Cyrille Vaillend, Yoshitsugu Aoki, Eugenio Mercuri, Jos Hendriksen, Konstantina Tetorou, Aurélie Goyenvalle, Francesco Muntoni. Duchenne Muscular Dystrophy: Recent insights in brain related comorbidities. Nature Communications. 2025, Volume 16, Article 1298.

https://www.nature.com/articles/s41467-025-56644-w

Duchenne muscular dystrophy (DMD) is a severe genetic condition primarily affecting muscle strength of affected boys, but it can also affect the brain, leading to a range of problems including anxiety, autism or intellectual disability. While the process that causes muscle weakness in DMD boys is well understood, less is known about the precise reasons leading to the involvement of the brain. In view of the impact of DMD for brain function, there is a growing need to improve the diagnosis and treatment for these brain-related issues.

This manuscript aims to review the current understanding of the brain-related involvement in DMD, including the molecular mechanisms underlying these symptoms, and the potential for genetic therapies to address both muscle and brain dysfunction in DMD patients.

We summarise how recent research has shown that the DMD gene produces various forms of a protein called dystrophin, which is essential not only for muscle but also for brain function. Depending on where mutations occur in the gene, the different forms of dystrophin are affected, which can lead to a variety of brain-related symptoms in patients and animal models. Studies in mouse models have suggested that genetic therapies aimed at restoring brain dystrophin could help to address at least partially these cognitive and behavioural issues.

While these therapies are still being explored in animal models, these studies pave the way to future genetic therapeutic intervention for  boys with DMD. . At the same time our review also highlights the lack of systematic screening and diagnosis of brain symptoms in boys with DMD, and the possibility that current psychopharmacological approaches may offer some relief.

Looking ahead, the development of brain-targeted genetic therapies could provide a solution to the brain-related symptoms of DMD. However, more research is needed to understand how these therapies could be effectively delivered and whether they can significantly improve cognitive and behavioural outcomes. In the meantime, more systematic use of existing therapies and improved diagnostic tools could help manage these challenges and improve quality of life for DMD patients.