Gene therapy for acute intermittent porphyria

Gene therapy for acute intermittent porphyria

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Despite the challenges, gene therapy remains a viable treatment alternative for severe genetic disorders. An EU-funded consortium is giving patients suffering from acute intermittent porphyria (AIP) a therapeutic option based on the delivery of a functional gene into the liver.

AIP is a rare genetic disease caused by mutations in the porphobilinogen deaminase (PBGD), a protein necessary for haeme synthesis. This leads to an accumulation of toxic intermediates, resulting in various problems such as acute abdominal pains, psychiatric and neurological disorders, and muscular weakness.

AIP is life-threatening and the long-term consequences include irreversible nerve damage, liver cancer and kidney failure. The only therapy is liver transplantation and, thus, new curative options are clearly needed.

The objective of the EU-funded 'Augmenting PBGD expression in the liver as a novel gene therapy for acute intermittent porphyria' (Aipgene) project is to provide an alternative gene therapy treatment option for AIP. The plan is to use adeno-associated virus (AAV), a replication-incompetent virus, to deliver the PBGD gene directly into hepatocytes.

One of the consortium's industrial partners is producing a clinical quality virus that could be used in a phase I clinical trial. The therapeutic efficacy of the vector has been tested in animal models of AIP, demonstrating a reduction in acute porphyria attacks. Also, administration of high-vector doses into non-human primates has shown no particular side-effects or toxicity.

One of the advantages of the delivery system chosen by Aipgene partners is that the vector remains mainly episomal with a few integrations, thereby minimising integration-related mutagenesis.

More details can be found at the following link: http://cordis.europa.eu/fetch?CALLER=OFFR_TM_EN&ACTION=D&RCN=10987