In Utero Enzyme Replacement for Pompe’s Disease: Are we Entering a New Era in the Treatment of Genetic Disorders?
BACKGROUND AND PURPOSE:
Infantile-onset Pompe’s disease is a lysosomal storage disease
Treatment is with enzyme replacement therapy (ERT) after birth
Children can still be left with irreversible organ damage
Cohen et al. (NEJM, 2022) report the safety and efficacy results of in utero ERT in a fetus with Pompe’s disease
37-year-old woman with a history of three previous pregnancies affected with CRIM (cross-reactive immunologic material)–negative infantile-onset Pompe’s disease
Prenatal diagnosis with chorionic villus sampling confirmed current affected pregnancy
Patient received in utero ERT (Alglucosidase alfa) via umbilical vein as part of an IRB approved phase 1 clinical trial
Initial dose: 24w5d
Subsequent doses: Every 2 weeks through 34w5d (total 5 infusions)
Plasma trough levels of GAA enzyme activity and serum antidrug antibody titers measured at each infusion
No adverse events occurred during the transfusions
Induction of labor: 37w3d
Vaginal delivery: 37w4d
Newborn Outcomes (through 13 months)
Creatine kinase levels: Normal from day 4 (vs typically elevated creatine kinase levels in affected newborns prior to ERT therapy after birth)
No motor deficits detected (gross and fine motor)
In this case report, the patient with CRIM-negative infantile-onset Pompe’s disease who was treated with ERT in utero showed no signs of motor or neurodevelopmental deficits, and cardiovascular function was normal
The authors state
Nondirective counseling for parents of affected pregnancies is critical to ensure informed choices regarding the risk–benefit profile of this new therapy
Our phase 1 clinical trial of in utero ERT for fetuses with genetically confirmed early-onset lysosomal storage diseases will enable the collection of additional safety and efficacy data in a larger cohort
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