A new study led by the University of Portsmouth has shed new light on how Duchenne muscular dystrophy (DMD), a genetic disorder notorious for its devastating impact on muscles, also significantly alters brain function. Published in the journal Molecular Medicine, the research reveals that DMD’s neurological effects are diverse, region-specific, and, in some cases, potentially reversible. These findings could pave the way for treatments that extend beyond muscle degeneration to improve cognitive and behavioural outcomes for those affected.
DMD affects approximately 1 in 5,000 male births worldwide and stems from mutations in the DMD gene, which disrupt the production of dystrophins – proteins critical for both muscle and brain health. While the condition’s hallmark is progressive muscle wasting, the new study highlights its profound neuropsychiatric consequences, including learning difficulties, memory impairments, and heightened risks of ADHD and autism. For decades, medical focus has remained on the muscular symptoms, which ultimately prove fatal. But this research underscores the urgent need to address the brain’s role in the disease.
Professor Darek Gorecki, senior author from the School of Medicine, Pharmacy and Biological Sciences at the University of Portsmouth, emphasises this shift in perspective. “For decades, we’ve focused on the muscles as their damage causes death of the patients,” he says. “But the brain is also deeply affected by DMD. Understanding these changes is crucial to developing treatments that address the full scope of the disease – not just its muscle symptoms.”
The study, conducted by a team of 21 scientists across eight research centres, used RNA sequencing and functional brain analyses to explore how the absence of full-length dystrophins disrupts brain development and metabolism. Their findings show that these abnormalities vary across brain regions and evolve over time. For instance, the cerebrum—encompassing the hippocampus, cerebral cortex, and amygdala – and the cerebellum exhibit distinct patterns of impairment. Intriguingly, some changes appear reversible, offering a glimmer of hope for targeted interventions.
“We now understand that these brain abnormalities develop differently in specific brain regions over time, meaning that targeted early intervention could be key,” Professor Gorecki explains. “This discovery gives us real hope that we can improve at least some cognitive and behavioural symptoms in DMD patients.”
Patients with DMD typically have IQs averaging one standard deviation below the general population, with 30 per cent scoring below 70—a threshold often associated with intellectual disability. The research links this cognitive decline to dystrophin deficiency and identifies additional factors exacerbating brain damage. A leaky blood-brain barrier, for example, allows inflammatory molecules from degenerating muscles to infiltrate the brain, potentially worsening symptoms.
Professor Gorecki highlights the therapeutic implications: “This means that we have a window of opportunity to intervene. By targeting these defects occurring after birth, we potentially could improve cognitive function in DMD patients.” The study suggests several strategies, including restoring dystrophin to the brain to reverse certain cognitive impairments, using anti-inflammatory treatments to mitigate immune overactivation, and exploring dietary approaches like the ketogenic diet to enhance brain metabolism.
“These findings give hope that we’re not just treating symptoms, we might actually be able to change the trajectory of the disease,” Professor Gorecki adds. This optimism is grounded in the study’s detailed mapping of DMD’s neurological impact, which could guide the development of precision therapies tailored to specific brain regions and developmental stages.
