Researchers identify markers of oculopharyngeal muscular dystrophy progression

Researchers determined deltoid muscle strength to be the top clinical outcome measure when it comes to capturing oculopharyngeal muscular dystrophy progression, according to findings published in Neurology.

“Oculopharyngeal muscular dystrophy (OPMD) is a late-onset, progressive muscle disease. Disease progression is known to be slow, but details on the natural history remain unknown,” Rosemarie H.M.J.M. Kroon, MA, of Radbound University Medical Center in the Netherlands, and colleagues wrote. “We aimed to examine the natural history of OPMD in a large nationwide cohort to determine clinical outcome measures that capture disease progression and can be used in future clinical trials.”

In a nationwide longitudinal cohort study, Kroon and colleagues analyzed data from 43 patients aged 44 to 79 years with OPMD (22 women; mean age at baseline, 60.2 years). Patients and their family members were recruited by their physicians or through the national neuromuscular database (Computer Registry of All Myopathies and Polyneuropathies; CRAMP) in the Netherlands to participate in the study.

Researchers assessed complaints associated with oropharyngeal tasks, such as swallowing, chewing and speaking, as well as limb function by interviewing and clinically examining patients at baseline and at 20 months’ follow up.

The examination identified each patient’s muscle strength, functional capacity and quality of life using fixed dynamometry, Medical Research Council (MRC) grading, maximum bite force and isometric tongue strength, Motor Function Measure (MFM), 10-step stair test, maximum swallowing, chewing and speech tasks and quality of life measures.

Researchers found disease progression was observed in 8 of 18 measures over the course of the study. They saw the highest rate of deterioration in deltoid muscle strength (-27%; range, -17 to -37%), followed by the quadriceps (-14%; range, -6 to -23%), iliopsoas (-12.2%), tongue (-9.9%) and MRC sum score (-2.5%). Additionally, the 10-step stair test (-12.5%), MFM part D1 (-7.1%) and maximum repetition rate of /pa/ (-5.3%) demonstrated substantial reductions (all P < .05).

Kroon and colleagues reported no correlation between disease progression and genotype or disease duration.

Limitations of this study included underestimations of bite force, though that did not impact “the value of the longitudinal data,” according to the researchers, and the inability to complete a third time point during follow-up, which would have enabled “more solid conclusions” regarding the responsiveness of the outcome measures.

“This study shows the feasibility to quantify disease progression in OPMD within 20 months, the time frame of a drug trial. This paves the way for reliable clinical trials in humans,” Kroon and colleagues concluded. “Equally important is that our results show that weakness of the shoulder girdle and lower limb girdle are more sensitive to changes than the oropharyngeal measurements. However, further research is needed to confirm and explain these findings in larger (international) cohorts.