Two therapies for Duchenne patients are currently being tested in clinical trials, which are applicable only to patients with specific mutations: PTC124 (treats only stop mutations) and exon skipping (restores the genetic code for certain deletions). Here I will explain why these approaches can not be applied to all patients. (An overview of therapeutic approaches currently being developed for DMD can be found on the TREAT-NMD website)
A you can read in the mutations section, a disruption of the genetic code leads to the use of aberrant protein subunits, whereas a point mutations cause a premature stop signal.
Point mutations are small changes in the DNA that alter a protein subunit code into a stop signal. These stop signals are normally only present at the end of an mRNA (figure 1).
Due to stop mutations, in addition to the normal stop signal at the end of the genetic code, an extra stop signal is present in the middle of the genetic code (figure 2).
Generally, there are additional signs that indicate to the protein factory that the translation into protein is almost complete (e.g. normal stop signals are located at the end of the mRNA and not in the middle). You can compare this with a stop sign in traffic: it makes sense at a very busy crossing, but not in the middle of a highway. There is thus a difference between normal and aberrant stop signals. Nevertheless, the protein factory obeys the aberrant stop signal and protein translation is stopped.
PTC124 is a drug that can make the protein factory ignore the stop signals that do not make much sense (in the middle of a highway), so that protein translation can continue and a complete protein can be generated (figure 3). The real stop signal (at the end of mRNA (or at a busy crossing)) are not ignored.
PTC does not affect mutations that disrupt the genetic code (deletions or duplications of one or more exons, small deletions or duplications within an exon, or small mutations that disrupt exon definition during splicing (splice site mutations)). For these mutations, there is not a single stop signal at an unusual place, but rather aberrant protein subunits are included into the protein. PTC will not change this (even with PTC the parts that make a model airplane, still cannot make a model car).
Applicability of exon 51 skipping
Skipping exon 51 is applicable to the largest group of Duchenne patients (13% of all patients). Figure 4 shows how exon 51 skipping can restore the genetic code. Figure 5 explains why exon 51 skipping does not work for mutations that require the skipping of other exons.