دورية أكاديمية
أعرض في EDS

Clinical Progress in Hepatic Targeting for Novel Prophylactic Therapies in Hereditary Angioedema.

التفاصيل البيبلوغرافية
العنوان: Clinical Progress in Hepatic Targeting for Novel Prophylactic Therapies in Hereditary Angioedema.
المؤلفون: Riedl MA; Division of Allergy and Immunology, University of California, San Diego, La Jolla, Calif. Electronic address: mriedl@health.ucsd.edu., Bordone L; Ionis Pharmaceuticals, Carlsbad, Calif., Revenko A; Ionis Pharmaceuticals, Carlsbad, Calif., Newman KB; Ionis Pharmaceuticals, Carlsbad, Calif., Cohn DM; Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
المصدر: The journal of allergy and clinical immunology. In practice [J Allergy Clin Immunol Pract] 2024 Apr; Vol. 12 (4), pp. 911-918. Date of Electronic Publication: 2023 Dec 22.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Inc Country of Publication: United States NLM ID: 101597220 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2213-2201 (Electronic) NLM ISO Abbreviation: J Allergy Clin Immunol Pract Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York, NY : Elsevier Inc., [2013]-
مواضيع طبية MeSH: Angioedemas, Hereditary*/genetics , Angioedemas, Hereditary*/prevention & control, Humans ; Bradykinin/therapeutic use ; Bradykinin/metabolism ; Complement C1 Inhibitor Protein/therapeutic use ; Liver/metabolism ; Prekallikrein
مستخلص: Hereditary angioedema (HAE) is typically caused by a deficiency of the protease inhibitor C1 inhibitor (C1INH). The absence of C1INH activity on plasma kallikrein and factor XIIa leads to overproduction of the vasoactive peptide bradykinin, with resulting angioedema. As the primary site of C1INH and prekallikrein production, the liver is recognized as an important therapeutic target in HAE, leading to the development of hepatic-focused treatment strategies such as GalNAc-conjugated antisense technology and gene modification. This report reviews currently available data on hepatic-focused interventions for HAE that have advanced into human trials. Donidalorsen is an investigational GalNAc 3 -conjugated antisense oligonucleotide that binds to prekallikrein mRNA in the liver and reduces the expression of prekallikrein. Phase 2 data with subcutaneous donidalorsen demonstrated a significant reduction in HAE attack rate compared with placebo. Phase 3 trials are underway. ADX-324 is a GalNAc 3 -conjugated short-interfering RNA being investigated in HAE. BMN 331 is an investigational AAV5-based gene therapy vector that expresses wild-type human C1INH and is targeted to hepatocytes. A single intravenous dose of BMN 331 is intended to replace the defective SERPING1 gene and enable patients to produce functional C1INH. A first-in-human phase 1/2 study is ongoing with BMN 331. NTLA-2002 is an investigational in vivo clustered regularly interspaced short palindromic repeats/Cas9-based therapy designed to knock out the prekallikrein-coding KLKB1 gene in hepatocytes; a phase 1/2 study is ongoing. Findings from these and other ongoing studies are highly anticipated with the expectation of expanding the array of treatment options in HAE.
(Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
فهرسة مساهمة: Keywords: ASO; Antisense oligonucleotide; CRISPR/Cas systems; Gene therapy; Hereditary angioedema; Liver; siRNA
المشرفين على المادة: S8TIM42R2W (Bradykinin)
0 (Complement C1 Inhibitor Protein)
9055-02-1 (Prekallikrein)
تواريخ الأحداث: Date Created: 20231224 Date Completed: 20240409 Latest Revision: 20240426
رمز التحديث: 20240427
DOI: 10.1016/j.jaip.2023.12.025
PMID: 38142864
قاعدة البيانات: MEDLINE
الوصف
تدمد:2213-2201
DOI:10.1016/j.jaip.2023.12.025