US10258623B2 – April 16, 2019 – Compositions and methods for reduction of amyloid-beta load

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Inventors :

J. Gregor Sutcliffe; Brian S. Hilbush

Owner :

MODGENE, LLC

Application Number :

US15634593

Document Number :

US10258623B2

Priority Date :

June 27, 2017

Filing Date :

June 27, 2017

Date of Grant/ Publication :

April 16, 2019

Class :

; A61K31 / 506; A61K45 / 06

Abstract

The present invention relates to methods and compositions for modulating levels of amyloid-β peptide (Aβ) exhibited by non-neuronal (i.e., peripheral) cells, fluids, or tissues. The invention also relates to modulation of Aβ levels via selective modulation (e.g., inhibition) of γ-secretase activity. The invention also relates to methods of preventing, treating or ameliorating the symptoms of a disorder, including but not limited to an Aβ-related disorder, by administering a compound that results in the modulation of γ-secretase in a non-neuronal tissue, either directly or indirectly to prevent, treat or ameliorate the symptoms of a brain Aβ disorder, such as Alzheimer’s disease.

Claim(s)

1. A method of treating a subject having a brain Aβ disorder or predisposition to a brain Aβ disorder, comprising peripherally administering a compound that modulates production of Aβ in a peripheral tissue, wherein said compound is an imatinib derivative displaying reduced protein kinase inhibition compared to imatinib, wherein the compound is N-desmethyl imatinib or imatinib para-diaminomethylbenzene or a mixture of N-desmethyl imatinib and imatinib para-diaminomethylbenzene.;
7. A method, comprising: a) assessing a subject for the presence of a brain Aβ disorder or predisposition to a brain Aβ disorder; b) peripherally administering a compound that modulates production of Aβ, wherein said compound does not substantially penetrate the blood brain barrier, wherein said compound is imatinib para-diaminomethylbenzene, or is N-desmethyl imatinib, or is a mixture of imatinib para-diaminomethylbenzene and N-desmethyl imatinib; and; c) after said administering of step b), assessing said subject for a brain Aβ disorder or progression of a brain Aβ disorder.

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