Friday 1 March 2013
Using exon skipping technology in a model system of Ullrich congenital muscular dystrophy
A group of scientists from Italy has used exon skipping technology to restore the production of a protein called collagen VI in a model system of Ullrich congenital muscular dystrophy. The researchers used cells grown in the laboratory to demonstrate proof of principle that exon skipping might have the potential to be developed as a treatment for some people with this condition.
Collagen VI is a protein produced by our muscle cells which is transported to the outside of the cells where it forms a mesh that surrounds the muscle cells and supports their structure. Mutations in the genes that carry the instructions for the collagen VI protein can stop the protein assembling into the correct shape which can disrupt the mesh of collagen VI which usually forms around the muscle cells. This can lead to Ullrich congenital muscular dystrophy.
Usually, everyone inherits two copies of every gene - one copy from each parent. Some cases of Ullrich congenital muscular dystrophy are caused by a mutation in one of the copies of the collagen VI genes (this is called autosomal dominant inheritance) Scientists believe the collagen VI protein is produced from the mutated gene as normal, but when it is built into the mesh outside the muscle cells it forms the wrong structure. This disrupts the structure of the whole mesh and can lead to progressive wasting of the muscles.
The researchers designed molecular patches that bound to the mutated gene and stopped it being made into a protein. The healthy copy of the gene could still be read and made into a protein as normal. When the cells with the mutated collagen VI gene were grown in the laboratory, there was no mesh of collagen VI. When the molecular patches were added to the cells, the collagen VI produced by the cells could form the ordered mesh seen around healthy cells.
This study provides proof of principle that exon skipping technology may have the potential to be developed to treat some forms of Ullrich congenital muscular dystrophy. It could not be used to treat all forms of the condition. However, the research is in the very early stages, using cells grown in the laboratory. Before the technology could be tested in clinical trials, researchers will need to carry out further tests in animal models to confirm the results and to improve and optimise the technology.
Read about Ullrich congenital muscular dystrophy
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