发明名称 |
Methods of treating disorders associated with protein polymerization |
摘要 |
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. |
申请公布号 |
US9511074(B2) |
申请公布日期 |
2016.12.06 |
申请号 |
US201414535210 |
申请日期 |
2014.11.06 |
申请人 |
UNIVERSITY OF PITTSBURGH—OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION |
发明人 |
Perlmutter David Hirsch;Michalopoulos George Konstantine;Hidvegi Tunde |
分类号 |
A61K31/55;A61K31/155 |
主分类号 |
A61K31/55 |
代理机构 |
Baker Botts L.L.P. |
代理人 |
Baker Botts L.L.P. |
主权项 |
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). |
地址 |
Pittsburgh PA US |