MILK OF TRANSGENIC ANIMALS CONTAINING HUMAN ALPHA1-ANTITRYPSIN AND USE OF HUMAN ALPHA1-ANTITRYPSIN TO TREAT BILE ACID RELATED DISEASES

摘要

The use of human α1-antitrypsin as a foodstuff or as a medicament, utilizing its capacity to bind steroids and steroid-like substances, and transporting them in biological systems is described. Particularly the direct oral administration of the milk of transgenic animals containing abundant amounts (10-60 g/L) of human α1-AT to reinstate a defect intestinal synthesis or to complement the normal physiological biosynthesis of α1-AT is described. Such treatment will reduce the total body load of bile acids by increasing their gastrointestinal elimination. It is expected to be beneficial for bile acid related diseases such as all cholestatic liver diseases, and bile-reflux gastritis. Such treatment is expected to be particularly beneficial in cases of neonatal cholestasis, as newborns circulate large quantities of hydrophobic bile acids which cause liver injury and may contribute to injury of other tissues. It will be protective in cases where bile acids cause tissue injury such as vasculitis, glomerulonephritis, and inflammatory bowel disease. It will be beneficial against diarrhoea in intestinal bacterial overgrowth and bile acid malabsorption. Increased gastrointestinal elimination of the steroid structure may also reduce the total body load of cholesterol and thus be efficient in the treatment of hyperlipidemia.