Researchers from the University of Florida and Leiden University Medical Center (LUMC) have discovered hundreds of blood proteins in DMD patients that show the disease’s development. Measuring these indicators could assist identify appropriate candidates for clinical trials and promote more individualized treatment decisions because it is less invasive than physical testing or biopsies.
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Duchenne muscular dystrophy
The symptoms of Duchenne muscular dystrophy, a severe and uncommon hereditary disorder that primarily affects young boys, often manifest between the ages of two and five. Over time, their muscles gradually weaken, starting in the legs and later affecting the arms, shoulders, heart and other parts of the body. Most boys with Duchenne lose the ability to walk between the ages of 10 and 12 and become dependent on a wheelchair. As the illness worsens, individuals may also become incapable of breathing on their own, lifting their arms, or feeding themselves, frequently necessitating assisted ventilation in their teens or early adult years.
The challenge of measuring decline in Duchenne muscular dystrophy
Predicting the rate of that decline has proven challenging thus far. Physical tests, such walking a specific distance, reaching aloft, or feeding oneself, are frequently used by doctors. However, these exams aren’t always accurate or unbiased.
“These tests can be exhausting and aren’t always feasible, especially when someone is having a bad day physically. We also know that young children sometimes perform better when they’re promised a reward, which means the results can’t always be trusted. And because every patient progresses differently, you can’t easily compare one person’s decline to another’s. That’s why we need objective tools, like blood-based biomarkers, that give us a clearer picture of someone’s current condition and how it’s changing,” says Nadine Ikelaar, PhD student at the Neurology department.
The benefits of a blood test
A blood test is far less burdensome than a walking test or muscle biopsy. Pietro Spitali, associate professor at the Department of Human Genetics, explains: “It’s quick, minimally invasive, and doesn’t depend on how someone feels on the day of testing. If doctors can monitor disease progression through blood, they can tailor treatments more effectively. It also helps researchers evaluate new therapies more quickly, without relying on physical tests that are tiring, subjective, or not always feasible.”
To investigate this potential, LUMC researchers, working closely with the LUMC Biobank, collected blood samples from individuals with Duchenne muscular dystrophy over a ten-year period. They also documented clinical symptoms at each time point for later comparison with blood results. The University of Florida in the United States has also created a similar dataset.
These two separate cohorts made a retrospective study possible. In this type of study, rather than following patients over time, researchers look at previous samples and data to identify trends. The researchers analyzed 702 blood samples from 153 individuals with Duchenne. They used a method that can measure more than 6,600 proteins simultaneously. Biosymmetric analysis facilitated the analysis of data from both centers.
By linking the information from blood proteins to the data in the medical records, the researchers were able to look for patterns. Ikelaar: “We wondered whether the presence of certain proteins could tell us something about key moments in the disease, such as when someone can no longer walk or can no longer use their arms properly.”
Blood proteins as possible biomarkers
The researchers identified hundreds of proteins in the blood of people with Duchenne muscular dystrophy that are linked to disease progression. Some of these proteins were associated with the use of corticosteroids. “Corticosteroids are widely used to help control symptoms and can slow down muscle degeneration. Understanding how these proteins respond to corticosteroid use, helps us distinguish between protein changes caused by the treatment and those caused by the disease progression,” Spitali said.
Other proteins represented motor skills, like walking or arm function. RGMA, ANTXR2, and ART3 were among the few proteins that stood out due to their substantial correlation with the loss of both arm and leg function. Crucially, two sizable, separate patient populations confirmed the findings. This increases the findings’ dependability and raises the possibility that the biomarkers found are generally useful in clinical practice rather than unique to any one group or study environment.
The prestigious scientific journal Nature Communications recently published their research.
Towards more personalized care
This study lays the groundwork for a new method for monitoring Duchenne muscular dystrophy. This method relies not only on physical performance but also on objective measurements of blood proteins. “The goal is to treat patients while they still have muscle mass to maintain,” Spitali says. This usually occurs before the age of eight. However, physical examinations often don’t reveal any deterioration at this age. In fact, growth is progressing in some areas of the body in children. Physical changes are easier to detect later in life, when symptoms are more pronounced and muscle strength is diminishing. However, because most of the muscle has already been wasted by this time, treatments are less successful.
This presents a challenge for researchers testing new drugs and for doctors treating their patients. A response to muscle mass is essential to determine whether a treatment is effective. Blood tests that objectively identify which young individuals are likely to experience remission, even before symptoms appear, could help close this gap. These indicators could help clinicians make more personalized treatment decisions in clinical practice, enabling interventions before key milestones are reached. “With these findings, we are moving closer to truly personalized care for individuals with Duchenne,” Spitali said. “These findings open the door to innovative outcome measures that are less burdensome and more precise.”
Research and treatment for Becker and Duchenne muscular dystrophy
The LUMC offers the sophisticated care required for Duchenne and Becker muscular dystrophy, serving as a national reference center for these disorders. Spieren voor Spieren supports three facilities, including the Children’s Muscle Center at our Willem Alexander Children’s Hospital (WAKZ). It is dedicated to the future, well-being, and health of kids with muscular disorders.
We seek to learn more about the causes of these disorders, how they develop, and how to enhance therapy through both domestic and foreign scientific study. We collaborate closely with other centers of expertise as well. The LUMC is part of the national expertise center for Duchenne and Becker muscular dystrophy, which is also included of Radboudumc and the Kempenhaeghe Center for Neurological Learning and Developmental Disorders.
Read More: Clinical Trials for Duchenne (List of All Researches)
