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Augmenting PBGD expression in the liver as a Novel Gene therapy for Acute Intermittent Porphyria

Objective

Acute intermittent porphyria (AIP) is a rare genetic disease in which mutations in the porphobilinogen deaminase (PBGD) gene produce insufficient activity of a protein necessary for heme synthesis. This leads to an accumulation of toxic intermediates resulting in a wide variety of problems including acute, severe abdominal pains, psychiatric and neurological disorders, and muscular weakness. Acute porphyric attacks can be life-threatening and the long-term consequences include irreversible nerve damage, liver cancer and kidney failure. AIP affects 1/10,000 people in the EU and the therapies currently available do not prevent the symptoms or consequences of acute porphyric attacks. The only curative therapy is liver transplantation and thus, new curative options are clearly needed. In 2009, the European Medicines Agency granted Orphan Drug Designation to AAV5-AAT-PBGD for the treatment of AIP. AAV is a replication-incompetent virus that has been modified to deliver genes or genetic material into human tissues or cells. AAV5-AAT-PBGD acts by delivering the PBGD expression cassette directly into hepatocytes. In heterozygous AIP patient that show 50% of the normal activity the additional PBGD activity will be sufficient to prevent the accumulation of toxic metabolites and thus, to prevent porphyric attacks. the aim of this project is the clinical development of the orphan drug AAV-AAT-PBGD for use to treat AIP. The project will be performed in three different phases. In the first phase, we will develop a GMP-compliant process to produce sufficient AAV5-AAT-PBGD for clinical trials, and we will constitute the largest possible cohorts to improve the follow-up of patients and determine the clinical criteria to select patients for gene therapy. In the second phase, the safety and efficacy of AAV5-AAT-PBGD will be explored in a dose escalation clinical phase I/II trial.

Call for proposal

FP7-HEALTH-2010-single-stage
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Coordinator

FUNDACION PARA LA INVESTIGACION MEDICA APLICADA FIMA
Address
Avenida De Pio Xii 55
31008 Pamplona
Spain
Activity type
Research Organisations
EU contribution
€ 822 842
Administrative Contact
Andrew Solomon (Dr.)

Participants (6)

AMSTERDAM MOLECULAR THERAPEUTICS (AMT) NV
Netherlands
EU contribution
€ 1 092 012
Address
Meibergdreef 61
1105BA Amsterdam
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Tamara Tugal (Dr.)
UNIVERSIDAD DE NAVARRA
Spain
EU contribution
€ 508 800
Address
Campus Universitario Edificio Central
31080 Pamplona
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Iñigo Uriarte-Pueyo (Dr.)
REGION STOCKHOLM
Sweden
EU contribution
€ 70 000
Address
Hantverkargatan 45
104 22 Stockholm
Activity type
Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)
Administrative Contact
Veronica åkers (Ms.)
DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG
Germany
EU contribution
€ 321 100
Address
Im Neuenheimer Feld 280
69120 Heidelberg
Activity type
Research Organisations
Administrative Contact
Bettina Crispin (Ms.)
DIGNA BIOTECH, S.L
Spain
EU contribution
€ 448 000
Address
Avenida Pio Xii 22 Officina 2
31008 Pamplona
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Astrid Pañeda (Dr.)
SERVICIO MADRILENO DE SALUD
Spain
EU contribution
€ 45 400
Address
Plaza Carlos Trias Bertran 7
28020 Madrid
Activity type
Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)
Administrative Contact
Maria Del Mar López Martín (Ms.)