Current and innovative emerging therapies for porphyrias with hepatic involvement

JOURNAL OF HEPATOLOGY

卷:71

Review

Fontanellas, Antonio^1,2,3  Avila, Matias A.^1,2,3  Anderson, Karl E.^4,5,6  Deybach, Jean-Charles⁷ 

[1] Univ Navarra, Ctr Appl Med Res CIMA, Hepatol Program, Navarra, Spain

[2] Inst Invest Sanitaria Navarra IdiSNA, Pamplona, Spain

[3] Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain

[4] Univ Texas Med Branch, Div Gastroenterol, Dept Prevent Med, Porphyria Lab & Ctr, Galveston, TX 77555 USA

[5] Univ Texas Med Branch, Div Gastroenterol, Dept Community Hlth, Galveston, TX 77555 USA

[6] Univ Texas Med Branch, Div Gastroenterol, Dept Internal Med, Galveston, TX 77555 USA

[7] Univ Paris 07, AP HP, CRMR Porphyries France, Paris 7, France

关键词: Porphyrias;    mRNA therapy;    Heme synthesis;    RNA interference technology;    Liver gene therapy;    Direct-acting antiviral agents and PCT;    Hematopoietic-stem-cell-based gene therapy;    Lentiviral vectors;    Melanogenesis stimulator;    Antisense oligonucleotide therapy;   

DOI  :  10.1016/j.jhep.2019.05.003

来源: Elsevier

【 摘 要 】

Porphyrias are rare inherited disorders caused by specific enzyme dysfunctions in the haem synthesis pathway, which result in abnormal accumulation of specific pathway intermediates. The symptoms depend upon the chemical characteristics of these substances. Porphyrins are photoreactive and cause photocutaneous lesions on sunlight-exposed areas, whereas accumulation of porphyrin precursors is related to acute neurovisceral attacks. Current therapies are suboptimal and mostly address symptoms rather than underlying disease mechanisms. Advances in the understanding of the molecular bases and pathogenesis of porphyrias have paved the way for the development of new therapeutic strategies. In this Clinical Trial Watch we summarise the basic principles of these emerging approaches and what is currently known about their application to porphyrias of hepatic origin or with hepatic involvement. (C) 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

【 授权许可】

Free