Methods and compositions for treating amyloid-related diseases
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a technology for amyloid fibrils and compositions, applied in the direction of drug compositions, peptides, cardiovascular disorders, etc., can solve the problems of amyloid fibrils, once deposited, becoming toxic to surrounding cells, severe pain, joint stiffness and swelling,
Inactive Publication Date: 2007-01-11
BELLUS HEALTH (INT) LTD (CH)
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[0024] The present invention relates to the use of certain compounds in the treatment of amyloid-related diseases. In particular, the invention relates to a method of treating or preventing an amyloid-related disease in a subject comprising administering to the subject a therapeutic amount of a compound of the invention. The invention also pertains to each of the novel compounds of the invention as described herein. Among the compounds for use in the invention are those according to the following Formulae, such that, when administered, amyloid fibril formation, organ specific dysfunction (e.g., neurodegeneration), or cellular toxicity is reduced or inhibited.
Problems solved by technology
Once these amyloids have formed, there is no known, widely accepted therapy or treatment which significantly dissolves amyloid deposits in situ, prevents further amyloid deposition or prevents the initiation of amyloid deposition.
In specific cases, amyloid fibrils, once deposited, can become toxic to the surrounding cells.
This causes severe pains, joint stiffness and swelling.
Method used
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Binding and Antifibrillogenic Assays
[0427] The test compounds were synthesized and screened by mass spectrometry (“MS”) assays, except for selected compounds which were purchased from a commercial source. The MS assay gives data on the ability of compounds to bind to proteins, in this example, to β-amyloid and IAPP.
[0428] In the MS assay for Aβ40, samples were prepared as aqueous solutions (adding 20% ethanol if necessary to solubilize in water), 200 μM of a test compound and 20 μM of solubilized Aβ40, or 400 μM of a test compound and 40 μM of solubilized Aβ40. The pH value of each sample was adjusted to 7.4 (±0.2) by addition of 0. 1% aqueous sodium hydroxide. The solutions were 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 after sample preparation. The source temperature was kept at 70° C. and the cone voltage was 20 V for all the analysi...
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Abstract
Methods, compounds, pharmaceutical compositions and kits are described for treating or preventing amyloid-related disease.
Description
RELATED APPLICATIONS [0001] This application claims priority to U.S. Provisional Patent Application 60 / 638,819, filed on Dec. 22, 2004. This application is also a continuation-in-part of U.S. patent appplication Ser. No. 10 / 871,514, filed Jun. 18, 2004, which claims priority to U.S. patent application Ser. No. 10 / 871,365 filed Jun. 18, 2004, U.S. Provisional Patent Application No. 60 / 512,047, filed Oct. 17, 2003, and U.S. Provisional Patent Application No. 60 / 480,906, filed Jun. 23, 2003, all entitled Methods and Compositions for Treating Amyloid-Related Diseases. This application is also related to U.S. Provisional Application Serial No. 60 / 638,636, filed Dec. 22, 2004. [0002] This application is also related to U.S. Provisional Patent Application No. 60 / 512,017, filed Oct. 17, 2003, U.S. Provisional Patent Application No. 60 / 480,918, filed Jun. 23, 2003, and U.S. patent application Ser. No. 10 / 871,613, filed Jun. 18, 2004, all entitled Methods for Treating Protein Aggregation Diso...
Claims
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Application Information
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Patent Type & Authority Applications(United States)
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