Methods and compositions for treating amyloid-related diseases

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,

US20070010573A1Inactive Publication Date: 2007-01-11BELLUS HEALTH (INT) LTD (CH)
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Patent Information

Authority / Receiving Office
US · United States
Patent Type
Applications(United States)
Current Assignee / Owner
Publication Date
2007-01-11
Estimated Expiration
Not applicable · inactive patent

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Abstract

Methods, compounds, pharmaceutical compositions and kits are described for treating or preventing amyloid-related disease.
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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...

Examples

examples

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...