| Preventing the aortic complications of Marfan syndrome: a case-example of translational genomic medicine. | |
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MedLine Citation:
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PMID: 21276043 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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What is already known about this subject Marfan syndrome is a genetic condition with a poor prognosis. Management consists of preventing or slowing the complications of the disease, and surgical intervention when complications, notably aortic root dilatation, become life-threatening. Over recent years considerable progress has been made in understanding the genomic and molecular basis of the condition. What this study adds We summarise the disparate research on the syndrome to highlight how recent major new insights are providing a solid foundation for therapeutic intervention. We demonstrate how translational research is incremental, and how genomics is contributing to speeding up progress. We present research on the syndrome as an illustrative case-example of translational research in practice. ABSTRACT: Aims 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. Methods 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. Results Marfan syndrome shows considerable heterogeneity in clinical presentation. Diagnosis 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-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 evaluation of doxycycline, and both animal studies and small trials, provide early evidence that this widely used antimicrobial agent is useful. Identification of the importance of TGF-β led to evaluation of angiotensin II type I receptor (AT(1) R) blockers with highly promising results. Combination prophylactic therapy would appear rational. Conclusion 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. |
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Authors:
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A Li-Wan-Po; B Loeys; P Farndon; D Latham; C Bradley |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-1-29 |
Journal Detail:
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Title: British journal of clinical pharmacology Volume: - ISSN: 1365-2125 ISO Abbreviation: - Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-1-31 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7503323 Medline TA: Br J Clin Pharmacol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society. |
Affiliation:
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National Genetics Education and Development Centre Morris House C/o Birmingham Women's Hospital Edgbaston Birmingham B15 2TG United Kingdom Center for Medical Genetics, Antwerp University Hospital, B-2650, Belgium. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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