In a first, doctors successfully treated a rare genetic disease before birth

The toddler, now 16 months old, is growing up healthy.
Ayesha Gulzar

In a medical first, doctors successfully treated a fetus for a fatal genetic condition called Pompe disease, according to a press release published by the University of California, San Francisco. The enzyme needed to treat the condition was delivered through a needle inserted through the mother's abdomen and guided into a vein in the umbilical cord.

The baby, Ayla Bashir, is the focus of the case study and is now 16 months old. She is an active, happy girl who has met her developmental milestones, according to her parents.

Alya was identified with severe Pompe disease while she was still a fetus. She is her parents' fifth child but only the third to survive. The other two, Zara and Sara, died of the same disease.

A rare genetic condition

Pompe is a rare genetic condition that affects about 1 in 40,000 births. It is caused by mutations in a gene that makes a crucial enzyme called acid alpha-glucosidase (GAA). This enzyme breaks down glycogen, or stored sugar, in cells.

When the enzyme is reduced or eliminated, glycogen builds up dangerously throughout the body. This build-up causes all several health problems but especially damages the heart and skeletal muscles.

The condition is typically treated with replacement enzyme therapy (ERT) soon after birth. However, some babies, including Alya, are born with an immune condition that blocks the infused enzymes, so the therapy eventually stops working. The hope is that Ayla's early treatment will reduce the severity of that immune response.

"The rationale for giving ERT before birth is to prevent the onset of organ damage, to get the enzyme into the [central nervous system] prior to closure of the blood-brain barrier, and to avoid an immune response to the missing protein," said senior study author Tippi MacKenzie, UCSF researcher and developer of the team's protocol in a statement.

To treat Alya before birth, researchers from UCSF teamed up with doctors at the Children's Hospital of Eastern Ontario (CHEO) in Canada. They delivered the enzyme through a needle inserted through the mother's abdomen and guided into a vein in the umbilical cord. The treatment began at 24 weeks gestation and continued for six biweekly infusions.

"The innovation here wasn't the drug, and it wasn't accessing the fetal circulation," said Dr. Pranesh Chakraborty, a metabolic geneticist at Children's Hospital of Eastern Ontario, who has cared for Ayla's family for years. "The innovation was treating earlier and treating while still in utero."

Upon delivery, Alya's heart was normal; at 16 months, she is meeting all of her developmental milestones on time. There's also evidence that her body is more tolerant towards the therapy than it would typically be, compared to how her siblings responded to it. Ayla continues to get weekly infusions of enzyme therapy to maintain her development.

Altering the course of genetic conditions

Researchers are now recruiting other families with pregnancies where the fetus has been identified as being affected with Pompe disease or similar genetic disorders.

Doctors hope that their experience may pave the way for fetal treatments that could alter the course of a variety of severe genetic diseases and prevent the need for lifelong medical care.

The study paper was published in The New England Journal of Medicine.

Study Abstract:

Patients with early-onset lysosomal storage diseases are ideal candidates for prenatal therapy because organ damage starts in utero. We report the safety and efficacy results of in utero enzyme-replacement therapy (ERT) in a fetus with CRIM (cross-reactive immunologic material)–negative infantile-onset Pompe’s disease. The family history was positive for infantile-onset Pompe’s disease with cardiomyopathy in two previously affected deceased siblings. After receiving in utero ERT and standard postnatal therapy, the current patient had normal cardiac and age-appropriate motor function postnatally, was meeting developmental milestones, had normal biomarker levels, and was feeding and growing well at 13 months of age.

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