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 a1-antitrypsin, carbamazepine was able to decrease levels of the mutant protein. Furthermore, carbamazepine reduced the hepatic load of mutant a1 -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 a1 -antitrypsin exhibit toxic accumulations of the protein, treatment according to the invention may be used to ameliorate symptoms and signs of disease.