IP Library Patent Application 13758796
Patent Application
App. No. 13/758,796

SUPPRESSION OF GLIAL FIBRILLARY ACIDIC PROTEIN

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Patent No.
US None
App. No.
13/758,796
Abstract

Provided herein are methods of decreasing glial fibrillary acidic protein (GFAP) levels in a cell. Such methods include administering an effective amount of a GFAP lowering compound to the cell. Also provided are compounds useful for the treatment of Alexander disease in subjects at risk of or diagnosed with Alexander disease and methods for the identification of such compounds.

Claims (27)

1 . A method of decreasing glial fibrillary acidic protein (GFAP) levels in a cell comprising:

administering an effective amount of GFAP lowering compound to the cell;

wherein the GFAP lowering compound is selected from the group consisting of c-pendant amino tricyclic compounds; quinone compounds; triterpene derivatives; and polyphenol compounds.

2 . The method of claim 1 wherein the GFAP lowering compound exhibits an hGFAP promoter luciferase reduction of at least about 10%.

3 . The method of claim 1 wherein the GFAP lowering compound exhibits a cell-based GFAP protein level reduction of at least about 6%.

4 . The method of claim 1 wherein the GFAP lowering compound has an MTDcc of at least about 10 μM.

5 . The method of claim 1 , wherein the GFAP lowering compound comprises clomiprimine.

6 . The method of claim 1 , wherein the GFAP lowering compound comprises betulinic acid and/or a betulinic acid derivative.

7 . The method of claim 1 , wherein the GFAP lowering compound comprises epigallocatechin 3,5-digallate (EGCDG).

8 . The method of claim 1 , wherein the GFAP lowering compound comprises amitriptyline.

9 . The method of claim 1 , wherein the cell is in a human subject.

10 . The method of claim 1 , wherein the GFAP lowering compound is selected from the group consisting of diaziquone, clomipramine, chrysophanol, amitriptyline, chlorprothixene, EGCDG, tamoxifen, mundoserone, amlodipine, embelin, thioridazine, ritanserin, irigenol, fluccinonide, hexetidine, estradiol benzoate, ketotifen, clobetasol propionate, colecalciferol, fluphenazine, pyrogallin, kanamycin and mixtures thereof.

11 . The method of claim 1 , wherein the GFAP lowering compound is selected from the group consisting of diaziquone, clomipramine, chrysophanol, amitriptyline, tamoxifen, amlodipine, embelin, thioridazine, ritanserin, ketotifen, kanamycin, 4-acetamidophenyl salicylate, terfenadine and mixtures thereof.

12 . The method of claim 1 , wherein the GFAP lowering compound is selected from the group consisting of diaziquone, clomipramine, chrysophanol, amitriptyline, chlorprothixene, EGCDG, mundoserone, amlodipine, ritanserin, irigenol, fluccinonide, hexetidine, estradiol benzoate, ketotifin, clobetasol propionate, colecalciferol, pyrogallin, kanamycin, azinphos methyl, 4-acetamidophenyl salicylate, oxotremorine, ritodrine, NPPB, chloramphenicol, phosphocreatine, betulinic acid, betulinic acid derivatives, methylnorlichexanthone, coumophos and mixtures thereof.

13 . A method for decreasing the amount of GFAP in a subject comprising:

administering a therapeutically effective amount of a GFAP lowering compound to the subject.

14 . The method of claim 13 , wherein the subject is a human subject.

15 . The method of claim 13 , wherein the administering the GFAP lowering compound decreases Rosenthal fibers in the subject.

16 . The method of claim 13 , wherein the subject has been diagnosed with or is at risk of gliosis.

17 . The method of claim 13 , wherein the GFAP lowering compound is selected from the group consisting of diaziquone, clomipramine, chrysophanol, amitriptyline, chlorprothixene, EGCDG, mundoserone, amlodipine, ritanserin, irigenol, fluccinonide, hexetidine, estradiol benzoate, ketotifin, clobetasol propionate, colecalciferol, pyrogallin, kanamycin, azinphos methyl, 4-acetamidophenyl salicylate, oxotremorine, ritodrine, NPPB, chloramphenicol, phosphocreatine, betulinic acid, methylnorlichexanthone, coumophos and mixtures thereof.

18 . A method of treating Alexander disease comprising:

administering to a subject at risk of or diagnosed with Alexander disease a therapeutically effective amount of a GFAP lowering compound.

19 . The method of claim 18 , wherein the administering decreases one or more symptoms selected from the group consisting of:

a) the intensity of megalencelphaly associated with Alexander disease;

b) the amount of Rosenthal fibers;

c) the frequency of seizures; and

d) the intensity of seizures.

Assignments (2)
CONFIRMATORY LICENSE Recorded Apr 23, 2013
From: WISCONSIN ALUMNI RESEARCH FOUNDATION
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 030281/0783 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 12, 2013
From: MESSING, ALBEE; CHO, WOOSUNG; THORSON, JON; GOFF, RANDAL
To: WISCONSIN ALUMNI RESEARCH FOUNDATION
Reel/Frame 029974/0721 →