NEWS

Fetal Therapy In-Utero Offers Promise for Families With Genetic Disorders

Photo of Ayla Bashir, toddler who underwent treatment in utero for a genetic disorder
Ayla Bashir, the toddler who underwent treatment in utero for a genetic disorder.

CHEO Media House

Key Takeaways

  • In-utero fetal therapy is a new, innovative treatment for babies with rare genetic diseases.
  • A treatment protocol from the University of California San Francisco helped a family give birth to a healthy, thriving child. They lost two previous children from Pompe disease.
  • UCSF’s treatment protocols offer hope for families everywhere facing the possibility of serious genetic diseases.

There is nothing more devastating than losing a child. One family has found hope—and a chance at raising a healthy child—after losing two previous children to a rare genetic disease. It's all thanks to an innovative treatment protocol out of the University of California San Francisco (UCSF). Doctors at UCSF developed a therapy that treats fetuses for certain genetic diseases in utero, increasing their chances of survival after birth.

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.

Dr. Tippi MacKenzie, pediatric and fetal Surgeon, UCSF Benioff Children’s Hospitals
Dr. Tippi MacKenzie, pediatric and fetal Surgeon, UCSF Benioff Children’s Hospitals.

Maurice Ramirez for UCSF

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.

Toddler Ayla Bashir and her parents visiting a medical facility
Toddler Ayla Bashir and her parents visiting a medical facility.

CHEO Media House

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.”

What This Means For You

If serious genetic diseases run in your family, or you’ve experienced one yourself, you understand how unbearable it can be to live with the unknowns and potential devastations of these conditions. You may be concerned about having a child of your own. That’s why treatment protocols like the ones coming out of UCSF offer such hope. If you have any questions about this protocol, and how it might be able to help you or someone you love, please reach out to your physician or a maternal-fetal specialist.

8 Sources
Verywell Family uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Cohen JL, Chakraborty P, Fung-Kee-Fung K, et al. In Utero Enzyme-Replacement Therapy for Infantile-Onset Pompe’s Disease. New England Journal of Medicine. 2022. doi:10.1056/NEJMoa2200587

  2. UCSF Fetal Treatment Center. In Utero Enzyme Replacement Therapy.

  3. National Organization for Rare Disorders. Lysosomal Storage Disorders.

  4. U.S. National Library of Medicine. In Utero Enzyme Replacement Therapy for Lysosomal Storage Diseases (IUERT).

  5. Chien YH, Hwu WL, Lee NC. Pompe disease: early diagnosis and early treatment make a differencePediatrics & Neonatology. 2013;54(4):219-227. doi:10.1016/j.pedneo.2013.03.009

  6. National Institute of Neurological Disorders and Stroke. Pompe Disease.

  7. Yale Medicine. Fetal Therapy.

  8. UCSF Fetal Treatment Center. In Utero Enzyme Replacement Therapy.

By Wendy Wisner
Wendy Wisner is a lactation consultant and writer covering maternal/child health, parenting, general health and wellness, and mental health. She has worked with breastfeeding parents for over a decade, and is a mom to two boys.