Developing advanced molecular patch therapy for collagen VI-related congenital muscular dystrophy

Muscle cells are protected and stabilised by collagen VI proteins. Genetic changes in collagen VI genes (particularly COL6A1, COL6A2 and COL6A3) can cause congenital muscular dystrophies, such as Bethlem myopathy and Ullrich congenital muscular dystrophy (UCMD).

Molecular patches, also known as antisense oligonucleotides (ASOs), have previously been identified as a potential therapeutic approach for collagen VI-related congenital muscular dystrophy (COL6-CMD) by Dr Zhou and her collaborators. However, the in vivo (in a living organism) delivery of these molecular patches proved challenging. The researchers were trying to introduce the molecular patches to the cells in the skeletal muscle where collagen VI is produced. These cells are called muscle interstitial fibroblast cells (MIFs). When collagen VI is changed, the faulty protein will mainly be secreted from these MIFs, so it’s important that the molecular patches can target them.

The project aims to develop new molecular patch therapy for COL6-CMD through the following steps:

1. Find a group of peptides (these are small protein building blocks) that preferentially bind to MIFs over other cells/tissues.
2. Test if these peptides (when joined onto a molecular patch) increase the delivery of molecular patches into MIFs.
3. Test if these joined up peptide-molecular patches lead to the correction of gene errors in mouse models, as well as cells and tissues from affected children.

There is currently a bottleneck in the development of successful molecular patch therapies for COL6-CMD. This research would facilitate molecular patch-based clinical trials in the future, with the aim of making therapies and treatments more effective, and reducing the side-effects of molecular patch therapies, thus providing improved treatment options to those with COL6-CMD.