Methods for the treatment of A-β related disorders and compositions therefor

摘要

The invention provides methods for treating Aβ peptide related disorders such as Alzheimer's disease comprising administering a therapeutically effective amount of a CK1 modulator to a patient in need thereof.

主权项

1. A method to identify a candidate modulator which reduces the accumulation of Aβ peptide levels in the brain, wherein the accumulation of Aβ peptide levels is reduced as compared to a control modulator, comprising assaying for the ability of a candidate modulator to inhibit Casein Kinase 1 (“CK1”) activity by:
a) providing a biological sample comprising or expressing a CK1 polypeptide; b) contacting said biological sample with a candidate modulator and measuring the phosphorylation activity and/or gene expression of CK1 in the biological sample after the sample has been contacted with the candidate modulator; c) contacting said biological sample with a control modulator wherein the control modulator is known to modulate the activity of CK1 and/or gene expression of CK1, and measuring the phosphorylation activity and/or gene expression of CK1 in the biological sample after the sample has been contacted with the control modulator; d) comparing CK1 phosphorylation activity and/or gene expression between the candidate and control modulators; e) selecting a candidate modulator for further testing based upon its ability to decrease the phosphorylation activity of CK1 and/or gene expression of CK1, and wherein the candidate modulator decreases the phosphorylation activity and/or gene expression of CK1 relative to the control modulator; f) testing the candidate modulator in an animal model of an Aβ related disorder, wherein the candidate modulator is administered in said animal model and CK1phosphorylation activity and/or gene expression in the brain is measured after administration and compared to a control modulator in an animal model of an Aβ related disorder; and g) identifying a candidate modulator based upon its ability to decrease CK1phosphorylation activity and/or gene expression and reduce the accumulation of AB peptide in the brain of in the animal model.