposits called amyloid or senile plaques surrounding malformed nerve terminals (dystrophic axons). The major component of these amyloid plaques is the amyloid-beta peptide (Aβ), a protein of 39-43 amino acids produced by the cleavage of the β-amyloid precursor protein (APP) . The relevance of A[beta] deposits in Alzheimer's disease has been well studied (see eg Selkoe, Tr...

Claims

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Application Information

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IPC IPC(8): A61K31/185A61K38/00A61P25/28
Inventor F·热尔韦斯F·贝利尼
Owner NEUROCHEM INT
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