Methods and compositions for treating amyloid-related diseases

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...

AI Technical Summary

Benefits of technology

[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.

[0092] In one embodiment, the compounds disclosed herein prevent or inhibit amyloid protein assembly into insoluble fibrils which, in vivo, are deposited in various organs, or it favors clearance of pre-formed deposits or slows deposition in patients already having deposits. In another embodiment, the compound may also prevent the amyloid protein, in its soluble, oligomeric form or in its fibrillar form, from binding or adhering to a cell surface and causing cell damage or toxicity. In yet another embodiment, the compound may block amyloid-induced cellular toxicity or macrophage activation. In another embodiment, the compound may block amyloid-induced neurotoxicity or microglial activation. In another embodiment, the compound protects cells from amyloid induced cytotoxicity of B-islet cells. In another embodiment, the compound may enhance clearance from a specific organ, e.g., the brain or it decreases concentration of the amyloid protein in such a way that amyloid fibril formation is prevented in the targeted organ.

[0094] The compounds of the invention may be administered therapeutically or prophylactically to treat diseases associated with amyloid-β fibril formation, aggregation or deposition. The compounds of the invention may act to ameliorate the course of an amyloid-β related disease using any of the following mechanisms (this list is meant to be illustrative and not limiting): slowing the rate of amyloid-β fibril formation or deposition; lessening the degree of amyloid-β deposition; inhibiting, reducing, or preventing amyloid-β fibril formation; inhibiting neurodegeneration or cellular toxicity induced by amyloid-β; inhibiting amyloid-β induced inflammation; enhancing the clearance of amyloid-β from the brain; or favoring the degradation of amyloid-β protein prior to its organization in fibrils.

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.

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