Anti-fibrotic mode of action and efficacy of TXA127 as disease modifying therapy of recessive dystrophic epidermolysis bullosa (RDEB): a preclinical studyCompleted
|Project lead||Dr Alexander Nyström|
|Organisation||University of Freiburg Medical Center, Freiburg, GERMANY|
|Partner organizations & collaborators||Prof. Leena Bruckner-Tuderman at University of Freiburg, Medical Center, Germany|
|Project budget||EUR 194,250.00|
|Start date / Duration||01. May 2017 / 12 months|
|Funder(s) / Co-Funder(s)||DEBRA Austria|
|Research area||Skin cancer & fibrosis|
Short lay summary
A major complication of recessive dystrophic epidermolysis bullosa (RDEB) is progressive scarring, fibrosis and formation of mitten deformities of hands and feet. These changes are also connected to an increased risk of developing skin cancer. This project aims to evaluate a novel therapy to reduce scarring and fibrosis and to delay formation of mitten deformities of hands and feet. The compound that we are evaluating is Ang-(1-7), which is naturally occurring in our bodies.
RDEB is a skin fragility disorder caused by genetic deficiency of collagen VII. Progressive soft tissue scarring occurring subsequent to skin blistering is greatly debilitating. Limiting fibrosis could significantly increase functionality and improve the quality of life of patients. Preliminary studies have revealed that TXA127, a pharmaceutical formulation of the naturally occurring peptide, angiotensin (1-7) or Ang(1-7), reduces fibrosis in an RDEB mouse model. TXA127 is an attractive drug candidate because it is well-tolerated and is Phase II ready. We propose to carefully evaluate the therapeutic potential of TXA127 in RDEB. We will perform a three-armed preclinical animal study, delineate TXA127 signaling mechanisms using genetic models and establish relevance for treatment of patients using human skin cells. The aim of the study is to generate data that serves as the basis for a clinical trial evaluating the safety and efficacy of TXA127 for treatment of RDEB.