{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T07:22:24Z","timestamp":1792221744748,"version":"4.4.0"},"reference-count":209,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T00:00:00Z","timestamp":1610409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005416","name":"Norges Forskningsr\u00e5d","doi-asserted-by":"publisher","award":["BIOTEK2021 285295"],"award-info":[{"award-number":["BIOTEK2021 285295"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005416","name":"Norges Forskningsr\u00e5d","doi-asserted-by":"publisher","award":["FRIMEDBIO 261826\/F20"],"award-info":[{"award-number":["FRIMEDBIO 261826\/F20"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004257","name":"Helse Vest","doi-asserted-by":"publisher","award":["HV912246"],"award-info":[{"award-number":["HV912246"]}],"id":[{"id":"10.13039\/501100004257","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Acute 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.<\/jats:p>","DOI":"10.3390\/ijms22020675","type":"journal-article","created":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T14:28:53Z","timestamp":1610461733000},"page":"675","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Acute Intermittent Porphyria: An Overview of Therapy Developments and Future Perspectives Focusing on Stabilisation of HMBS and Proteostasis Regulators"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4746-1563","authenticated-orcid":false,"given":"Helene J.","family":"Bustad","sequence":"first","affiliation":[{"name":"Department of Biomedicine, University of Bergen, 5020 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3092-4012","authenticated-orcid":false,"given":"Juha P.","family":"Kallio","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, University of Bergen, 5020 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Vorland","sequence":"additional","affiliation":[{"name":"Norwegian Porphyria Centre (NAPOS), Department for Medical Biochemistry and Pharmacology, Haukeland University Hospital, 5021 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9517-9880","authenticated-orcid":false,"given":"Valeria","family":"Fiorentino","sequence":"additional","affiliation":[{"name":"INSERM U1149, Center for Research on Inflammation (CRI), Universit\u00e9 de Paris, 75018 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sverre","family":"Sandberg","sequence":"additional","affiliation":[{"name":"Norwegian Porphyria Centre (NAPOS), Department for Medical Biochemistry and Pharmacology, Haukeland University Hospital, 5021 Bergen, Norway"},{"name":"Norwegian Organization for Quality Improvement of Laboratory Examinations (Noklus), Haraldsplass Deaconess Hospital, 5009 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Schmitt","sequence":"additional","affiliation":[{"name":"INSERM U1149, Center for Research on Inflammation (CRI), Universit\u00e9 de Paris, 75018 Paris, France"},{"name":"Assistance Publique H\u00f4pitaux de Paris (AP-HP), Centre Fran\u00e7ais des Porphyries, H\u00f4pital Louis Mourier, 92700 Colombes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aasne K.","family":"Aarsand","sequence":"additional","affiliation":[{"name":"Norwegian Porphyria Centre (NAPOS), Department for Medical Biochemistry and Pharmacology, Haukeland University Hospital, 5021 Bergen, Norway"},{"name":"Norwegian Organization for Quality Improvement of Laboratory Examinations (Noklus), Haraldsplass Deaconess Hospital, 5009 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1643-6506","authenticated-orcid":false,"given":"Aurora","family":"Martinez","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, University of Bergen, 5020 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,12]]},"reference":[{"key":"ref_1","unstructured":"Rifai, N., Horvath, A.R., and Wittwer, C. 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