Therapeutic area

AAV-Porphyria

Acute Intermittent Porphyria (AIP) represents an inborn error in haem biosynthesis, in which porphobilinogen deaminase (PBGD), also known as hydroxymethylbilane synthase (HMBS), is partially deficient. Prevalence of AIP is estimated at 1 in 20,000 in the general population. The overt disease is characterised by acute attacks of abdominal pain, muscular weakness, and a complex array of neuro-visceral and psychiatric symptoms that can be life-threatening. Current treatment involves glucose and haem administration; however significant side-effects have been noted. More importantly, although immediate treatment for acute attacks is thus provided, the less obvious but progressive neurological damage is left unchallenged. DIGNA-biotech in collaboration with the ducht biotechnology company Amsterdam Molecular Therapeutics (AMT) is developing a gene therapy for AIP to replenish PBGD levels, thereby removing the cause of the disease and preventing recurrences of acute attacks. Using an adeno-associated vector (AAV) to deliver the gene and to provide long-term PBGD expression in the liver, output of toxic metabolic intermediates and neurological damage is permanently halted. Once safety and therapeutic efficacy has been shown and the product has been registered, PBGD gene therapy may be considered for all AIP patients.