A toddler girl is flourishing after receiving treatment for a rare genetic disease. In a first for this disease, she received that treatment before she was even born.
Sixteen-month-old Ayla has infantile-onset Pompe disease — a genetic disorder that can cause organ damage that begins before birth. Babies born with Pompe have enlarged hearts and weak muscles. If left untreated, most infants die before they turn 2. Treatment typically begins after birth, but that tactic doesn’t prevent the irreversible, and potentially deadly, organ damage that happens in utero.
Ayla received treatment while still in the womb as part of an early-stage clinical trial. Today, the toddler has a normal heart and is meeting developmental milestones, including walking. Her success is a sign that prenatal treatment of the disease can stave off organ damage and improve babies’ lives, researchers report November 9 in the New England Journal of Medicine.
“It’s a great step forward,” says Bill Peranteau, a pediatric and fetal surgeon at the Children’s Hospital of Philadelphia who wasn’t involved in the work.
Infantile-onset Pompe disease is a rare condition that affects fewer than 1 out of 138,000 babies born globally. It’s caused by genetic changes that either reduce levels of an enzyme called acid alpha-glucosidase, or GAA, or prevent the body from making it at all.
Inside cellular structures called lysosomes, GAA turns the complex sugar glycogen into glucose, the body’s main source of energy. Without GAA, glycogen accumulates to dangerously high levels that can damage muscle tissue, including the heart and muscles that help people breathe.
While some people can develop Pompe disease later in life or have a less severe version that doesn’t enlarge the heart, Ayla was diagnosed with the most severe form. Her body doesn’t make any GAA. Replacing the missing enzyme through an infusion can help curb glycogen buildup, especially if treatment starts soon after birth (SN: 4/26/04).
Early studies in mice suggested that treatment before birth showed promise at controlling a Pompe-like disease. So pediatric geneticist Jennifer L. Cohen of Duke University School of Medicine and colleagues launched an early-stage clinical trial covering Pompe and seven similar conditions, broadly called lysosomal storage diseases.
The team began treating Ayla by infusing GAA through the umbilical vein when her mother was 24 weeks pregnant. Her mother received a total of six infusions, one every two weeks. After birth, the medical team has been treating Ayla with now-weekly infusions, and she will continue to need treatment throughout her life.
The therapy was safe for both mother and child, Cohen says. But until more patients are treated and monitored in the trial, it’s unclear whether this prenatal enzyme replacement is always a safe and effective option. So far, two other patients with other lysosomal storage diseases have received treatment in the trial, but it’s too early to know how they’re faring.
Researchers are also exploring in utero therapies for other rare genetic diseases, including the blood disorder alpha thalassemia. And in 2018, researchers described three children who were successfully treated for a sweating disorder before they were born.
Such approaches have the potential to treat other rare diseases in the future, Peranteau says. But it will be important to first show that any newly developed treatments are safe and work when given after birth before trying them in utero.
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For now, it’s unclear how Ayla and other treated patients will fare over the long term, Cohen says. “We’re cautiously optimistic, but we want to be careful and be monitoring throughout the patient’s life. Especially those first five years, I think, are going to be critical to see how she does.”