Genetic Disorder Treated In Utero For The First Time

“She’s our little miracle baby and she’s shown us that (the treatment) works,” says Sobia Qureshi, mother of 16-month-old Ayla.
Ayla, who lives in Ottawa with her parents Zahid Bashir and Sobia, underwent the experimental treatment in 2021 while still a fetus after prenatal tests showed she had Pompe disease.
It is an inherited and usually fatal disorder that took the lives of two of her sisters.  Ayla, however, is not only surviving, but thriving, according to her family and doctors, as described in a New England Journal of Medicine study that describes her case as the world’s first intrauterine treatment for the disease.
Doctors at The Ottawa Hospital and the Children’s Hospital of Eastern Ontario have teamed up to provide a missing enzyme to those with Pompe.  The treatment is sometimes used in babies after birth or in adults with the disease.  But in the landmark case, Ayla’s mother received six injections between the 24th and 37th week of pregnancy.  The enzyme was administered into the fetal umbilical cord vein using ultrasound-guided needles.
Babies born with infantile Pompe disease usually have an enlarged heart and muscle weakness.  The disease is rare, occurring in fewer than one in 100,000 babies, although it is more common in certain ethnic backgrounds.  It is caused by a faulty gene that prevents cells from releasing certain waste products, which build up in the body.
“There is damage that is done even before a baby is born, and that damage cannot be reversed,” said Dr.  Pranesh Chakraborty, a pediatrician and metabolic geneticist at CHEO and co-leader of the case study, who treated the family’s previously affected children.  “No matter how well you behave after a baby is born, you may never be able to achieve the optimal outcome,” she told CTV News.
Zahid and Sobia were initially unaware that they both carried the genes for this disease.  They also have two unaffected children, ages 13 and 5.
When they decided to try for another child, they knew it was a genetic roll.  When tests confirmed Sobia was carrying another fetus with Pompe, she was devastated.
“Shock, fear, obviously upset, but then we took a breath and said, ‘OK, how do we proceed now?’
The research of Dr.  Chakraborty on their behalf led him to a team at the University of California, San Francisco (UCSF Health), where Dr.  Tippi Mackenzie and her team were preparing to start a study of 10 children with diseases like Pompe to see if giving them the treatment before birth would normalize their development.
Studies in mice showed that early treatment worked, with the suggestion that the replacement enzyme could better cross the blood-brain barrier, improving the development of the neurological system in utero.
When Dr. Chakraborty approached the Ottawa couple early in the pregnancy in 2021, they were excited but declined.  The infusions would require Sobia to be in California for up to six months.  She and Zahid were worried about traveling during the pandemic and left their other two children in Canada.
Scientists, however, have come to an agreement.  The Ottawa medical team could use the study protocol, with UCSF researchers helping with the process and recording the results.
After six prenatal enzyme replacement treatments at the Ottawa hospital, Ayla was born on June 22, 2021. Tests show her heart and muscle development are normal.
Ayla’s first laugh as an infant was an important sign.
“That’s something our other two daughters couldn’t do,” Zahid said.
Now she’s a busy toddler, walking, climbing and getting into cabinets and cupboards, “which is fantastic,” her parents say with a smile.
Ayla underwent experimental treatment in 2021 while still a fetus after prenatal tests showed she had Pompe disease. 
Doctors also watched for risks to the mother and fetus, including the risk of premature birth.  But there were no problems in Ayla’s treatment.
“So we learned from this family that it is possible to diagnose and treat a fetus with infantile Pompe before birth,” said Dr. Mackenzie.  “I feel it represents a new chapter in fetal medicine, one in which we can potentially treat and potentially cure fetuses with many genetic diseases.”
“I think this could be a game changer for families to know,” said Brad Critden, the executive director of the Canadian Pompeian Association, from his home in Pentiction, BC.  The key is early testing.
“Pompeii is very underdiagnosed,” he said, with some US states now beginning routine screening of newborns.  Pompe is not approved for infants in Canada.
Ayla, meanwhile, continues to receive weekly infusions of enzyme therapy at CHEO to maintain her growth.
US researchers are now recruiting other families with pregnancies where the fetus has been found to have Pompe disease or similar genetic disorders.
Canadian researchers want to treat other patients as part of a study, but have been unable to find funding to continue the work they started with Ayla.
Her parents know she will be closely monitored in the coming years.
“We don’t know what’s going to happen in the future. All I hope is that he has a happy, healthy and full life,” Sobia said.

title: “Genetic Disorder Treated In Utero For The First Time " ShowToc: true date: “2022-12-20” author: “Billie Beech”

“She’s our little miracle baby and she’s shown us that (the treatment) works,” said Sobia Qureshi, mother of 16-month-old Ayla.
Ayla, who lives in Ottawa with her parents Zahid Bashir and Sobia, underwent the experimental treatment in 2021 while still a fetus after prenatal tests showed she had Pompe disease.
It is an inherited and usually fatal disorder that took the lives of two of her sisters.  Ayla, however, is not only surviving, but thriving, according to her family and doctors, as described in a New England Journal of Medicine study that describes her case as the world’s first intrauterine treatment for the disease.
Doctors at the Ottawa Hospital and the Children’s Hospital of Eastern Ontario have teamed up to administer an enzyme that is missing to those with Pompe.  The treatment is sometimes used in babies after birth or in adults with the disease.  But in the landmark case, Ayla’s mother received six injections between the 24th and 37th week of pregnancy.  The enzyme was administered into the fetal umbilical cord vein using ultrasound-guided needles.
Babies born with infantile Pompe disease usually have an enlarged heart and muscle weakness.  The disease is rare, occurring in fewer than one in 100,000 babies, although it is more common in certain ethnic backgrounds.  It is caused by a faulty gene that prevents cells from releasing certain waste products, which build up in the body.
“There is damage that is done even before a baby is born, and that damage cannot be reversed,” said Dr.  Pranesh Chakraborty, a pediatrician and metabolic geneticist at CHEO and co-leader of the case study, who treated the family’s previously affected children.  “No matter how well you behave after a baby is born, you may never be able to achieve the optimal outcome,” she told CTV News.
Zahid and Sobia were initially unaware that they both carried the genes for this disease.  They also have two unaffected children, ages 13 and 5.
When they decided to try for another child, they knew it was a genetic roll.  When tests confirmed Sobia was carrying another fetus with Pompe, she was devastated.
“Shock, fear, obviously upset, but then we took a breath and said, ‘OK, how do we proceed now?’
The research of Dr.  Chakraborty on their behalf led him to a team at the University of California, San Francisco (UCSF Health), where Dr.  Tippi Mackenzie and her team were preparing to start a study of 10 children with diseases like Pompe to see if giving them the treatment before birth would normalize their development.
Studies in mice showed that early treatment worked, with the suggestion that the replacement enzyme could better cross the blood-brain barrier, improving the development of the neurological system in utero.
When Dr. Chakraborty approached the Ottawa couple early in the pregnancy in 2021, they were excited but declined.  The infusions would require Sobia to be in California for up to six months.  She and Zahid were worried about traveling during the pandemic and left their other two children in Canada.
Scientists, however, have come to an agreement.  The Ottawa medical team could use the study protocol, with UCSF researchers helping with the process and recording the results.
After six prenatal enzyme replacement treatments at the Ottawa hospital, Ayla was born on June 22, 2021. Tests show her heart and muscle development are normal.
Ayla’s first laugh as an infant was an important sign.
“That’s something our other two daughters couldn’t do,” Zahid said.
Now she’s a busy toddler, walking, climbing and getting into cabinets and cupboards, “which is fantastic,” her parents say with a smile.
Ayla underwent experimental treatment in 2021 while still a fetus after prenatal tests showed she had Pompe disease. 
Doctors also watched for risks to the mother and fetus, including the risk of premature birth.  But there were no problems in Ayla’s treatment.
“So we learned from this family that it is possible to diagnose and treat a fetus with infantile Pompe before birth,” said Dr. Mackenzie.  “I feel it represents a new chapter in fetal medicine, one in which we can potentially treat and potentially cure fetuses with many genetic diseases.”
“I think this could be a game changer for families to know,” said Brad Critden, the executive director of the Canadian Pompeian Association, from his home in Pentiction, BC.  The key is early testing.
“Pompeii is very underdiagnosed,” he said, with some US states now beginning routine screening of newborns.  Pompe is not approved for infants in Canada.
Ayla, meanwhile, continues to receive weekly infusions of enzyme therapy at CHEO to maintain her growth.
US researchers are now recruiting other families with pregnancies where the fetus has been found to have Pompe disease or similar genetic disorders.
Canadian researchers want to treat other patients as part of a study, but have been unable to find funding to continue the work they started with Ayla.
Her parents know she will be closely monitored in the coming years.
“We don’t know what’s going to happen in the future. All I hope is that he has a happy, healthy and full life,” Sobia said.