Gene Therapy Used for First Time to Correct Fatal Illness Before Birth

THURSDAY, Nov. 10, 2022 (HealthDay News) – Doctors are hopeful that an innovative treatment performed before birth may help children born with the rare genetic, and often fatal, condition called Pompe disease.

A thriving Canadian toddler is evidence that treatment while still in the womb offers better outcomes.

Doctors from the United States and Canada published a case study Nov. 9 in the New England Journal of Medicine detailing their efforts to save the baby. Her parents lost two other daughters to the condition, the Associated Press reported.

The new treatment may not only have saved Ayla Bashir, now 16 months old, but also have added to potential fetal therapies.

"It holds a glimmer of hope for being able to treat them in utero instead of waiting until damage is already well-established," Dr. Karen Fung Kee Fung told the AP. She is a maternal-fetal medicine specialist at The Ottawa Hospital who gave the treatment and delivered Ayla.

The treatment plan was developed by Dr. Tippi MacKenzie, a pediatric surgeon and co-director of the Center for Maternal-Fetal Precision Medicine at the University of California, San Francisco.

MacKenzie shared her research with Fung Kee Fung when the COVID pandemic prevented the Bashir family from traveling for care, the AP reported.

"We were all motivated to make this happen for this family," MacKenzie told the AP.

Pompe disease is caused by mutations in a gene that makes an enzyme that breaks down glycogen in cells. That causes glycogen to build up throughout the body.

The condition is typically treated soon after birth with replacement enzymes. Some of the babies also are born with an immune condition that blocks the infused enzymes, so the therapy eventually stops working, according to the report.

Pompe disease affects about 1 in 40,000 births, according to the U.S. National Institute of Neurological Disorders and Stroke. Left untreated, most babies with Pompe die of heart or breathing problem in their first year of life.

Ayla was treated with the enzymes through a needle inserted into her mother's abdomen and then guided into an umbilical cord vein, the AP reported. This began at 24 weeks' gestation and continued for six biweekly infusions.

Ayla's doctors and her family are hopeful that the early treatment will limit the problematic immune response caused by Pompe, though her long-term outlook is unknown.

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

Ayla continues to receive long weekly enzyme infusions and drugs that suppress her immune system. She will need to do so for life.

She's also active, happy and developmentally on track, Ayla's parents said.

"She's just a regular little 1½-year-old who keeps us on our toes," her father, Zahid Bashir, told the AP.

"It's surreal. It amazes us every time," said Ayla's mother, Sobia Qureshi. "We're so blessed. We've been very, very blessed."

The family has a 13-year-old son, Hamza, and 5-year-old daughter Maha, who are not affected by the disease. They lost daughters Zara, who was 2½, and Sara, who was 8 months, to Pompe disease. The family also terminated another pregnancy because of the condition.

The parents both carry a recessive gene for Pompe disease, giving them a 1 in 4 chance of a fetus being affected in each pregnancy. Their Muslim faith led them to continue to try to have more children.

When the couple learned they were expecting Ayla, they also learned she had the disease.

"It was very, very scary," Qureshi said to the AP.

While doctors have treated fetuses with surgeries to repair birth defects such as spina bifida or with blood transfusions through the umbilical cord for many years, this is the first in which critical medicines were delivered.

This effort also involved experts at Duke University in Durham, N.C., and the University of Washington in Seattle.

The researchers said it's still too early to tell if this procedure will eventually become accepted treatment for the disorder.

More information

The U.S. National Institute of Neurological Disorders and Stroke has more on Pompe disease.

SOURCE: Associated Press, Nov. 9, 2022