Mechanistic modelling of enzyme-restoration effects of new recombinant liver-targeted proteins in acute intermittent porphyria.

ABSTRACT:

Background and purpose

Acute intermittent porphyria (AIP) is a rare disease caused by a genetic mutation in the hepatic activity of the porphobilinogen-deaminase. We aimed to develop a mechanistic model of the enzymatic restoration effects of a novel therapy based on the administration of different formulations of recombinant human-PBGD (rhPBGD) linked to the ApoAI lipoprotein. This fusion protein circulates in blood, incorporating into HDL and penetrating hepatocytes.

Experimental approach

Single i.v. dose of different formulations of rhPBGD linked to ApoAI were administered to AIP mice in which a porphyric attack was triggered by i.p. phenobarbital. Data consist on 24 h urine excreted amounts of heme precursors, 5-aminolevulinic acid (ALA), PBG and total porphyrins that we

SUBMITTER: Vera-Yunca D 

PROVIDER: S-EPMC9310908 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature