For the first time, doctors treated a fetus for a severe form of a rare genetic disease. To combat the condition, which, untreated, usually causes death before age two, the medical team piped an enzyme through the umbilical cord to the fetus in the womb.
Today, the child, named Ayla, is 16 months old and developing normally, STAT News’ Andrew Joseph reports. Every week, she receives medication with an enzyme that her body doesn’t produce itself.
“We’re cautiously optimistic, but we want to be careful and be monitoring throughout the patient’s life,” Jennifer Cohen, a pediatric geneticist at Duke University, says to Science News’ Erin Garcia de Jesús. “Especially those first five years, I think, are going to be critical to see how she does.”
Cohen and her colleagues published a case study on Ayla last week in the New England Journal of Medicine. It is “an essential proof-of-concept work” and “a cornerstone to better understanding… the benefit of enzyme therapy prenatally,” Yin-Hsiu Chien, a medical geneticist at National Taiwan University Hospital who did not contribute to the research, tells Science’s Jocelyn Kaiser.
Ayla has infantile-onset Pompe disease, a condition that fewer than 1 in 100,000 babies have, according to STAT News. With Pompe, low levels or the lack of a certain enzyme leads to the buildup of a sugar called glycogen. This, in turn, causes muscle weakness and an enlarged heart. Two of Ayla’s older siblings died when they were 2 years old and 8 months old from the same condition, per the New York Times’ Gina Kolata.
Doctors can treat diseases like Pompe by giving babies the enzymes their bodies don’t produce. But infantile-onset Pompe disease starts irreversibly damaging muscles before the baby is born, per the Times.
Doctors have previously conducted surgeries in the womb and given fetuses blood transfusions, writes Jonel Aleccia of the Associated Press (AP). So, Cohen and her colleagues decided to try enzyme replacement therapy in utero and began a clinical trial in San Francisco.
Ayla’s parents, who live in Canada, were unable to travel to San Francisco due to the Covid-19 pandemic, per the Times. But doctors found a way to administer the treatment in Canada, which began when Ayla’s mother was 24 weeks pregnant. They delivered six doses of the enzyme, with each dose received two weeks after the previous dose.
Since then, Ayla has been developing normally, has no sign of the heart problems seen in babies with Pompe and learned to walk at 11.5 months, just like an average child, per Science.
Meanwhile, the ongoing clinical trial will use enzymes to treat fetuses with eight types of lysosomal storage diseases such as Pompe, per Science. Two additional fetuses have received treatment so far, according to the publication.
The trial will also determine the risks and benefits of the treatment, Tippi MacKenzie, a pediatric and fetal surgeon at the University of California, San Francisco, and one of the leaders of the trial, tells STAT News.
“It’s going to take some time to really be able to establish the evidence to definitively show that the outcomes are better,” Christina Lam, a physician at Seattle Children’s Hospital who wasn’t involved in the research, tells the AP.
Doctors knew to look for Pompe in Ayla before she was born due to her family’s history, but most kids with Pompe are diagnosed after birth, notes STAT News. This treatment would only benefit patients whose disease was detected earlier. But for other families with a history of genetic diseases, Ayla’s case could provide some hope, STAT News reports.
Bill Peranteau, a pediatric and fetal surgeon at the Children’s Hospital of Philadelphia who didn’t contribute to the research, tells Science News that the promising results from Ayla’s treatment so far are “a great step forward.”