New ultrasound tool may help monitor muscle disease in IOPD
Scientists call noninvasive QMUS 'a window into disease progression'
A new noninvasive imaging tool called quantitative muscle ultrasound, or QMUS, can detect progressive muscle disease in people with infantile-onset Pompe disease (IOPD) who are on enzyme replacement therapy (ERT), according to a small study by U.S. researchers.
The study found that QMUS correlated with functional status and often showed changes in muscle tissue before a decline in motor function. Also, QMUS responses were influenced by ERT dose, the age when such treatment began, and the use of next-generation therapies, the data revealed.
“QMUS is a promising noninvasive tool for monitoring muscle health in patients with IOPD receiving ERT. It may aid in assessing disease progression and treatment efficacy,” the researchers wrote.
Titled “Quantitative muscle ultrasound as a window into disease progression in infantile-onset Pompe disease,” their study was published in the journal Molecular Genetics and Metabolism.
Pompe is marked by progressive muscle weakness due to the harmful buildup of the complex sugar glycogen in muscle cells. It’s caused by a genetic deficiency of the enzyme acid alpha-glucosidase, known as GAA.
Small study tested muscle ultrasound in patients on long-term ERT
Currently, ERT — which supplies patients with a healthy version of GAA to help clear excess glycogen from muscle cells — is standard practice for Pompe treatment.
Monitoring Pompe progression relies on a combination of tests, including physical examination, assessments of motor and lung function, and blood and urine tests.
Imaging tools such as muscle MRI have helped assess muscle involvement, especially in cases of extensive muscle damage, including fatty replacement and swelling. Still, their use can be expensive and time-consuming, and sedation is often needed for infants and young children.
QMUS is an alternative to muscle MRI, and conversely, is portable and less expensive. Importantly, the researchers noted, it’s more sensitive to subtle muscle changes, and provides information on muscle thickness and structural abnormalities.
The goal of this study, by researchers at Duke University in North Carolina, was to evaluate the tool’s ability to monitor muscle disease in IOPD patients undergoing long-term ERT. This work was partly funded by a grant from Sanofi, which markets the ERTs Lumizyme (alglucosidase alfa) and Nexviazyme (avalglucosidase alfa).
In total, eight IOPD patients were involved in the study. They had started ERT at a median age of 7 weeks, ranging from 5 days to 3.5 months. Yearly QMUS assessments began at a median age of 9.5 years — with a range of 7 months to 21 years.
Using QMUS, the team measured muscle echointensity, or EI, which is the brightness of muscle tissue on ultrasound images. EI values greater than 50 were considered abnormal, indicating disease-related changes in muscle tissue, including increased scarring and fatty infiltration.
 QMUS often revealed muscle changes before motor function decline
All of the patients showed abnormal muscle EI values consistent with IOPD-related muscle disease in at least one muscle group. QMUS findings also showed differences in EI values across patients, within muscle groups within the same patients, and within the same muscle groups over time.
In all but one patient, EI values were significantly higher in the lower body muscles than in the upper body, the data showed. In particular, the quadricep muscles in the upper leg and the tibialis anterior muscles in the lower leg generated the highest EI values, “aligning with the pattern of muscle weakness commonly observed in IOPD,” the team noted.
Higher total EI scores correlated with lower functional mobility, as indicated by the Gross Motor Function Measure (GMFM), but the difference didn’t reach statistical significance. Even so, patients with the higher EI scores had the most severe muscle disease, with the highest three EI values coming from patients who used wheelchairs, the data showed.
Our findings … [reinforce] that imaging biomarkers … [seen with imaging tool] may precede clinical weakness and could serve as early predictors of disease progression.
QMUS often revealed muscle changes before a decline in motor function, as indicated by GMFM scores or distance walked in six minutes, according to the researchers. Moreover, QMUS changes over time were influenced by ERT dose, age at ERT start, and the use of the next-generation ERTs.
“Our findings are consistent with prior MRI data, reinforcing that imaging biomarkers like EI may precede clinical weakness and could serve as early predictors of disease progression,” the team wrote.
As study limitations, the team noted the small number of participants, and that these patients had only two or three QMUS assessments over time, thus “limiting the ability to fully characterize muscle trajectory or detect statistically robust trends over a longer period of time.”
“Future research should focus on addressing key knowledge gaps, such as establishing normal EI cutoffs by studying healthy pediatric populations, optimizing ERT dosing strategies, and exploring the long-term predictive value of EI in relation to muscle function,” the researchers wrote.
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