Both type 1 and type 2a muscle fibers can respond to enzyme therapy in Pompe disease.
Muscle weakness is the main symptom of Pompe disease, a lysosomal storage disorder for which major clinical benefits of enzyme replacement therapy (ERT) have been documented recently. Restoration of skeletal muscle function is a challenging goal. Type 2 muscle fibers of mice with Pompe disease have proven resistant to therapy. To investigate the response in humans, we studied muscle biopsies of a severely affected infant before and after 17 months of therapy. Type 1 and 2a fibers were marked with antibodies, and lysosome-associated membrane protein-1 (Lamp1) was used as the lysosomal membrane marker. Quantitative measurements showed a 2.5-3-fold increase of fiber cross-sectional area of both fiber types during therapy and normalization of the Lamp1 signal in approximately 95% of type 1 and approximately 75% of type 2a fibers. The response of both type 1 and 2a muscle fibers in the patient studied herein corroborates the beneficial effects of enzyme therapy seen in patients with Pompe disease.
Drost
Maarten R
MR
Department of Movement Sciences, Nutrition, Toxicology Research Institute Maastricht, Maastricht University, P.O. Box 616, NL 6200 MD Maastricht, The Netherlands. maarten.drost@bw.unimaas.nl
Schaart
Gert
G
van Dijk
Paul
P
van Capelle
Carine I
CI
van der Vusse
Ger J
GJ
Delhaas
Tammo
T
van der Ploeg
Ans T
AT
Reuser
Arnold J J
AJ
D002675:Child, Preschool; D005260:Female; D006009:Glycogen Storage Disease Type II / Q000473:pathology* / Q000628:therapy*; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D008297:Male; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects* / Q000502:physiology; D018657:Muscle Fibers, Slow-Twitch / Q000187:drug effects* / Q000502:physiology; D000520:alpha-Glucosidases / Q000627:therapeutic use*; D052118:Lysosomal-Associated Membrane Protein 1
D051907:Lysosomal Membrane Proteins; D000520:alpha-Glucosidases; C489116:LAMP1 protein, human; D052118:Lysosomal-Associated Membrane Protein 1