US2019105341A1PendingUtilityA1

Compositions and Methods for Treating Alzheimer's Disease and Other Tauopathies

63
Assignee: UNIV LELAND STANFORD JUNIORPriority: Mar 15, 2013Filed: Dec 11, 2018Published: Apr 11, 2019
Est. expiryMar 15, 2033(~6.6 yrs left)· nominal 20-yr term from priority
Inventors:Bingwei LuSeongsoo Lee
C12N 2310/14A61K 31/713A61K 48/005C12N 15/113A61K 31/44C12N 2320/30A61K 48/00A61K 45/06C12N 2310/141C12N 15/1137C12Y 304/19012
63
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Claims

Abstract

Compounds, pharmaceutical compositions, and methods of using such compounds and compositions to treat or prevent Alzheimer's disease and related tauopathies through the inhibition of USP-9X and/or enhancement of SCF(β-TrCP).

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A method for preventing or treating tauopathies in an animal, the method comprising administering to the animal an effective amount of a composition comprising a USP-9x inhibitor and a pharmaceutically acceptable carrier thereof. 
     
     
         2 . The method of  claim 1 , wherein the USP-9x inhibitor is WP1130 or derivatives thereof. 
     
     
         3 . The method of  claim 1 , wherein the USP-9x inhibitor is RNAi, miRNA, or shRNA targeting USP-9x. 
     
     
         4 . The method of  claim 1  further comprising administering a SCF(β-TrCP) enhancer. 
     
     
         5 . The method of  claim 4  wherein the SCF(β-TrCP) enhancer increases the neddylation of Cullin. 
     
     
         6 . The method of  claim 4 , wherein the SCF(β-TrCP) enhancer increases the expression or activity of NEDD8 or NAE. 
     
     
         7 . The method of  claim 4 , wherein the SCF(β-TrCP) enhancer is a gene therapy that increases expression of NEDD8 or NAE. 
     
     
         8 . The method of  claim 4 , wherein the SCF(β-TrCP) enhancer is a small molecule activator of NAE. 
     
     
         9 . The method of  claim 4 , wherein the SCF(β-TrCP) enhancer increases activity and/or expression of CAND1. 
     
     
         10 . The method of  claim 4 , wherein the SCF(β-TrCP) enhancer increases expression of CAND1 by a gene therapy. 
     
     
         11 . The method of  claim 4 , wherein the SCF(β-TrCP) enhancer increases activity of CAND1 through administration of a small molecule activator of CAND1. 
     
     
         12 . The method of  claim 4 , wherein the SCF(β-TrCP) enhancer decreases Cullin deneddylation. 
     
     
         13 . The method of  claim 4 , wherein the SCF(β-TrCP) enhancer inhibits CSN. 
     
     
         14 . The method of  claim 4 , wherein the SCF(β-TrCP) enhancer is RNAi targeting CSN. 
     
     
         15 . The method of  claim 1 , wherein the inhibitor is present in a therapeutically effective amount. 
     
     
         16 . The method of  claim 1 , wherein the inhibitor is present in a prophylactically effective amount. 
     
     
         17 . The method of  claim 1 , wherein the animal is a human. 
     
     
         18 . The method of  claim 17  wherein the human is at elevated risk of developing Alzheimer's disease. 
     
     
         19 . The method of  claim 18 , wherein the human is a carrier of a mutation in one or more of presenilin 1, presenilin 2, or amyloid precursor protein (APP). 
     
     
         20 . The method of  claim 17 , wherein the method stimulates the degradation of activated MARK.

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