Preclinical trial of Apo AI conjugate with porphobilinogen deaminase for early treatment of acute porphyria crises. Validation of urinary VDBP as a predictive biomarker
Acute intermittent porphyria (AIP) is a metabolic disease caused by a genetic deficiency of porphobilinogen deaminase (PBGD). Clinically, it is characterized by abdomino-psychic-neurological crises associated with serum accumulation of heme precursors of hepatic origin.
The conjugation of PBGD with Apolipoprotein AI does not alter the catalytic capacity of the enzyme and improves its therapeutic efficacy in the 3 compartments involved in the porphyria attack: it increases its half-life in serum, and favors transfer to the liver and nervous system.
The first objective is to optimize the therapeutic efficacy of the conjugate and to design a large-scale production protocol under GMP conditions. The efficacy in the PAI mouse and the toxicity after single administration in mouse and rat and after repeated doses in rat will be analyzed. Previously we proved that the porphyric liver secretes a highly glycosylated Vitamin D Binding Protein (VDBP) which is eliminated in the urine.
The degree of glycosylation increases in patients with chronic PAI and normalizes after PBGD gene therapy in the PAI mouse or after liver transplantation in patients.
The second objective is to collect urine from patients with sporadic and chronic crises to evaluate the efficacy of urinary VDBP as a biomarker able to anticipate the onset of acute porphyria attack.
- Convocation: Health R&D Projects. AES 2015
- Reference: PI15/01951
- Duration: 3 years
- Start date: January 1, 2016
- End date: December 31, 2018
- Funder: Instituto de Salud Carlos III y cofinanciado por el Fondo Europeo de Desarrollo Regional (FEDER) “Una manera de hacer Europa”
- Grant: 272.552,50 €
- Nature of project: National