For the first time, doctors are treating a fatal genetic disease before birth

A toddler is thriving after doctors in the US and Canada used a new technique to treat her before she was born for a rare genetic disease that killed two of her sisters.

Ayla Bashir, a 16-month-old from Ottawa, Ontario, is the first child treated as a fetus for Pompe disease, an inherited and often fatal disorder in which the body fails to produce some or all of a vital protein.

Today, she is an active, happy girl who has reached her developmental milestones, according to her father Zahid Bashir and mother Sobia Qureshi.

“She’s a normal little 1½-year-old who keeps us on our toes,” Bashir said. The couple previously lost two daughters, Zara, 2½, and Sarah, 8 months, to the disease. A third pregnancy was terminated because of the disorder.

IN case study published on Wednesday in New England Journal of Medicine, doctors describe an international collaboration during the COVID-19 pandemic that led to the treatment that may have saved Isla’s life—and expanded the field of potential fetal therapies. The outlook for Isla is promising but uncertain.

“There is a glimmer of hope that we can treat them in the womb instead of waiting until the damage is already well established,” said Dr. Karen Fung-Kee-Fung, a maternal-fetal medicine specialist at The Ottawa Hospital who provided treatment and gave birth to Isla.

Fung-Kee-Fung was following a new treatment plan 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, who shared her research after the pandemic prevented Isla’s mother to travel for care.

“We were all motivated to make this happen for this family,” McKenzie said.

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Doctors have been treating fetuses before birth for three decades, often with surgeries to repair birth defects like spina bifida. And they have transfused blood to fetuses through the umbilical cord, but no drugs. In this case, the crucial enzymes were delivered through a needle inserted through the mother’s abdomen and directed into a vein in the umbilical cord. Ayla received six bi-weekly infusions starting at around 24 weeks gestation.

“The innovation here wasn’t the drug and it wasn’t access to the fetal circulation,” said Dr. Pranesh Chakraborty, a metabolic geneticist at the Children’s Hospital of Eastern Ontario who has cared for Ayla’s family for years. “Innovation was healing earlier and healing in the womb.”

The unusual partnership also included experts from Duke University in Durham, North Carolina, which leads research into Pompe disease, and the University of Washington in Seattle.

Babies with Pompe disease are often treated soon after birth with replacement enzymes to slow the devastating effects of the disease, which affects fewer than 1 in 100,000 newborns. It is caused by mutations in a gene that produces an enzyme that breaks down glycogen, or stored sugar, in cells. When this enzyme is reduced or eliminated, glycogen builds up dangerously throughout the body.

In addition, the most severely affected babies, including Ayla, have an immune condition in which their bodies block the infused enzymes, ultimately stopping the therapy from working. The hope is that treating Ayla early will reduce the severity of this immune response.

Babies with Pompe disease have feeding problems, muscle weakness, lethargy, and often severely enlarged hearts. Untreated, most die of heart or respiratory problems within the first year of life.

In late 2020, Bashir and Qureshi learned they were expecting Ayla and that prenatal tests showed she also had Pompe disease.

“It was very, very scary,” Qureshi recalls. Besides the dead girls, the couple has a son, Hamza, 13, and a daughter, Maha, 5, who were not affected.

Both parents carry the recessive gene for Pompe disease, meaning there is a 1 in 4 chance that the baby will inherit the disease. Bashir said their decision to continue with additional pregnancies was driven by their Muslim faith.

“We believe that what will come our way is part of what is meant or intended for us,” he said. They have no plans for more children, they said.

Chakraborty had learned of Mackenzie’s early-stage trial testing the enzyme therapy and thought early treatment could be a solution for the family.

The treatment could be “potentially very important,” said Dr. Brendan Lanpher, a medical geneticist at the Mayo Clinic in Rochester, Minnesota, who was not involved in the study.

“It’s a progressive disease that builds up over time, so every day that the fetus or baby has it, they build up more of the material that affects the muscle cells.”

Still, it’s too early to know whether the protocol will become an accepted treatment, said Dr. Christina Lamm, interim medical director of biochemical genetics at the University of Washington and Seattle Children’s Hospital in Seattle.

“It’s going to take some time before we can really establish evidence that definitively shows that outcomes are better,” she said.

Isla receives drugs to suppress her immune system and weekly enzyme infusions that take five to six hours — a growing challenge for a wiggly toddler, her mother said. Unless a new treatment comes along, Isla can expect to continue the infusions for life. She is developing normally – for now. Her parents say that every milestone, such as when she started crawling, is especially precious.

“It’s surreal. It amazes us every time,” Qureshi said. “We are so blessed. We were very, very blessed.”

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