Morphological changes in muscle tissue of patients with infantile Pompe's disease receiving enzyme replacement...

Area of Science:

• Biochemistry
• Genetics
• Pediatrics

Background:

• Pompe's disease (glycogen storage disease type II) is a rare, autosomal recessive myopathy.
• It results from a deficiency in the enzyme lysosomal alpha-glucosidase.
• Enzyme replacement therapy (ERT) is a promising treatment approach.

Purpose of the Study:

• To evaluate the effects of recombinant human alpha-glucosidase on muscle tissue morphology in infants with Pompe's disease.
• To assess the dose-dependent response and treatment duration for ERT.

Main Methods:

• Four infants with infantile Pompe's disease received ERT with recombinant human alpha-glucosidase derived from rabbit milk for 72 weeks.
• Muscle tissue morphology was assessed before and after treatment.
• Enzyme dosage was escalated from 15-20 mg/kg to 40 mg/kg.

Main Results:

• Initial improvements in vascular endothelium and peripheral nerves were observed after 12 weeks at lower doses.
• After 72 weeks with higher doses (40 mg/kg), a reduction in lysosomal glycogen storage was noted.
• Substantial improvement in muscle architecture was seen in the least affected patient, indicating dose and timing dependency.

Conclusions:

• Intravenous recombinant human alpha-glucosidase shows potential for improving muscle morphology in infantile Pompe's disease.
• Treatment efficacy is influenced by the initial degree of glycogen storage and muscle pathology.
• Initiating ERT before irreversible muscle damage is crucial for optimal outcomes.