Publication
Title
Preventing the aortic complications of Marfan syndrome : a case-example of translational genomic medicine
Author
Abstract
The translational path from pharmacological insight to effective therapy can be a long one. We aim to describe the management of Marfan syndrome as a case-example of how pharmacological and genomic insights can contribute to improved therapy. We undertook a literature search for studies of Marfan syndrome, to identify milestones in description, understanding and therapy of the syndrome. From the studies retrieved we then weaved an evidence-based description of progress. Marfan syndrome shows considerable heterogeneity in clinical presentation. It relies on defined clinical criteria with confirmation based on FBN1 mutation testing. Surgical advances have prolonged life in Marfan syndrome. First-line prophylaxis of complications with beta-adrenoceptor blockers became established on the basis that reduction of aortic pressure and heart rate would help. Over-activity of proteinases, first suggested in 1980, has since been confirmed by evidence of over-expression of matrix metalloproteinases (MMP), notably MMP-2 and MMP-9. The search for MMP inhibitors led to the evaluation of doxycycline, and both animal studies and small trials, provided early evidence that this widely used antimicrobial agent was useful. Identification of the importance of TGF-beta led to evaluation of angiotensin II type I receptor (AT(1)R) blockers with highly promising results. Combination prophylactic therapy would appear rational. Pharmacological and genomic research has provided good evidence that therapy with losartan and doxycycline would prevent the aortic complications of Marfan syndrome. If on-going well designed trials confirm their efficacy, the outlook for Marfan syndrome patients would be improved considerably.
Language
English
Source (journal)
British journal of clinical pharmacology. - London
Publication
London : 2011
ISSN
0306-5251
Volume/pages
72:1(2011), p. 6-17
ISI
000292505500002
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 22.01.2014
Last edited 08.12.2017
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