In a medical first, scientists have successfully treated a patient’s genetic condition before they were even born. The novel technique, used to treat the rare and often fatal Pompe disease, was administered to a fetus for the first time ever and has so far proven a success.
Ayla, now 16 months old, is the focus of a case study that reports the safety and efficacy of enzyme-replacement therapy (ERT) for treating Pompe disease in a fetus for the first time. The condition took the lives of two of her siblings – but following in utero ERT and further postnatal treatment, Ayla appears to be developing normally.
“The emergence of a new medical treatment to lift the burden of Pompe disease for this family, and potentially help other families affected by devastating genetic diseases, is both exciting and incredibly satisfying,” Dr Karen Fung-Kee-Fung, the family’s maternal-fetal medicine specialist at the Ottawa Hospital, said in a statement. “We feel very privileged and honored to be a part of this international collaboration to help make this first-in-the-world treatment a reality.”
Pompe disease is an inherited disorder that primarily affects the heart and skeletal muscles. It is rare, affecting approximately one in every 40,000 births. It is caused by mutations in the gene that codes for the enzyme acid alpha-glucosidase (GAA), which breaks down glycogen – a stored form of glucose – in cells. However, in someone with Pompe disease, who has much less GAA, glycogen can accumulate to dangerous levels throughout the body.
When the loss of GAA is total or near-total, such as in Ayla’s case, the condition is described as early onset. Babies born with the condition tend to have enlarged hearts and most will die from cardiac or respiratory complications before the age of one if they don’t receive treatment.
The standard treatment for Pompe disease is ERT administered to newborns via IV infusion. While it can help decrease heart size, improve muscle function, and reduce glycogen accumulation, it can’t fix any organ damage that has already occurred and often triggers an immune response. All of this means that babies treated for Pompe disease after birth are still at risk of death in early childhood, poor muscle tone, and ventilator dependency.
By delivering ERT pre-birth, doctors hope to avoid these outcomes and offer babies and their families a glimmer of hope.
“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,” Dr Tippi MacKenzie, University of California, San Francisco (UCSF) researcher and developer of the protocol, told Gizmodo.
Developed at UCSF, where the treatment is part of an ongoing trial, the protocol delivered to Ayla is a collaboration with the Children’s Hospital of Eastern Ontario (CHEO), The Ottawa Hospital, and Duke University.
Starting at 24 weeks and five days gestation, a total of six ERT infusions were delivered every two weeks until birth. After birth, Ayla continued to receive ERT. Now, at 16 months old, she has normal cardiac and motor function and is meeting developmental milestones.
“When we were having Ayla, we didn't know if she'd be able to walk,” said Zahid Bashir, Ayla’s father. “We didn't know if she'd be able to talk. We didn't know if she'd be able to eat. We didn't know if she'd be able to laugh. So, as she hits each of these milestones, we continue to be amazed at her progress.”
The trial continues, with two more patients with different genetic conditions enrolled. The first gave birth in late October and the second is expected to in early November. Off the back of their initial success with Ayla, the researchers hope the trial will continue to demonstrate the promise of ERT.
“It’s exciting to continue this research, which is an important step in the evolution of fetal therapy, from surgery for anatomic conditions to medical therapies for genetic conditions,” said MacKenzie.
The case study is published in the New England Journal of Medicine.