Methods of treating disorders associated with protein polymerization

Patent metadata

Field	Value
Publication number	US-9511074-B2
Application number	US-201414535210-A
Country	US
Kind code	B2
Filing date	Nov 6, 2014
Priority date	Aug 3, 2009
Publication date	Dec 6, 2016
Grant date	Dec 6, 2016

Abstract

The present invention relates to methods of treatment of clinical disorders associated with protein polymerization comprising administering, to a subject, an effective amount of carbamazepine, oxcarbazepine or another carbamazepine-like compound. It is based, at least in part, on the discovery that, in cells having a genetic defect in α1-antitrypsin, carbamazepine was able to decrease levels of the mutant protein. Furthermore, carbamazepine reduced the hepatic load of mutant α1-antitrypsin and the toxic effect of that mutant protein accumulation, hepatic fibrosis, in vivo using a mouse model of the disease. As patients having this defect in α1-antitrypsin exhibit toxic accumulations of the protein, treatment according to the invention may be used to ameliorate symptoms and signs of disease.

First claim

We claim:

1. A method of treating Alzheimer's Disease consisting essentially of administering, to a subject in need of such treatment, a therapeutically effective amount of carbamazepine or a carbamazepine-like compound selected from the group consisting of carbamazepine-10,11-epoxide, iminostilbene, dihydrocarbamazepine, ethyl urea, phenyl urea, diphenylurea, dicyclohexylurea, phenytoin, substituted and unsubstituted iminobenzyl compounds, imipramine, (S)-(-)-10-acetoxy-10,11-dihydro-5Hdibenz[b,f]azepine-5-carboxamide (BI 2-093), and 10,11-dihydro-10-hydroxyimino-5Hdibenz[b,f,]azepine-5-carboxamide (BIA 2-024).

2. The method of claim 1 where the carbamazepine-like compound is carbamazepine.

3. The method of claim 1 where the carbamazepine-like compound is oxcarbazepine.

4. The method of claim 1 where the carbamazepine-like compound is metabolized, in the subject, to form 10, 11-dihydro-10-hydroxy-carbamazepine.

Assignees

• Univ Of Pittsburgh—Of The Commonwealth System Of Higher Education

Inventors

• Perlmutter David Hirsch
• Michalopoulos George Konstantine
• Hidvegi Tunde

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61K31/155

  Amidines ([IMAGE cpc-sch-A61K-1029.gif]), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2) · CPC title

• A61P25/16

  Anti-Parkinson drugs · CPC title

• A61K31/55 Primary

  having seven-membered rings, e.g. azelastine, pentylenetetrazole · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title