AAV9-Mediated Gene Therapy for Infantile-Onset Pompe's Disease

N Engl J Med. 2025 Jun 26;392(24):2438-2446. doi: 10.1056/NEJMoa2407766.

Abstract

Four patients with infantile-onset Pompe's disease received a single intravenous injection of an adeno-associated virus serotype 9 vector carrying codon-optimized complementary DNA encoding human acid α-glucosidase (GAA) (dose, 1.2 × 1014 vector genomes per kilogram of body weight). One patient was withdrawn from the study and subsequently died. The other patients had improvement in cardiac outcomes and motor function over a 52-week observation period. Anti-GAA antibodies were not detected in any of the patients during the observation period. Respiratory tract infections were the most common adverse events. (Funded by the National Natural Science Foundation of China and National High Level Hospital Clinical Research Funding; Chinese Clinical Trial Registry number, ChiCTR2200063229.).

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Child, Preschool
  • Dependovirus* / genetics
  • Dependovirus* / immunology
  • Follow-Up Studies
  • Genetic Therapy* / adverse effects
  • Genetic Therapy* / methods
  • Genetic Vectors* / administration & dosage
  • Genetic Vectors* / adverse effects
  • Glycogen Storage Disease Type II* / genetics
  • Glycogen Storage Disease Type II* / therapy
  • Humans
  • Infant
  • Injections, Intravenous
  • Male
  • Respiratory Tract Infections / etiology
  • Treatment Outcome
  • alpha-Glucosidases* / genetics
  • alpha-Glucosidases* / immunology

Substances

  • alpha-Glucosidases
  • GAA protein, human