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dc.contributor.authorBustad, Helene J.
dc.contributor.authorKallio, Juha Pekka
dc.contributor.authorVorland, Marta
dc.contributor.authorFiorentino, Valeria
dc.contributor.authorSandberg, Sverre
dc.contributor.authorSchmitt, Caroline
dc.contributor.authorAarsand, Aasne Karine
dc.contributor.authorMartinez, Aurora
dc.description.abstractAcute intermittent porphyria (AIP) is an autosomal dominant inherited disease with low clinical penetrance, caused by mutations in the hydroxymethylbilane synthase (HMBS) gene, which encodes the third enzyme in the haem biosynthesis pathway. In susceptible HMBS mutation carriers, triggering factors such as hormonal changes and commonly used drugs induce an overproduction and accumulation of toxic haem precursors in the liver. Clinically, this presents as acute attacks characterised by severe abdominal pain and a wide array of neurological and psychiatric symptoms, and, in the long-term setting, the development of primary liver cancer, hypertension and kidney failure. Treatment options are few, and therapies preventing the development of symptomatic disease and long-term complications are non-existent. Here, we provide an overview of the disorder and treatments already in use in clinical practice, in addition to other therapies under development or in the pipeline. We also introduce the pathomechanistic effects of HMBS mutations, and present and discuss emerging therapeutic options based on HMBS stabilisation and the regulation of proteostasis. These are novel mechanistic therapeutic approaches with the potential of prophylactic correction of the disease by totally or partially recovering the enzyme functionality. The present scenario appears promising for upcoming patient-tailored interventions in AIP.en_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.titleAcute Intermittent Porphyria: An Overview of Therapy Developments and Future Perspectives Focusing on Stabilisation of HMBS and Proteostasis Regulatorsen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.rights.holderCopyright 2021 by the authors.en_US
dc.source.journalInternational Journal of Molecular Sciencesen_US
dc.relation.projectNorges forskningsråd: 285295en_US
dc.relation.projectNorges forskningsråd: 261826en_US
dc.relation.projectHelse Vest RHF: 912246en_US
dc.identifier.citationInternational Journal of Molecular Sciences. 2021, 22 (2), 675.en_US

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Navngivelse 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Navngivelse 4.0 Internasjonal