A report published in the New England Journal of Medicine describes enzyme replacement therapy (ERT) in utero as a treatment for Pompe disease.
According to the researchers, the patient, who is now a young girl, is doing well. Her parents had previously had children with the same disorder who died.
“This treatment expands the repertoire of fetal therapies in a new direction,” says Tippi MacKenzie, co-author of the report. “As new treatments become available for children with genetic conditions, we are developing protocols to apply them before birth.”
MacKenzie co-directs the UCSF Center for Maternal-Fetal Precision Medicine, and directs the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research.
Pompe disease is caused by mutations in a gene that produces acid alpha-glucosidase. With limited amounts of this enzyme, dangerous amounts of glycogen build up in the body. Babies with infantile-onset disease often have enlarged hearts and die by two years of age.
Estimated to occur in one in 40,000 births, this condition is one of several early-onset lysosomal storage disorders. Patients with these diseases “are ideal candidates for prenatal therapy because organ damage begins in the womb,” the researchers note.
Screening of newborns can lead to early initiation of recombinant enzyme therapy, “but this approach does not completely prevent irreversible organ damage,” the authors note.
The patient in the new report received six prenatal enzyme replacement therapy treatments at Ottawa Hospital in Canada and is receiving postnatal enzyme therapy at CHEO, a pediatric hospital and research center in Ottawa.
The girl, 16 months old, is doing well with normal heart and motor function
The researchers administered alglucosidase alfa through the umbilical vein. They gave the first infusion to the fetus at 24 weeks and 5 days of gestation. They continued to administer infusions at two-week intervals until 34 weeks and 5 days of gestation.
Patients with Pompe disease can usually be clinically diagnosed between 3 and 6 months of age, says study co-author Paul Harmatz, MD, of UCSF. With newborn screening, the disease can be diagnosed within 1 week. But intervening before birth may be optimal, Harmatz points out.