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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.
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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)

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AMSTERDAM MOLECULAR THERAPEUTICS (AMT) NV

Netherlands

EU Contribution

€ 1 092 012

UNIVERSIDAD DE NAVARRA

Spain

EU Contribution

€ 508 800

STOCKHOLMS LANS LANDSTING

Sweden

EU Contribution

€ 70 000

DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG

Germany

EU Contribution

€ 321 100

DIGNA BIOTECH, S.L

Spain

EU Contribution

€ 448 000

SERVICIO MADRILENO DE SALUD

Spain

EU Contribution

€ 45 400

Project information

Grant agreement ID: 261506

Status

Closed project

  • Start date

    1 January 2011

  • End date

    31 October 2014

Funded under:

FP7-HEALTH

  • Overall budget:

    € 4 347 949,14

  • EU contribution

    € 3 308 154

Coordinated by:

FUNDACION PARA LA INVESTIGACION MEDICA APLICADA FIMA

Spain