Prof Andrew South

Combining multiple drugs to reduce inflammation and scarring in Epidermolysis Bullosa (EB)

Grant Title: Multimodality targeting of chronic inflammation and fibrosis in Epidermolysis Bullosa 

Investigator: Professor Andrew South, Jefferson Medical College, USA

Co-investigator: Dr Alexander Nystrom, University of Frieberg, Germany

Institutions: Jefferson Medical College, USA and University of Frieberg, Germany

Start Date:  06/01/2020 for 2 years

Grant Amount: €126,132.38 (Co-funded by DEBRA Austria) 

Research Type: Pre-clinical

Lay Summary

This project aims to examine whether combinations of 3 different drugs (losartan, trametinib and RTA408) can have synergistic effects in reducing inflammation and fibrosis (scarring) in two mouse models of EB for potential development for use clinically.  

The study will investigate improved outcomes compared to the use of single drugs and reduced toxicity if lower doses of individual drugs are sufficient when used in combination. Losartan and trametinib are already FDA approved and used in clinical practice for other indications, and RTA408 is currently in clinical development for use in other indications.  

About this research and why it is important

This project, original conceived by the late Professor Ulrich Rodeck, is looking at three different drugs, each with a separate mode of action but all targeting the same problem – the inflammation and fibrosis that drives many of the symptoms of EB. Our hope is that together these three drugs will be better than one drug on its own and our research will provide a blueprint for future clinical trials.”  – Prof Andrew South

 “The use of drug combinations are becoming increasingly important for the treatment of complex diseases such as those where inflammation and fibrosis are prevalent. Here we are looking at combinations of three drugs, each with a proven track record in the laboratory, with the aim of finding a “sweet spot” for treating patients with EB.” – Dr Alexander Nystrom

Investigator Biography

Prof Andrew South is a professor at Thomas Jefferson University, Philadelphia, USA. His laboratory focuses primarily on cutaneous SCC (cSCC) which is the most frequent skin cancer with malignant potential and contributes to greater than 1 in 4 skin cancer deaths in Caucasian populations. Patient groups with a high propensity to develop these tumors face a significant risk of mortality. One such group is the genetic skin blistering condition recessive dystrophic epidermolysis bullosa (RDEB). His laboratory has a long standing interest in trying to understand why mutations in the single COL7A1 gene lead to frequent and multiple life-threatening skin cancers.

 

 

 

 

Dr Alexander Nystrom is a group leader in the Department of Dermatology, Medical Centre at the University of Freiburg, Germany. His research group’s translational research is focused on dissecting the roles of the extracellular matrix in skin during homeostasis, normal and pathological wound healing, immune surveillance and in cancer. They use this knowledge to develop new therapy approaches for treatment of bacterial infections, fibrosis and squamous cell carcinoma. A specific interest is on improving the understanding of disease mechanisms in the genetic skin blistering disease, dystrophic epidermolysis bullosa, toward developing safe, efficacious targeted-treatment.