Fibrosis has long been associated with the
activation of transforming
growth factor-b by integrin, but the mechanism underlying the process in vivo
was not known. Now, an international team has shown that the
myofibroblast-expressed integrin αV subunit drives fibrogenesis and has proof of concept for
therapeutic intervention with a small molecule integrin aV antagonist from Antegrin Therapeutics LLC.1
The myofibroblast advantage
According to Sheppard, one of the major
advantages of his team's strategy is that targeting integrin-mediated TGFB1
activation has the potential advantage of decreasing toxicity compared with
targeting all TGFB1.
Antegrin, a spinout of the Center for World Health & Medicine at Saint Louis
University, is developing therapies
for fibrotic diseases with an initial focus on IPF. The company provided the
integrin aV inhibitor CWHM 12 for
the published study. David Griggs and Peter Ruminski, cofounders and scientific
advisers at the company, are coauthors of the paper.
Boettner, B. SciBX 6(46); doi:10.1038/scibx.2013.1308
Published online Dec. 5, 2013
1. Henderson, N.C. et
al. Nat. Med.; published online Nov. 10, 2013; doi:10.1038/nm.3282
Contact: Dean Sheppard, University of California, San Francisco, Calif.
Contact: Neil C. Henderson, The University of Edinburgh, Edinburgh, U.K.
2. Wynn, T.A. &
Ramalingam, T.R. Nat. Med. 18, 1028-1040 (2012)
3. Foo, S.S. et al.
Cell 124, 161-173 (2006)
AND INSTITUTIONS MENTIONED
Antegrin Therapeutics LLC, St. Louis, Mo.
Biogen Idec Inc. (NASDAQ:BIIB), Weston, Mass.
Saint Louis University, St. Louis, Mo.
Harvard Medical School, Boston, Mass.
Icahn School of Medicine at Mount Sinai, New York, N.Y.
Karolinska Institute, Stockholm, Sweden
KineMed Inc., Emeryville, Calif.
Max Planck Institute for Molecular Biomedicine, Muenster, Germany
National Institute of Allergy and Infectious Diseases, Bethesda, Md.
National Institutes of Health, Bethesda, Md.
University, St. Louis,
Saint Louis University School of Medicine, St. Louis, Mo.
University of California, San Francisco, Calif.
The University of Edinburgh, Edinburgh, U.K.
University of Muenster, Muenster, Germany
The University of Texas MD Anderson Cancer Center, Houston, Texas
Uppsala University, Uppsala, Sweden