Hyperammonemia, a condition present in patients with urea cycle disorders (UCDs) or liver diseases, can cause neuropsychiatric\ncomplications, which in the worst cases result in brain damage, coma or death. Diverse treatments exist for the treatment of\nhyperammonemia, but they have limited efficacy, adverse effects and elevated cost. Gene therapy is a promising alternative that is\nexplored here. A baculovirus, termed Bac-GS, containing the glutamine synthetase (GS) gene was constructed for the in vitro and\nin vivo treatment of hyperammonemia. Transduction of MA104 epithelial or L6 myoblast/myotubes cells with Bac-GS resulted in a\nhigh expression of the GS gene, an increase in GS concentration, and a reduction of almost half of exogenously added ammonia.\nWhen Bac-GS was tested in an acute hyperammonemia rat model by intramuscularly injecting the rear legs, the concentration of\nammonia in blood decreased 351 ?M, in comparison with controls. A high GS concentration was detected in gastrocnemius muscles\nfrom the rats transduced with Bac-GS. These results show that gene delivery for overexpressing GS in muscle tissue is a promising\nalternative for the treatment of hyperammonemia in patients with acute or chronic liver diseases and hepatic encephalopathy\nor UCD
Loading....