RE-COMBINING VIRAL AND NON-VIRAL VECTORS CONTAINING THE HUMAN GENE OF THE UROKINASE PLASMINOGEN ACTIVATOR AND ITS BENEFIT IN THE TREATMENT OF DIVERSE TYPES OF HEPATIC, RENAL, PULMONARY, PANCREATIC AND CARDIAC FIBROSIS AND HYPERTROPHIC SCARS.

摘要

It is proposed the use of genetic therapy for cirrhotic livers by means of the specific transmission of the gene of the human urokinase plasminogen activator or (huPA), which activates mechanisms to induce the matrix extracellular excess degradation and stimulates the hepatocytes proliferation, accomplishing with this a fast reestablishment of liver functionality. In the present it was utilized the human gene uPA modified and inserted in the adenoviral vector (pAd-huPA), which is not secreted and does not produce hypo-coagulation or internal spontaneous bleedings; likewise data from the study in bio-distribution with an adenoviral vector with the reporter gene b-gal, has shown the specificity of the liver as target organ of the vector. It was detected the huPA protein by ELISA in liver homogenates (4500 pg/ml) in animals injected with pAd-huPA) and it was also intracellularly detected by immune-histochemical process in liver cuts (80% of positive cells). The huPA caused a dramatic red uction of fibrosis (85% at the 10th day of administrating the vector, compared with control cirrhotic rats and a hepatocytes proliferation of 55%. The hepatic functional tests (ALT, AST, alkaline phosphatase and bilirubin) diminished almost up to normal levels and the hepatocytes proliferation was verified. Due to the two cascades of beneficial events, the gene therapy with the huPA modified can be developed as a definitive potential treatment in patients with hepatic cirrhosis.