This groundbreaking treatment could have a huge impact in the future for families who carry rare genetic diseases.
Trials for In-Utero Genetic Disorder Treatments
The type of treatment researchers at UCSF have focused on for the past few years is something called enzyme replacement therapy. It’s usually given after a baby is born. Researchers though questioned whether the treatment could be used before babies were born when they are still in utero. UCSF’s treatment focuses on genetic diseases referred to as “early-onset lysosomal storage diseases.” These are metabolic diseases where the body isn’t able to break down certain harmful substances due to inherited enzyme deficiencies. As a result, babies are often born with abnormalities in their major organs, including the brain, skin, heart, skeleton, and nervous system. The Food and Drug Administration (FDA) gave UCSF approval for a phase 1 clinical trial to treat eight different lysosomal storage diseases with enzyme replacement therapy in utero. In November 2022, The New England Journal of Medicine published results for their first case study. It’s the inspiring story of an infant with a lysosomal storage disease called Pompe disease. That baby is now a thriving toddler thanks to the in-utero fetal therapy from UCSF. “This treatment expands the repertoire of fetal therapies in a new direction,” co-senior and corresponding author of the study Tippi MacKenzie, MD, says in a press release. “As new treatments become available for children with genetic conditions, we are developing protocols to apply them before birth.”
Success for Toddler Treated in Utero
The toddler described in The New England Journal of Medicine’s case study is named Ayla. She’s the daughter of Zahid and Sobia Bashir, a couple from Canada who previously endured the unimaginable loss of two children. They both passed away from complications of Pompe disease. It was when the couple was pregnant with Ayla—also diagnosed with Pompe disease—that they heard about the innovative new treatment coming out of UCSF. The only problem was it was during the height of the pandemic, and the couple lived in Canada. Thankfully, UCSF was able to coordinate remotely with Sobia Bashir’s doctors at The Ottawa Hospital and share their treatment protocol with them. Ayla received six enzyme replacement treatments prenatally, and she continues to receive treatment at CHEO, a pediatric hospital in Ottawa. The result? Ayla is now a healthy, thriving toddler. “When we were having Ayla, we didn’t know if she’d be able to walk,” Zahid Bashir says in UCSF’s press release. “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.”
What is Pompe Disease?
Part of the reason UCSF’s in-utero treatment was so helpful in Ayla’s case is because of the genetic disorder she and her siblings had, Pompe disease. It can progress very quickly, even before a baby is born. Pompe disease is a very rare genetic disease affecting about 1 in every 40,000 infants. It’s a type of metabolic disorder where there’s a lack of a certain enzyme in the body. That enzyme breaks down a sugar compound called glycogen. The disease occurs because of a mutation in a gene that makes the enzyme. “As the glycogen accumulates, the cells get damaged beyond repair, causing the heart to enlarge, and the child may die within two years of life without treatment,” says Ramesha Papanna, MD, a UTHealth maternal-fetal medicine specialist and research director at the Fetal Center at Children’s Memorial Hermann Hospital. Prior to UCSF’s new treatment, the only way to treat conditions like Pompe disease was through enzyme replacement therapy given to the newborn. At that point, most infants already showed signs of damage, says Katherine S. Kohari, MD, a maternal-fetal medicine doctor with Yale Medicine and assistant professor at the Yale School of Medicine. “By giving the replacement enzyme before damage sets in, some complications can be prevented, or their onset delayed,” Dr. Kohari explains. “The use of a direct treatment with enzyme replacement is novel and very exciting,” she added. Receiving enzyme replacement therapy in utero is a delicate task. Treatment is usually done by a maternal-fetal specialist, says Dr. Kohari. “Under ultrasound guidance, a needle is placed into the umbilical vein and medication can be infused,” she describes.
Promise for Families With Genetic Disorders
It’s not just Pompe disease that UCSF’s in-utero therapy can treat. “Pompe disease is just one of a group of glycogen storage diseases, and most cause severe disease and often progress to death of the child at very young ages,” says Alan Fishman, MD, a specialty medical officer for maternal-fetal medicine at Pediatrix Medical Group. Dr. Fishman says theoretically, any glycogen storage disease could be treated in the same ways as in Ayla’s case. “The challenge is to characterize the individuals who are at risk and to correctly identify those likely to be severely affected at a young age,” he explains. “In this particular family, this was clear from the family history.” The treatment protocol has already shown promise with other children. According to UCSF, two other patients with lysosomal diseases are currently enrolled in their clinical trial. At the end of October, one of these infants, a baby with Hunter Syndrome, was born at UCSF Benioff Children’s Hospital San Francisco. This baby received fetal therapy while in utero and is currently healthy and well. “At first, I was nervous; I don’t like doctors or hospitals. But Dr. MacKenzie is great,” Mya Queen, the infant’s mom, told UCSF. “The people at UCSF – it’s like a family.”
