1. Strategies based on restoring functional dysferlin protein


Proteins normally fold into predefined structures and when this folding gets messed up the protein cannot function. The way the protein folds is carefully controlled so that it does not form the wrong shape and lose its specific function. There are specific proteins in cells whose job it is to make sure that other proteins fold properly — like molecular teachers instructing the young proteins how to behave.

Gene Therapy

Gene therapy involves a variety of methods to put a functional copy of the dysferlin gene back into muscle cells. No change is made to the mutant gene, but now an additional viable copy of the gene is present. Imagine you are a supervisor and have an employee who is not doing his job. The job needs to get done, but you are not able to fire the ineffective employee because he is the boss's son. So you bring in a new person who can do the job.

Exon Skipping

Think of a mutated dysferlin gene as an electrical wire that has a fault somewhere in the middle. The idea behind exon skipping is to remove the fault by cutting the wire on either side of the fault and then rejoining the two ends of the wire so that the fault is removed. The resulting wire is shorter than the original one, but can potentially still do the same job. A mutated dysferlin gene can also be thought of as a scratched CD.

Stop Codon Readthrough (PTC124/Ataluren)

This strategy applies to dysferlin genes containing a stop codon mutation. Imagine that you are traveling on the road that makes dysferlin protein. In order to obtain a full length dysferlin protein, you need to get to the end of the road. However, somewhere along the road there is a washed-out bridge that stops you from going further. A stop codon mutation is like a washed-out bridge that prevents the cell from manufacturing a full-length dysferlin protein.