| Human studies of angiogenic gene therapy. | |
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MedLine Citation:
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PMID: 19815827 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Despite significant advances in medical, interventional, and surgical therapy for coronary and peripheral arterial disease, the burden of these illnesses remains high. To address this unmet need, the science of therapeutic angiogenesis has been evolving for almost two decades. Early preclinical studies and phase I clinical trials achieved promising results with growth factors administered as recombinant proteins or as single-agent gene therapies, and data accumulated through 10 years of clinical trials indicate that gene therapy has an acceptable safety profile. However, more rigorous phase II and phase III clinical trials have failed to unequivocally demonstrate that angiogenic agents are beneficial under the conditions and in the patients studied to date. Investigators have worked to understand the biology of the vascular system and to incorporate their findings into new treatments for patients with ischemic disease. Recent gene- and cell-therapy trials have demonstrated the bioactivity of several new agents and treatment strategies. Collectively, these observations have renewed interest in the mechanisms of angiogenesis and deepened our understanding of the complexity of vascular regeneration. Gene therapy that incorporates multiple growth factors, approaches that combine cell and gene therapy, and the administration of "master switch" agents that activate numerous downstream pathways are among the credible and plausible steps forward. In this review, we examine the clinical development of angiogenic gene therapy, summarize several of the lessons learned during the conduct of these trials, and suggest how this prior experience may guide the conduct of future preclinical investigations and clinical trials. |
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Authors:
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Rajesh Gupta; Jörn Tongers; Douglas W Losordo |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review |
Journal Detail:
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Title: Circulation research Volume: 105 ISSN: 1524-4571 ISO Abbreviation: Circ. Res. Publication Date: 2009 Oct |
Date Detail:
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Created Date: 2009-10-09 Completed Date: 2009-12-08 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 0047103 Medline TA: Circ Res Country: United States |
Other Details:
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Languages: eng Pagination: 724-36 Citation Subset: IM |
Affiliation:
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Feinberg Cardiovascular Research Institute, Northwestern University and Northwestern Memorial Hospital, Chicago, IL 60611, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Clinical Trials, Phase II as Topic Clinical Trials, Phase III as Topic Coronary Artery Disease / genetics, therapy* Gene Therapy / methods* Humans Intercellular Signaling Peptides and Proteins* Ischemia / genetics, therapy* Neovascularization, Physiologic* |
| Grant Support | |
ID/Acronym/Agency:
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HL-53354/HL/NHLBI NIH HHS; HL-57516/HL/NHLBI NIH HHS; HL-63414/HL/NHLBI NIH HHS; HL-77428/HL/NHLBI NIH HHS; HL-80137/HL/NHLBI NIH HHS; HL95874/HL/NHLBI NIH HHS; P01HL-66957/HL/NHLBI NIH HHS; R01 HL053354-11A2/HL/NHLBI NIH HHS; R01 HL057516-07/HL/NHLBI NIH HHS; R01 HL057516-08/HL/NHLBI NIH HHS; R01 HL057516-11/HL/NHLBI NIH HHS; R01 HL057516-12/HL/NHLBI NIH HHS; R01 HL063414-07/HL/NHLBI NIH HHS; R01 HL063414-08/HL/NHLBI NIH HHS; R01 HL077428-01A2/HL/NHLBI NIH HHS; R01 HL077428-02/HL/NHLBI NIH HHS; R01 HL077428-03/HL/NHLBI NIH HHS; R01 HL080137-01A1/HL/NHLBI NIH HHS; R01 HL080137-02/HL/NHLBI NIH HHS; R01 HL080137-03/HL/NHLBI NIH HHS; R01 HL080137-04/HL/NHLBI NIH HHS; R01 HL095874-01/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Intercellular Signaling Peptides and Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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