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Miglustat: a first-in-class enzyme stabilizer for cipaglucosidase alfa for the treatment of late-onset Pompe disease - PubMed

4 hours ago
  • #miglustat
  • #Pompe disease
  • #enzyme replacement therapy
  • Miglustat is a first-in-class enzyme stabilizer used with cipaglucosidase alfa for treating late-onset Pompe disease (LOPD).
  • LOPD is caused by a deficiency of the lysosomal enzyme acid α-glucosidase (GAA), leading to glycogen accumulation in muscles.
  • Enzyme replacement therapy (ERT) with alglucosidase alfa was the first treatment for Pompe disease but has limitations like enzyme instability in blood.
  • Cipaglucosidase alfa, a second-generation ERT, is enhanced with miglustat to improve stability and uptake in target tissues.
  • Clinical studies show miglustat improves cipaglucosidase alfa's efficacy, leading to better functional outcomes and reduced glycogen buildup.
  • Miglustat is administered every two weeks at lower doses for LOPD, resulting in fewer gastrointestinal side effects compared to higher doses used in other diseases.
  • The combination therapy has shown promise in preclinical and clinical trials, improving biomarkers and muscle function in patients.