ArticleMolecular therapy : the journal of the American Society of Gene Therapy2010
AAV8-mediated gene therapy prevents induced biochemical attacks of acute intermittent porphyria and improves neuromotor function.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 62 citations in OpenAlex.
- Animal Models of Porphyria with Hepatic Involvement.Seminars in liver disease · 2025Review
- Pathogenesis and clinical management of liver damage in porphyrias: Mechanisms and therapeutic approaches.World journal of hepatology · 2025Review
- Understanding Hepatic Porphyrias: Symptoms, Treatments, and Unmet Needs.Seminars in liver disease · 2024Review
- Article
- Article
- mRNA-based therapy in a rabbit model of variegate porphyria offers new insights into the pathogenesis of acute attacks.Molecular therapy. Nucleic acids · 2021Article
- Acute Intermittent Porphyria: An Overview of Therapy Developments and Future Perspectives Focusing on Stabilisation of HMBS and Proteostasis Regulators.International journal of molecular sciences · 2021Review
- Therapeutic strategies for acute intermittent porphyria.Intractable & rare diseases research · 2020Review
- Porphyric Neuropathy: Pathophysiology, Diagnosis, and Updated Management.Current neurology and neuroscience reports · 2020Review
- Review
- DDIEM: drug database for inborn errors of metabolism.Orphanet journal of rare diseases · 2020Article
- Severe hydroxymethylbilane synthase deficiency causes depression-like behavior and mitochondrial dysfunction in a mouse model of homozygous dominant acute intermittent porphyria.Acta neuropathologica communications · 2020Article
- The future of gene-targeted therapy for hereditary tyrosinemia type 1 as a lead indication among the inborn errors of metabolism.Expert opinion on orphan drugs · 2020Article
- Murine models of the human porphyrias: Contributions toward understanding disease pathogenesis and the development of new therapies.Molecular genetics and metabolism · 2019Review
- Homozygous hydroxymethylbilane synthase knock-in mice provide pathogenic insights into the severe neurological impairments present in human homozygous dominant acute intermittent porphyria.Human molecular genetics · 2019Article
- Porphyrin-Induced Protein Oxidation and Aggregation as a Mechanism of Porphyria-Associated Cell Injury.Cellular and molecular gastroenterology and hepatology · 2019Review
- Acute Hepatic Porphyrias in Colombia: An Analysis of 101 Patients.JIMD reports · 2019Article
- Systemic messenger RNA as an etiological treatment for acute intermittent porphyria.Nature medicine · 2018Article
- Efficient Gene Delivery and Expression in Pancreas and Pancreatic Tumors by Capsid-Optimized AAV8 Vectors.Human gene therapy methods · 2017Article
- Helper-dependent adenovirus achieve more efficient and persistent liver transgene expression in non-human primates under immunosuppression.Gene therapy · 2015Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Acute intermittent porphyria (AIP), an autosomal dominant hepatic porphyria due to half-normal hydroxymethylbilane synthase (HMB-synthase) activity, is manifested by life-threatening acute neurological attacks that are precipitated by factors that induce heme biosynthesis. The acute attacks are currently treated with intravenous hemin, but a more continuous therapy is needed, particularly for patients experiencing frequent attacks. Thus, a recombinant AAV8-based serotype vector expressing murine HMB-synthase driven by liver-specific regulatory elements was generated and its effectiveness to prevent the biochemical induction of an acute attack was evaluated in an AIP mouse model. Intraperitoneal administration of the adeno-associated viral (AAV) vector resulted in a rapid and dose-dependent increase of HMB-synthase activity that was restricted to the liver. Stable expression of hepatic HMB-synthase was achieved and wild-type or greater levels were sustained for 36 weeks. When heme synthesis was periodically induced by a series of phenobarbital injections, the treated mice did not accumulate urinary delta-aminolevulinic acid (ALA) or porphobilinogen (PBG), indicating that the expressed enzyme was functional in vivo and prevented induction of the acute attack. Further, rotarod performance and footprint analyses improved significantly. Thus, liver-directed gene therapy provided successful long-term correction of the hepatic metabolic abnormalities and improved neuromotor function in the murine model of human AIP.
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