دورية أكاديمية
Targeting factor D of the alternative complement pathway reduces geographic atrophy progression secondary to age-related macular degeneration.
| العنوان: | Targeting factor D of the alternative complement pathway reduces geographic atrophy progression secondary to age-related macular degeneration. |
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| المؤلفون: | Yaspan BL; Genentech Inc., South San Francisco, CA 94080, USA., Williams DF; VitreoRetinal Surgery, PA, Minneapolis, MN 55404, USA., Holz FG; Department of Ophthalmology, University of Bonn, Bonn, Germany., Regillo CD; Wills Eye Hospital, Philadelphia, PA 19107, USA., Li Z; Genentech Inc., South San Francisco, CA 94080, USA., Dressen A; Genentech Inc., South San Francisco, CA 94080, USA., van Lookeren Campagne M; Genentech Inc., South San Francisco, CA 94080, USA., Le KN; Genentech Inc., South San Francisco, CA 94080, USA., Graham RR; Genentech Inc., South San Francisco, CA 94080, USA., Beres T; Genentech Inc., South San Francisco, CA 94080, USA., Bhangale TR; Genentech Inc., South San Francisco, CA 94080, USA., Honigberg LA; Genentech Inc., South San Francisco, CA 94080, USA., Smith A; Genentech Inc., South San Francisco, CA 94080, USA., Henry EC; Genentech Inc., South San Francisco, CA 94080, USA., Ho C; Genentech Inc., South San Francisco, CA 94080, USA., Strauss EC; Genentech Inc., South San Francisco, CA 94080, USA. strauss.erich@gene.com. |
| مؤلفون مشاركون: | MAHALO Study Investigators |
| المصدر: | Science translational medicine [Sci Transl Med] 2017 Jun 21; Vol. 9 (395). |
| نوع المنشور: | Clinical Trial, Phase II; Journal Article; Multicenter Study; Randomized Controlled Trial |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101505086 Publication Model: Print Cited Medium: Internet ISSN: 1946-6242 (Electronic) Linking ISSN: 19466234 NLM ISO Abbreviation: Sci Transl Med Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : American Association for the Advancement of Science |
| مواضيع طبية MeSH: | Geographic Atrophy/*drug therapy , Geographic Atrophy/*metabolism , Immunoglobulin Fab Fragments/*therapeutic use , Macular Degeneration/*drug therapy , Macular Degeneration/*metabolism, Aged ; Complement Factor D/antagonists & inhibitors ; Complement Factor D/metabolism ; Complement Pathway, Alternative ; Disease Progression ; Female ; Geographic Atrophy/pathology ; Humans ; Macular Degeneration/pathology ; Male ; Middle Aged |
| مستخلص: | Geographic atrophy is an advanced form of age-related macular degeneration (AMD) and a leading cause of vision loss for which there are no approved treatments. Genetic studies in AMD patients have implicated dysregulation of the alternative complement pathway in the pathogenesis of geographic atrophy. Lampalizumab is a potential therapeutic that targets complement factor D, a pivotal activator of the alternative complement pathway. The MAHALO phase 2 clinical trial was a multicenter, randomized, controlled study that evaluated lampalizumab administered by intravitreal injection monthly ( n = 42) and every other month ( n = 41) versus sham control ( n = 40) in patients with geographic atrophy secondary to AMD. The primary endpoint was the mean change in lesion area from baseline to month 18 as measured by fundus autofluorescence. Specific AMD-associated genetic polymorphisms were also analyzed. The MAHALO study met its primary efficacy endpoint with an acceptable safety profile; monthly lampalizumab treatment demonstrated a 20% reduction in lesion area progression versus sham control [80% confidence interval (CI), 4 to 37%]. A more substantial monthly treatment benefit of 44% reduction in geographic atrophy area progression versus sham control (95% CI, 15 to 73%) was observed in a subgroup of complement factor I ( CFI ) risk-allele carriers (57% of the patients analyzed were CFI risk-allele carriers). The MAHALO study shows a potential treatment effect in patients with geographic atrophy and supports therapeutic targeting of the alternative complement pathway for treating AMD pathogenesis. (Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.) |
| المشرفين على المادة: | 0 (Immunoglobulin Fab Fragments) EC 3.4.21.46 (CFD protein, human) EC 3.4.21.46 (Complement Factor D) UWU93Y99R3 (lampalizumab) |
| تواريخ الأحداث: | Date Created: 20170623 Date Completed: 20180403 Latest Revision: 20210503 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1126/scitranslmed.aaf1443 |
| PMID: | 28637922 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1946-6242 |
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| DOI: | 10.1126/scitranslmed.aaf1443 |