Toddler treated for genetic condition since they were a fetus

Delivering an enzyme-replacement therapy to a fetus via its umbilical cord prevented a child from developing symptoms of a rare genetic condition, in a first-of-its-kind clinical trial.

The child, who is now 16 months old, was born to parents who had previously lost two children to Pompe disease, which, without treatment, is typically fatal before the age of two due to effects on the heart and skeletal muscle. It is one of more than 50 genetically inherited lysosomal storage disorders. People affected by the condition are unable to create the enzyme acid alpha-glucosidase, which normally breaks down glycogen into glucose in the lysosomes of our cells. For the first time, prenatal therapy to replace the missing enzyme was used to treat this disease in utero, preventing heart damage, which often starts prenatally.

Co-lead author Dr Jennifer Cohen from Duke University School of Medicine, North Carolina said: 'From our long-standing work at Duke treating patients with Pompe disease, we know first-hand the critical importance of earlier initiation of treatment. Our ability to offer a new treatment opportunity to this family and potentially change the course of this difficult disease has made this collaboration and project ground-breaking'.

Enzyme replacement therapy has been used to treat Pompe disease and other genetically inherited lysosomal storage disorders before, but this is the first time it has been used before birth. The drug was administered to the fetus into the umbilical vein via injection through the abdomen of the mother at two-week intervals from the 24th week of gestation.

When born at 37 weeks, the child did not exhibit typical symptoms of Pompe disease, such as motor deficits, loss of muscle tone, or heart disease, showing that the treatment was effective. Now 16 months old, the patient continues to receive enzyme replacement therapy every two weeks and has reached all normal developmental milestones, including walking.

The parents of this child previously had two children die of Pompe disease, and had experienced multiple pregnancy losses. Understanding the family history of symptom onset in these children helped identify this fetus as a good candidate for the clinical trial.

Professor Simon Waddingham, University College London, who was not involved in this study, told STAT that this case 'is another example of fetal therapy for an inherited genetic disease, where treating as early as possible in life may have substantial benefits.'

Despite being an effective treatment for this disease, enzyme replacement therapy is not a cure, and this child will be required to continue treatment throughout her life, as the authors outlined in the paper published in New England Journal of Medicine.

Corresponding author Dr Tippi MacKenzie, a paediatric and fetal surgeon at the University of California, San Francisco, told MIT Technology Review: 'We're hoping it opens the way … for other medical therapies for fetuses with genetic diseases,' adding 'There's so much more data we need to understand the safety and feasibility of prenatal gene therapy'. Further discussions took place around the ethics of trials involving fetuses and pregnant women before this became possible however, she warned.