New Study Shows Duchenne's Effect on the Brain Might Be Reversed

Recent research has shown that uncovered that Duchenne muscular dystrophy (DMD), primarily recognized for its severe muscle degeneration, also significantly impacts the brain.

The research, published as a study in Molecular Medicine in March 2025, noted the condition leads to a range of cognitive and behavioral challenges, many of which could potentially be reversed.

Dariusz C. Gorecki, Ph.D., professor of molecular medicine at the University of Portsmouth in England and the senior author, noted DMD affects both the muscle (progressive degeneration and wasting) and brain (cognitive and behavioral abnormalities). Although muscle damage invariably leads to premature mortality, brain symptoms are variable, with 30% of those with DMD experiencing a severe impairment.

Dariusz C. Gorecki, Ph.D.

“Understandably, therapeutic efforts were aimed at muscle symptoms, for which we still have no effective treatment,” he told MHE by email. “However, if they occur, the neuropsychiatric abnormalities exacerbate the disease and complicate care dramatically. Imagine a severe physical disability and, on top of it, cognitive and behavioral problems involving attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD).”

He added that the researchers do not understand why the absence of dystrophin in the brain causes so many different abnormalities.

“One acknowledged component of the cognitive deficit variability is the natural IQ spread: DMD removes about 15 IQ points across all patients, so somebody starting with an IQ of 100 to 120 would not show any deficit; only those at the lower spectrum of the norm would,” Gorecki said.

There are three full-length dystrophins, the deletion of which causes DMD. Only one is found in muscle, but it is the brain that expresses the greatest variety, with two types found in specific brain regions and cells — the hippocampus and cerebral cortex in the cerebrum and Purkinje neurons in the cerebellum, Gorecki explained. If their levels or distribution fluctuate across populations, this could cause the variability.

“Moreover, while muscle disease is progressive, brain abnormalities are not; they appear to happen in development,” Gorecki continued. “But we had little idea when and where in development. We tried to answer these questions in a mouse model of DMD. It is not possible to study human brains, and cell models are too simplistic. We hoped that by comparing two brain regions, the cerebrum and cerebellum, at two timepoints — early after birth and in early adulthood — we would identify a common abnormality caused by the absence of dystrophin irrespective of its localization in the brain and the stage of development.”

There may be another potential reason for the variability, with the researchers pointing out that the organic defects caused by the loss of dystrophin in specific brain regions can be exaggerated by inflammatory mediators released from chronically inflamed dystrophic muscle. Early after birth there is yet no muscle inflammation, while the adult brain would have been significantly exposed.

“For the first time, we demonstrated that the dystrophic alterations are unique to the cerebrum and cerebellum and vary substantially between young and adult brains,” Gorecki said. “The common anomaly appears to affect the mRNA processing pathways. This could result in great variability of symptoms, as different cells in specific brain regions express different mRNAs, and their wrong processing would cause variable consequences.”

During the testing, abnormalities in the cerebrum were significantly more pronounced in younger mice, which means that they occur sometimes during development in utero. But the cerebellum had few changes in youngsters, which indicates that DMD affects the functional maturation of the cerebellum, a process that occurs postnatally.

“These late dystrophic alterations may therefore be amenable to therapeutic intervention, offering potential avenues for mitigating DMD-related neuropsychiatric defects,” Gorecki said. “Of course, further studies are needed, and I do not want to speculate right now what could be done therapeutically, as it would be irresponsible at this stage. There is nothing worse than false hopes. However, we know now that some DMD deficits may be targetable and that we should start as early as possible.”

In fact, Gorecki sees two windows of opportunity from the study.

“The growing area of in utero interventions may be applicable to DMD from carriers,” he said. “However, due to the high frequency of new mutations, DMD prenatal diagnosis will not catch 30% of patients. Yet, DMD can be diagnosed in newborns by a simple and cheap blood test.  At least some of the late cerebellar abnormalities might be targetable, hopefully reducing the symptoms.”