New findings suggest a strong association between certain lower extremity biomarkers and measures of clinical function in patients with Duchenne muscular dystrophy.
Krista Vandenborne, PT, PhD, distinguished professor, and chair, department of physical therapy, University of Florida College of Public Health and Health Professions
Krista Vandenborne, PT, PhD
New study results suggest that lower extremity magnetic resonance (MR) biomarkers—particularly those from the proximal muscles—are strongly associated with measures of clinical function in patients with Duchenne muscular dystrophy (DMD).1
Conducted by Krista Vandenborne, PT, PhD, distinguished professor, and chair, department of physical therapy, University of Florida College of Public Health and Health Professions, and colleagues, the investigation concluded that vastus lateralis fat fraction, vastus lateralis MRI T2, and biceps femoris long head MRI T2 biomarkers were the fastest progressing biomarkers over time in a primarily ambulatory cohort of 160 participants (NCT01484678).
“When clinical trials in DMD initially entered the therapeutic development space, it was logical to assume clinical outcome measures would be the most ideal endpoint for trials,” Vandenborne told NeurologyLive. “However, with a number of failed trials, it became clear that there is an unmet need for biomarkers that are sensitive to disease progression in DMD that are both unbiased and non-invasive.”
In addition to MR data acquisition, patients underwent 4 tests of ambulatory function, returning for follow-up data collection at 12, 24, 36, and 48 months. The biomarker values observed by the investigators revealed a nonlinear, sigmoidal trajectory over time, with lower extremity biomarkers foretelling functional performance at both 1 and 2 years later. The magnitude of change in any single MR biomarker over time was linked to the same measurement in clinical function.
The aforementioned vastus lateralis FF, soleus FF, vastus lateralis MRI T2, and biceps femoris long head MRI T2 were the strongest predictors of future loss of function in the cohort, as well as future loss of ambulation.
“The results of this study help clinicians link the degree of muscle pathology in DMD to functional abilities and clinical presentation,” Vandenborne explained. “The data also helps clinicians plan for future changes in disease progression by identifying periods of faster versus slower progression and predictors of milestone events such as loss of ambulation.​”
Vandenborne noted that the strong correlation between MR biomarkers of muscle health to functional outcomes and predicting future clinical milestones, makes them ideal candidates for surrogate outcome assessments in clinical trials. This association allows for them to “help determine whether a drug is effective/ineffective in a shorter time frame, in fewer participants, and with greater certainty,” she said.
Recent additional work from Vandenborne and another study group, published late last year, suggested similar insights can be gleaned by using MRI measures of respiratory muscle quality—including diaphragm and chest wall movement, and accessory respiratory muscle fatty infiltration—to explore the association between disease progression and clinical respiratory function.2
In that study, individuals with DMD (n = 36) had decreased thoracic cavity area compared to the control group (n = 12). Chest wall movement in the anterior-posterior direction during maximal inspirations and expirations was reduced in the DMD group, but only those with maximal inspiratory pressures less than 60% predicted had diaphragm drop during maximal inspirations.
Additionally, muscle fat fraction was high in all 3 expiratory muscles assessed (P <.001), and the degree of fatty infiltration was correlated with the percent predicted maximal expiratory pressures (r =  —0.70; P <.001).
1. Barnard AM, Willcocks RJ, Triplett WT, et al. MR biomarkers predict clinical function in Duchenne muscular dystrophy. Neurology. Published online February 5, 2020. doi: 10.1212/WNL.0000000000009012.
2. Barnard AM, Lott DJ, Batra A, et al. Imaging respiratory muscle quality and function in Duchenne muscular dystrophy. J Neurol. 2019;266(11):2752-2763. doi: 10.1007/s00415-019-09481-z.