PRODUCTION OF RHPBGD AND NEW THERAPEUTIC METHODS FOR TREATING PATIENTS WITH ACUTE INTERMITTENT PORPHYRIA (AIP) AND OTHER PORPHYRIC DISEASES

摘要

A method for production of rhPBGD in high scale and use of rhPBGD in a methodfor treatment or prophylaxis of disease caused by deficiency, in a subject, ofan enzyme belonging to the heme biosynthetic pathway. The method comprisingadministering, to the subject, an effective amount of one or more catalystwhich is said enzyme or an enzymatically equivalent part or analogue thereofprefreable in combination with a gene therapy of a mutation related to thecatalyst. The disease is selected from the group consisting of acuteintermittent porphyria (AIP), ALA deficiency porphyria (ADP), Porphyriacutanea tarda (PCT), Hereditary coproporphyria (HCP), Harderoporphyria (HDP),Variegata porphyria (VP), Congenital erythropoietic porphyria (CEP),Erythropoietic protoporphyria (EPP), and Hepatoerythropoietic porphyria (HEP).The catalyst is one or more enzymes selected from the group consisting ofdelta-aminolevulininic acid synthetase, delta-aminovulinic acid dehydratase(ALAD), porphobilinogen deaminase (PBGD), uroporphyrinogen III cosythetase,uroporphyrinogen decarboxylase, coproporphyrinogen oxidase, protoporphyrinogenoxidase, and ferrochelatase, or an enzymatically equivalent part or analoguetherof. In addition the invention relates to the use of rhPBGD. The inventionalso relates to an expression plasmid pExp1-M2-BB (seq. ID No.1) and to use ofa DNA fragment, the EcoR I - Hind III linear fragment (seq. ID No. 2), usedfor transformation in the hemC disruption strategy for production of rhPBGDexpressed in E. coli..