Recessive dystrophic EB: Mechanisms of fibrosis and its prevention with Losartan in vivo (Bruckner-Tuderman 4 + Ext)Completed
|Project lead||Prof Leena Bruckner-Tuderman|
|Organisation||University of Freiburg Medical Center, Freiburg, GERMANY|
|Project budget||EUR 278,060.00 + EUR 106,765.00 (Extension)|
|Start date / Duration||01. Apr 2012 / 48 months|
|Funder(s) / Co-Funder(s)||DEBRA Austria, MSAP/EBEP Recommended|
|Research area||Symptom prevention & relief|
Short lay summary
This project elucidates possibilities to attenuate scarring and fibrosis in recessive dystrophic EB (RDEB). The goal is to test and identify small molecules as pharmacologic “anti-fibrosis” agents, which prevent progressive scarring and improve the texture of the skin. The hope is that softer and less scarred skin would not be prone to develop squamous cell carcinoma.
Our investigations are experimental and pre-clinical studies using mouse models (the so called collagen VII hypomorphic mouse, or RDEB mouse) and skin cells. The first goal is to understand how a “pro-fibrotic” molecule, the transforming growth factor-ß (TGF-ß), acts in RDEB skin. This factor drives fibrotic changes in many diseases, but it is known that the effects are tissue- and disease-specific. Therefore, first, the mode of action of TGF-ß in RDEB will have to be carefully mapped. Thereafter, TGF-ß inhibitors can be tested and their mechanisms of action elucidated. Particular attention will be paid to losartan, an approved drug for the treatment of high blood pressure. Losartan has also anti-fibrotic effects and has been successfully used to prevent fibrotic changes in other hereditary diseases, such as Marfan syndrome of muscular dystrophies. These observations encourage us to hypothesize that losartan may have beneficial effects in RDEB, too.