P.17.4 Magnetic Resonance Imaging (MRI) to evaluate the effect of enzyme replacement therapy in Late Onset Pompe Disease (LOPD)

Abstract

Pompe disease is a rare, progressive and often fatal neuromuscular disorder resulting from mutations in the gene for acid alpha-glucosidase (GAA), an enzyme necessary to degrade glycogen. The deficiency or dysfunction of the GAA enzyme leads to lysosomal glycogen accumulation in multiple tissues and results in cardiac and skeletal muscle dysfunction. Glycogen content may vary between muscle groups and in regions of the same muscle. Most importantly, glycogen content may change during the course of the disease. Enzyme replacement therapy (ERT) is the only FDA approved treatment for Pompe disease. However, translation from preclinical to clinical studies is challenged by the lack of reliable, noninvasive outcome measures suitable for repeated evaluations. Effect of treatment is commonly measured by muscle glycogen clearance using biochemical assays, which rely on muscle biopsy. In this study, we used Magnetic Resonance Imaging (MRI) of the thigh and lower leg muscles to evaluate the effect of 12 and 24 weeks of ERT in individuals affected by Late Onset Pompe Disease (LOPD) (n = 4; age 35–50). Maximum cross-sectional area (CSAmax) – an index of muscle mass – increased in average by 1.16- and 1.09-fold at 12 weeks, and by 1.13- and 1.09-fold at 24 weeks in the lower and upper legs respectively. In addition, we studied the MR proton traverse relaxation time (T2) – an index of muscle damage and edema – by applying a mono exponential decay equation to four echo times (TE). At 24 weeks, T2 values reduced by 1.20- and 1.10-fold in the lower and upper legs, respectively. These data demonstrate an increase in CSAmax associated accompanied by a reduction of T2 value, which may suggest a reduction of glycogen accumulation and an increase of contractile myofibers. In support of this hypothesis, biochemical assay from muscle biopsy specimens showed a reduction of glycogen concentration by 2.21-fold at week 24 compare to baseline.