Translarna

Introduction

Point mutations are small changes in the DNA that alter the code for an amino acid (protein subunit) into the code for another amino acid or into a stop signal. Stop signals are normally only present at the end of an mRNA and inform the cell that the newly produced protein is complete.

Translarne medicine — Figure 1. Messenger RNA contains the genetic code for a protein. The translation of the mRNA intro protein is performed by the protein factory. This factory needs a “start” signal to initiate protein translation (in the first exon) and a stop signal (at the end of the mRNA, i.e. exon 79 for dystrophin) to indicate that the protein is complete.

translarna — *Figure 2. Stop mutation causes the premature stop of the protein translation (and thus only half a protein is created).*

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.

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 close to other signals needed for mRNA processing, 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 prematurely.

Translarna 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. The real stop signal (at the end of mRNA (or at a busy crossing) are not ignored.

Translarna does not work for 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. Translarna will not change this (even with Translarna the parts that make a model airplane, still cannot make a model car).