UCLA researchers in the Department of Medicine have uncovered a new use of cilengitide for the treatment of dysregulated wound healing in Classic Ehlers-Danlos syndrome.
BACKGROUND:
Classic Ehlers-Danlos syndrome (cEDS) is a genetic disease that weakens the connective tissues in the body. Mutations in the Col5a1 or Col5a2 genes mean that production of type V collagen, a structural protein found in connective tissues, is disrupted. The disease occurs in about 1 out of every 20,000 people. One of the features of cEDS is dysregulated wound healing that leads to large scars that easily crack or rupture. There are no therapies currently available to assist wound healing in cEDS.
INNOVATION:
UCLA researchers worked with a mouse model of EDS that had the same dysregulated wound healing and scarring as is found in humans with cEDS. In this mouse model, a specific set of integrins - proteins that work in cell-to-cell adhesion - were observed to be the cause of the wound dysregulation. A drug called cilengitide that inhibits specific integrins was tested against these mice. Cilengitide was found to prevent abnormal scar formation. The wound healing and scar size in the EDS mice matched the wound healing and scar size in normal mice.
POTENTIAL APPLICATIONS:
• Treat dysregulated wound healing in Classic Ehlers Danlos syndrome
• Regulating scar size after a heart attack
• Treating individuals with dysregulated scarring/keloids etc
ADVANTAGES:
• First therapy of its kind to regulate scar size
DEVELOPMENT-TO-DATE:
This drug has been tested in mice models and found to completely rescue the phenotype.
RELATED PAPERS:
Yokota T, McCourt J, Ma F, Ren S, Li S, Kim TH, Kurmangaliyev Y, Ahadian S, Nasiri R, Nguyen T, Haw M, Zhou Y, Wu R, Rodriguez A, Cohn W, Wang Y, Julian Whitelegge, Ryazantsev S, Khadamhosseini A, Teitell MA, Eric Chiou, Rowat AC, Crosbie RH, Pellegrini M, Seldin M, Lusis AJ, Deb A. Type V collagen in scar tissue regulates the size of scar after heart injury. Cell. 2020 (In revision).
Lin, L.-Y. et al. Systems Genetics Approach to Biomarker Discovery: GPNMB and Heart Failure in Mice and Humans. G3 8, 3499–3506 (2018).
Yu, J. et al. Topological Arrangement of Cardiac Fibroblasts Regulates Cellular Plasticity. Circ. Res. 123, 73–85 (2018).
Deb, A. Cell-cell interaction in the heart via Wnt/β-catenin pathway after cardiac injury. Cardiovasc. Res. 102, 214–223 (2014).
Deb, A. & Ubil, E. Cardiac fibroblast in development and wound healing. J. Mol. Cell. Cardiol. 70, 47–55 (2014).