Growth Factor Levels May Help Track Progression of Adult-onset Pompe Disease, Study Suggests

Measuring the blood levels of the platelet-derived growth factor BB (PDGF-BB) allows researchers to differentiate between patients with adult-onset Pompe disease and those without the disease, and between patients with and without symptoms, a study reports.

These findings suggest that monitoring PDGF-BB could help track disease progression and determine when to start treatment before muscle degeneration is apparent.

The study, “PDGF-BB serum levels are decreased in adult onset Pompe patients,” appeared in the journal Scientific Reports.

In patients with adult-onset Pompe, subtle changes such as abnormalities in posture or walking pattern may not be associated with general motor dysfunction. Asymptomatic patients are currently assessed with muscle function tests to detect changes in motor performance that could lead to them starting treatment. However, muscle degeneration may have already begun without causing significant changes in motor function.

Aiming to find a biomarker of muscle degeneration, a team at Universitat Autònoma de Barcelona in Spain analyzed the serum levels of growth factors related to muscle fibrosis (scarring), degeneration, and inflammation in patients with adult-onset Pompe and in controls. Their study is part of an ongoing open-label trial (NCT01914536) in this patient population.

To determine a possible correlation between growth factor levels and clinical status, the 37 patients underwent muscle function tests, spirometry to assess lung function, and quantitative muscle magnetic resonance imaging (qMRI). Muscle function tests included the six-minute walking test, time to walk 10 meters, timed up-and-go test, time to climb up and down four steps, and the 20 item motor function measure tool.

Patient-reported outcome measures were also collected, which included a measure of activity limitations called ACTIVLIM, the Individualized Neuromuscular Quality of Life Questionnaire, and the Short Form Health Survey (SF-36).

Of the 37 patients, 29 were symptomatic (18 women, mean age of 51 years) — meaning they either had muscle weakness or impaired pulmonary function — while eight were asymptomatic (four women, mean age of 21 years). Twenty-three symptomatic patients were being treated with enzyme replacement therapy (ERT) at the study’s start. Five of the asymptomatic patients had high levels of liver enzymes/creatine kinase, a marker of muscle disease, and three had a family history of Pompe disease.

Compared with controls — including a group of young individuals to account for the age difference between symptomatic and asymptomatic patients — people with Pompe had significantly lower serum levels of PDGF-BB and transforming growth factor beta1 (TGF-β1), but higher levels of PDGF-AA and connective tissue growth factor.

In the Pompe patients, levels of PDGF-BB were significantly lower in symptomatic than in asymptomatic patients, suggesting a correlation with disease progression, according to the scientists. In contrast, the levels of the other growth factors did not differ between these two groups.

A subsequent analysis revealed that the serum levels of PDGF-BB enabled the prediction of which patients were symptomatic and which were asymptomatic, based on a cutoff value of 1.97 nanograms per milliliter.

“Therefore, patients with lower values than the cut-off level (1.97 ng/ml) had a higher probability of being asymptomatic. Sensitivity and specificity were 75% and 76% respectively,” the researchers wrote.

However, no significant correlation was found between PDGF-BB serum concentration and the results of the muscle function tests, spirometry, patient-reported outcomes, and qMRI.

Because PDGF-BB seems to play a role in muscle regeneration, the team then evaluated serum levels of this growth factor in different types of muscular dystrophy with increased regeneration. This showed that the levels of PDGF-BB were higher in patients with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) than in controls.

PDGF-BB levels were lower in patients with Pompe than in those with DMD, BMD and facioscapulohumeral muscular dystrophy, suggesting different underlying mechanisms of muscle fiber degeneration, according to the researchers.

“Our results suggest that decreasing levels of PDGF-BB in asymptomatic patients should prompt us to tighten the follow-up of the patient, repeating muscle and respiratory function tests in order to consider starting ERT before muscle degeneration becomes irreversible,” they wrote.