High-content screening for new therapies for Epidermolysis Bullosa Simplex associated with Muscular Dystrophy (EBS-MD)Completed
|Project lead||Prof. Arnoud Sonnenberg|
|Organisation||The Netherlands Cancer Institute (NKI)|
|Project budget||EUR 125,875.00|
|Start date / Duration||01. Apr 2017 / 24 months|
|Funder(s) / Co-Funder(s)||DEBRA Austria, MSAP/EBEP Reviewed|
|Research area||Molecular therapy, Cellular therapy|
Short lay summary
Epidermolysis Bullosa (EB) is a group of genetic diseases characterized by recurrent blistering from minor mechanical friction or trauma. EBS-MD is a clinical subtype caused by mutations in the gene encoding the cytoskeletal linker protein plectin (PLEC1). Currently, there is no effective therapy or cure for EBS-MD.
The aim of this project is to identify small-molecules that are useful for the treatment of EBS-MD. We will take advantage of the fact that many of the PLEC1 mutations occur in a single exon that is subject to alternative mRNA splicing. We will perform high-content/ high-throughput screenings for small molecules that promote skipping of the mutated exon in the RNA to generate a smaller variant of plectin, which as we have recently shown can functionally fully compensate for the absence of full-length plectin in genetically modified mice.
The high-content/high-throughput screening of small molecule libraries proposed in this project will hopefully identify pharmacological compounds that can be tested for its clinical utility in EBS-MD patients.