Biomarkers and Outcomes in Late-onset Pompe Disease in the Enzyme-replacement Therapy Era

Late-onset Pompe disease (LOPD) is a rare myopathy, genetically inherited in an autosomal recessive pattern, that affects intramuscular glycogen metabolism, due to a deficit in the acid alpha-glucosidase enzyme. The main clinical manifestations encompass proximal muscle motor deficit, as well as diaphragm weakness, which consequently leads to a restrictive respiratory syndrome. Since the approval of enzyme replacement therapy (ERT), the disease prognosis has been markedly improved. Treatment efficiency is usually monitored using generic biomarkers for neuromuscular disease, which lack specificity and are poorly adapted to this particular condition’s evolution. This review aims to provide an overview of the various biomarkers that have been used as outcomes in LOPD research, particularly in studies investigating ERT efficiency. Randomized controlled trials (RCTs) generally rely on outcomes such as forced vital capacity (FVC) and the 6-minute walking test (6MWT). Other emerging biomarkers such as urinary glucose tetrasaccharide (Glc4) and microRNAs have been taken into consideration for assessing disease evolution. Additionally, whole-body muscle magnetic resonance imaging (MRI) and diaphragm ultrasound represent emerging tools for disease follow-up. The anti-drug antibodies (anti-rhGAA) developed with the introduction of ERT are of particular interest, given the lack of consensus regarding their impact on treatment efficacy. Despite substantial progress in biomarker research, challenges persist in identifying specific and sensitive outcomes that correlate with clinical outcomes. This review aims to investigate the existing biomarkers and to look into emerging biomarkers in LOPD.