The DMD gene is made up of 79 pieces called exons. The exons link together to form a code that is read in the cells so that the protein dystrophin can be made. If there is a mutation or fault in the gene the exons no longer fit together and are not readable. The consequence is that very little or no dystrophin is made. Exon skipping drugs hide or ‘patch’ the missing piece so that the exons fit together again and can be read. A functional, although shorter, dystrophin protein is made.

Exon skipping has been shown to work in both the mdx mouse and dog models for Duchenne. 

As the exon skipping drug is designed to skip over a particular exon, different versions need to be made depending on which exons needs to be skipped. The most common mutation is around exon 51 and accounts for approximately 13% of cases of Duchenne.

EXONDYS 51 (previously known as eteplirsen) is an approved treatment in the USA and targets the 51 mutation. 

Company Trial Mutation Phase Location
Sarepta Therapeutics Essence 45 and 53 3 US/UK
NS Pharma RACER 53 53 3 US
Wave Life Sciences DYSTANCE 51 51 Discontinued

Stop Codon Read-Through

Ataluren or Translarna™ is a so-called stop codon read-through drug, produced by the pharmaceutical company PTC Therapeutics, that has the potential to overcome nonsense mutations in the DMD gene. This type of mutation causes cells to stop synthesizing the protein dystrophin before the process is complete. This leads to a short, non-functional dystrophin protein.

Ataluren is licensed in the EU for Duchenne and is an investigational product in other countries, including the US. This means that it is a potential treatment option in the EU and UK for ambulant patients aged 2 years and older with a nonsense mutation. 

It is prescribed under a Managed Access Agreement (MAA). This is an agreement between NHS England and NICE which allows patients to receive new treatments while data is gathered before a final funding decision is taken at the end of 5 years. 

For more information, there is a dedicated website to Translarna

NICE, NHS England and NHS Improvement have reviewed the potential impact of COVID-19 on the delivery of Translarna. The new advice is relevant for patients and/or their carers who are already receiving treatment, as well as those who have not yet started. Please contact the medical team who is managing your treatment if you have any questions about this advice.