DALLAS, Texas—As researchers search for new treatments and a possible cure for Duchenne muscular dystrophy (DMD), one area seems to be neglected: cognitive and behavioral problems in boys and young men with the disease.
Pediatric neurologist Mathula Thangarajh, MD, PhD, of Virginia Commonwealth University in Richmond, chaired a session on that topic during the Muscular Dystrophy Association’s 2023 Clinical & Scientific Conference, which took place here March 19-22, 2023.
Her panel—“Making Visible the Invisible: Cognitive and Behavioral Health in Duchenne”—drove home the point that brain health among DMD patients hasn’t received nearly enough attention when compared to the attention devoted to cardiac, muscular and pulmonary health.
“Parents of young boys will tell you that it is extremely difficult to get resources for mental health,” Dr. Thangarajh told Rare Disease Advisor after her session. “More fundamentally, parents have stated that speech delay, for example, really affects infant‑parent bonding. Communication is fundamental to humans. The fact that these boys can have speech delay and find it difficult to express themselves also means they cannot advocate for themselves.”
In fact, recent studies conducted by Dr. Thangarajh—formerly of Children’s National Medical Center in Washington, DC—show that speech delays affect 33% of patients with DMD 4-8 years of age. Other common problems: developmental delay (24%); significant behavioral issues (16.5%); language impairment and learning disabilities (14%), and autism (3%).
“Speech delay is one of the most common findings in young boys with Duchenne muscular dystrophy,” Dr. Thangarajh said. “Speech is also a motor function. What do young infants and children do? They learn to babble, make sounds, and acquire language. If you look at it as a motoric function, it makes sense that it should be abnormal. Dystrophin in the brain, interestingly, is the second‑highest level of expression in the body, next to skeletal muscles.”
She added that Guillaume-Benjamin-Amand Duchenne de Boulogne—the French neurologist after whom the disease is named—studied 12 boys with progressive muscle weakness and noticed these problems more than 150 years ago.
“Duchenne himself described what he called a dull affect and speech delay in these boys,” she explained. “We have become a little bit more fragmented in the way we deliver care and don’t look at all of the needs of these children holistically. We have lacked greater appreciation of the deficits these children experience. There’s also a lack of informed professionals because when they come to your clinic, you want to prioritize primarily skeletal and cardiac health.”
In fact, close to 85% of boys and young men with Duchenne have never seen a mental health professional, Dr. Thangarajh said, and this is a serious problem.
“I don’t think their physical deficits are any greater than their cognitive needs, especially in younger boys. Preschool and preparing for school is a burden for some parents,” she said. “Even in infants less than 12 months of age, we know that in terms of brain development, they are not meeting certain milestones compared to typically developing infants. For example, they have language deficits. And they have challenges when it comes to attention regulation and executive function, even in infancy.”
Asked about the potential for gene therapy to reverse some of these problems in Duchenne, Dr. Thangarajh said she’s seen no evidence that the therapies now in clinical trials have a way of penetrating the blood-brain barrier.
“We could say it is going to be very beneficial for the skeletal muscle if found effective,” she concluded, “but I don’t think we’re going to see a remarkable change in cognitive health.”