>>Hedgehog Pathway Activation Promotes Coronary Growth
Thursday June 22, 9:00 am ET
Preclinical Data Published in Genes & Development
CAMBRIDGE, Mass.--(BUSINESS WIRE)--June 22, 2006--Curis, Inc. (NASDAQ: CRIS - News), a therapeutic drug development company, today announced the publication of data showing that stimulating the Hedgehog signaling pathway in an adult animal model rapidly increased the density of blood vessels in the heart. These findings provide further support for therapeutically targeting the Hedgehog pathway for both acute ischemic events (heart attacks) as well as for chronic myocardial ischemia. Myocardial ischemia, the interruption of blood flow and oxygen to heart muscle, is the leading cause of heart attacks, with more than one million cases reported every year in the United States. In particular, there remains a need for more effective treatments for so-called "no option" patients with chronic myocardial ischemia.
In the current work, led by Dr. David Ornitz at Washington University School of Medicine in St. Louis, the authors sought to identify novel therapeutic targets for treating myocardial ischemia. Their main approach was to use genetically engineered mice in which the Fibroblast Growth Factor and Hedgehog signaling pathways could be experimentally switched on or off. A key finding was that in the fetus the myocardial Fibroblast Growth Factor signaling pathway triggers a wave of Hedgehog activation resulting in the production of major growth factors for blood vessels, including several Vascular Endothelial Growth Factors (VEGFs) and Angiopoietin. Significantly, the Hedgehog pathway could be directly activated to induce blood vessels.
The researchers extended the study to adult animals and showed that direct Hedgehog pathway activation resulted in increased density of coronary vasculature within five days of treatment. To the authors this rapid response, "...suggests that Hedgehog signaling is a potentially important target for therapy aimed at increasing coronary vascularization and perfusion in the context of myocardial ischemia and acute myocardial infarction." Further studies are ongoing on Hedgehog signaling in the heart to evaluate its usefulness in treating heart disease.
Overall, this study independently confirms previously published research demonstrating the critical role of the Hedgehog pathway in coronary blood vessel development in the fetus and the ability to promote neovascularization in the adult.
Wyeth Pharmaceuticals has licensed rights from Curis for Hedgehog agonist compounds, including small molecule compounds, proteins and polypedtides for systemic treatment of diseases and disorders in humans, which includes systemic treatment of cardiovascular disease. In addition, as part of Curis' collaboration with Wyeth, Curis has retained the right to locally administer Hedgehog agonist compounds for the treatment of cardiovascular disease, including peripheral vascular disease and acute myocardial infarction, or heart attack. Wyeth has a right of first negotiation to obtain an exclusive license to the local cardiovascular applications. If Wyeth declines to exercise its option, or if Curis is unable to reach an agreement with Wyeth on terms within the contractually specified period, Curis is free to seek another collaborator for this program.
The article entitled, "Fibroblast growth factor signals regulate a wave of Hedgehog activation that is essential for coronary vascular development" appears in the June issue of Genes & Development. An online publication of the article is available at genesdev.org. The lead author on the paper is Dr. Kory J. Lavine.<<
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