Therapeutic developments for Duchenne muscular dystrophy
Summary by Menahel Sukkena Sajjad
Duchenne muscular dystrophy (DMD) is an inherited disease of the muscles that gradually worsens with time. It is caused by a change in a gene that leads to the production of a faulty version of the protein dystrophin. The main features seen in individuals with DMD are loss of muscle tissue, weakness in the limbs leading to wheelchair dependency by the age of 12, needing support to breathe at the age of around 20, and eventually premature death in the 30s or 40s. Although no cure exists for this disease, many attempts have been made to slow down and manage the disease progression. Increasing the average time that these individuals are expected to live, and their quality of life is important. The paper summarised here reviews the most important and promising treatment approaches that have been researched and shown to be effective in slowing down the disease. Some treatments have already been approved for use; however, some are in the clinical trial phase.
The treatments discussed are divided into primary (that target the change in the gene or restore levels of dystrophin) and secondary (that target the different pathways affected by the loss of protein). Some therapies can act on both the primary fault and the secondary consequences. Drugs named Ataluren and Eteplirsen are treatments being used to address the loss of protein at the moment. Unfortunately, these have their limitations for example not being appropriate for all people with DMD.
In terms of primary treatments, one possible therapy is to replace the faulty gene by injecting the necessary information through a carrier such as a virus. The cells utilise this to produce functional dystrophin, which primarily plays a part in muscle movement both skeletal and cardiac. However, there still needs to be quite a few advances to perfect this method before it can be used. Other treatment methods are based on editing the genes, at the level of our DNA. These changes lead to a slightly functional DMD. Another potential treatment could be Stem Cell therapy, where muscle stem cells that can become functioning muscle cells can be taken from unaffected donors and transplanted into the patient. These would then divide into healthy muscle cells replacing the damaged ones.
The secondary treatments include using anti-inflammatory substances such as corticosteroids. However, there is a lack of understanding of the mechanisms behind how this works highlighting the importance of further research. Other methods include using antioxidants to decrease highly reactive chemical molecules which exacerbate muscle damage. Drugs that dilate (widen) the blood vessels are used to target the decreased amount of oxygen to the affected muscles.
Supportive care for DMD is offered by a wide variety of health professionals and this is vital, as the muscle tissue already lost in people with the condition cannot be restored by these new treatments. The aim is to slow down any more muscle tissue loss and ideally stopping it altogether, and early intervention is seen as having a beneficial effect on this. Further research is important to find effective treatments for this condition as it has devastating effects on individuals and their families. The paper concludes that combinations of treatments are the best way to address both the primary fault and its secondary consequences.
Verhaart, I.E.C., Aartsma-Rus, A. Therapeutic developments for Duchenne muscular dystrophy. Nat Rev Neurol 15, 373–386 (2019). https://doi.org/10.1038/s41582-019-0203-3
Lay summary by Menahel Sukkena Sajjad
Reviewed by Dr Liam Knox