'The Disease Took Zara, Then Sara. Could Ayla Be Saved?' diff viewer (1/2)

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The Disease Took Zara, Then Sara. Could Ayla Be Saved?	The Disease Took Zara, Then Sara. Could Ayla Be Saved?
2022-11-10 03:36:25 UTC	2022-11-10 14:26:17 UTC (about 11 hours later)
For the first time, doctors have successfully treated a fetus by infusing a crucial enzyme into its minuscule umbilical cord, halting an otherwise fatal inherited disorder known as severe infantile Pompe disease.	For the first time, doctors have successfully treated a fetus by infusing a crucial enzyme into its minuscule umbilical cord, halting an otherwise fatal inherited disorder known as severe infantile Pompe disease.
The baby, Ayla Bashir, now 16 months old, is developing normally, giggling and babbling and toddling in her home in Ottawa.	The baby, Ayla Bashir, now 16 months old, is developing normally, giggling and babbling and toddling in her home in Ottawa.
Behind the result of Ayla’s treatment, published Wednesday in the New England Journal of Medicine, is a medical drama featuring passionate researchers at three medical centers and the doctors who were moved by the family’s plight.	Behind the result of Ayla’s treatment, published Wednesday in the New England Journal of Medicine, is a medical drama featuring passionate researchers at three medical centers and the doctors who were moved by the family’s plight.
The hope — and expectation — is that their experience may pave the way for fetal treatments that alter the course of a variety of severe genetic diseases, including hemophilia and spinal muscular atrophy, and obviate the need for lifelong medical care.	The hope — and expectation — is that their experience may pave the way for fetal treatments that alter the course of a variety of severe genetic diseases, including hemophilia and spinal muscular atrophy, and obviate the need for lifelong medical care.
In keeping with the goal, the group reported that since they submitted their results for publication, a fetus was treated with enzymes for another disease, Hunter’s syndrome, before birth. He was born on Oct. 27, and doctors have continued monitoring his condition.	In keeping with the goal, the group reported that since they submitted their results for publication, a fetus was treated with enzymes for another disease, Hunter’s syndrome, before birth. He was born on Oct. 27, and doctors have continued monitoring his condition.
Ayla — the doctors’ first success — has severe infantile Pompe, a genetic disorder that can be fatal in the first year of life. She is her parents’ fifth child but only the third to survive. The other two, Zara and Sara, died of the disease, and their parents, Sobia Qureshi and Zahid Bashir, watched as it progressively weakened their babies’ muscles, robbing them of their ability to move until, unable to swallow, unable to breathe and with heart muscle so thickened that their hearts were unable to pump, they died.	Ayla — the doctors’ first success — has severe infantile Pompe, a genetic disorder that can be fatal in the first year of life. She is her parents’ fifth child but only the third to survive. The other two, Zara and Sara, died of the disease, and their parents, Sobia Qureshi and Zahid Bashir, watched as it progressively weakened their babies’ muscles, robbing them of their ability to move until, unable to swallow, unable to breathe and with heart muscle so thickened that their hearts were unable to pump, they died.
The idea for the treatment that saved Ayla began with Dr. Tippi MacKenzie, a pediatric surgeon at the University of California, San Francisco. She and her team had previously treated fetuses with thalassemia, a genetic disease caused by lack of hemoglobin. Those fetuses received blood transfusions and a stem cell transplant by inserting a needle into their umbilical cords and supplying fresh blood.	The idea for the treatment that saved Ayla began with Dr. Tippi MacKenzie, a pediatric surgeon at the University of California, San Francisco. She and her team had previously treated fetuses with thalassemia, a genetic disease caused by lack of hemoglobin. Those fetuses received blood transfusions and a stem cell transplant by inserting a needle into their umbilical cords and supplying fresh blood.
That gave her an idea. There are rare genetic conditions known as lysosomal storage diseases, in which a missing enzyme leads to an accumulation of toxic substances in cells. A few of these diseases — including severe infantile Pompe — can be treated by infusing the missing enzyme starting immediately after birth. But as irreversible damage can start before birth, Dr. MacKenzie wondered if she could treat fetuses with these diseases by infusing enzymes through the umbilical cord into their bloodstream.	That gave her an idea. There are rare genetic conditions known as lysosomal storage diseases, in which a missing enzyme leads to an accumulation of toxic substances in cells. A few of these diseases — including severe infantile Pompe — can be treated by infusing the missing enzyme starting immediately after birth. But as irreversible damage can start before birth, Dr. MacKenzie wondered if she could treat fetuses with these diseases by infusing enzymes through the umbilical cord into their bloodstream.
She tried it with mice that had one of the diseases known as Mucopolysaccharidosis type VII, or MPS7. In its most severe form, it results in a condition known as hydrops fetalis, characterized by a fatal accumulation of fluid in the body.	She tried it with mice that had one of the diseases known as Mucopolysaccharidosis type VII, or MPS7. In its most severe form, it results in a condition known as hydrops fetalis, characterized by a fatal accumulation of fluid in the body.
“The mice did really, really well,” she said.	“The mice did really, really well,” she said.
Then, in 2019, a woman whose unborn baby had severe MPS7 was referred to Dr. MacKenzie. The Food and Drug Administration gave Dr. MacKenzie permission to try infusing the enzyme before birth; unfortunately, by the time the procedure was approved, the disease was so far advanced that Dr. MacKenzie decided not to do it. The baby was stillborn.	Then, in 2019, a woman whose unborn baby had severe MPS7 was referred to Dr. MacKenzie. The Food and Drug Administration gave Dr. MacKenzie permission to try infusing the enzyme before birth; unfortunately, by the time the procedure was approved, the disease was so far advanced that Dr. MacKenzie decided not to do it. The baby was stillborn.
The F.D.A. then suggested Dr. MacKenzie propose a clinical trial that would include any fetuses with severe lysosomal storage diseases with an approved enzyme replacement. The handful of diseases in question are very rare. Just six or seven babies a year in the United States are born with severe infantile Pompe disease.	The F.D.A. then suggested Dr. MacKenzie propose a clinical trial that would include any fetuses with severe lysosomal storage diseases with an approved enzyme replacement. The handful of diseases in question are very rare. Just six or seven babies a year in the United States are born with severe infantile Pompe disease.
Once Dr. MacKenzie got F.D.A. approval in 2020, she waited for referrals of pregnant women whose fetuses had lysosomal storage diseases.	Once Dr. MacKenzie got F.D.A. approval in 2020, she waited for referrals of pregnant women whose fetuses had lysosomal storage diseases.
Ms. Qureshi was the first.	Ms. Qureshi was the first.
She and Mr. Bashir had always wanted children — at least 3. When they married in 2008, they assumed they would have a growing family. Ms. Qureshi, 37, is from Pakistan and Mr. Bashir, ~~41,is~~ from Canada. Their families knew each other. Theirs was an arranged marriage with a simple traditional ceremony in Pakistan, the couple said.	She and Mr. Bashir had always wanted children — at least 3. When they married in 2008, they assumed they would have a growing family. Ms. Qureshi, 37, is from Pakistan and Mr. Bashir, 41, is from Canada. Their families knew each other. Theirs was an arranged marriage with a simple traditional ceremony in Pakistan, the couple said.
When Ms. Qureshi became pregnant in 2010, they had no idea what was to come.	When Ms. Qureshi became pregnant in 2010, they had no idea what was to come.
The couple’s first baby with severe Pompe disease, Zara, was born in 2011. When she was 5 months old, Ms. Qureshi and Mr. Bashir were referred to Dr. Pranesh Chakraborty, a pediatrician at the Children’s Hospital of Eastern Ontario and a specialist in inherited metabolic disorders.	The couple’s first baby with severe Pompe disease, Zara, was born in 2011. When she was 5 months old, Ms. Qureshi and Mr. Bashir were referred to Dr. Pranesh Chakraborty, a pediatrician at the Children’s Hospital of Eastern Ontario and a specialist in inherited metabolic disorders.
The enzyme treatment involved infusing babies with the missing enzyme — acid alpha-glucosidase — every two weeks along with drugs to suppress their immune systems so they did not develop antibodies that would destroy the enzyme.	The enzyme treatment involved infusing babies with the missing enzyme — acid alpha-glucosidase — every two weeks along with drugs to suppress their immune systems so they did not develop antibodies that would destroy the enzyme.
Dr. Chakraborty wanted to start treating Zara, but the day she was supposed to get her first infusion, her lungs collapsed, and she spent a month in intensive care, including 10 days on a ventilator. During that time, she lost all movement in her legs, and her ability to swallow deteriorated so much that she needed a feeding tube to eat.	Dr. Chakraborty wanted to start treating Zara, but the day she was supposed to get her first infusion, her lungs collapsed, and she spent a month in intensive care, including 10 days on a ventilator. During that time, she lost all movement in her legs, and her ability to swallow deteriorated so much that she needed a feeding tube to eat.
She started the enzyme treatment when she was 6½ months old, but her disease progressed.	She started the enzyme treatment when she was 6½ months old, but her disease progressed.
When Zara was 2 years old, her parents made the difficult decision to stop treatment and provide only palliative care. She died peacefully at home, five months later.	When Zara was 2 years old, her parents made the difficult decision to stop treatment and provide only palliative care. She died peacefully at home, five months later.
Dr. Chakraborty, whose own daughter was born four days after Zara, could not help noticing the heartbreaking contrast.	Dr. Chakraborty, whose own daughter was born four days after Zara, could not help noticing the heartbreaking contrast.
In 2016, Ms. Qureshi was pregnant again. Prenatal testing revealed severe Pompe once again.	In 2016, Ms. Qureshi was pregnant again. Prenatal testing revealed severe Pompe once again.
Mr. Bashir and Ms. Qureshi decided to forgo enzyme therapy for their baby Sara and to provide only palliative treatment.	Mr. Bashir and Ms. Qureshi decided to forgo enzyme therapy for their baby Sara and to provide only palliative treatment.
“It was a very, very tough decision,” Ms. Qureshi said. “But there was no hope out there, and we did not want her to suffer.”	“It was a very, very tough decision,” Ms. Qureshi said. “But there was no hope out there, and we did not want her to suffer.”
Sara died when she was 8 months old.	Sara died when she was 8 months old.
In early February 2020, Dr. Chakraborty got a call from Ms. Qureshi. She was pregnant again, and a prenatal test indicated that that fetus, too, had severe Pompe disease.	In early February 2020, Dr. Chakraborty got a call from Ms. Qureshi. She was pregnant again, and a prenatal test indicated that that fetus, too, had severe Pompe disease.
Ms. Qureshi and Mr. Bashir had decided that they wanted to treat this fetus, hoping treatment had improved and that even if after childbirth the baby could not be saved, perhaps her suffering would be less.	Ms. Qureshi and Mr. Bashir had decided that they wanted to treat this fetus, hoping treatment had improved and that even if after childbirth the baby could not be saved, perhaps her suffering would be less.
That evening, Dr. Chakraborty called a researcher at Duke University, Dr. Priya Kishnani, who had developed the enzyme replacement and immunosuppression treatment, asking for advice on how to proceed.	That evening, Dr. Chakraborty called a researcher at Duke University, Dr. Priya Kishnani, who had developed the enzyme replacement and immunosuppression treatment, asking for advice on how to proceed.
“What I wanted to do was to organize the options,” Dr. Chakraborty said. “What’s new? What can we do?”	“What I wanted to do was to organize the options,” Dr. Chakraborty said. “What’s new? What can we do?”
Dr. Kishnani had made finding a way to treat lysosomal storage diseases her mission in 1991, when she was still a medical trainee. There are milder forms of the diseases, in which patients can have no symptoms for years or even decades before their hearts and muscles eventually weaken and they develop serious health problems that require ongoing enzyme infusions. But in the cases Dr. Kishnani saw, the outcomes were tragic.	Dr. Kishnani had made finding a way to treat lysosomal storage diseases her mission in 1991, when she was still a medical trainee. There are milder forms of the diseases, in which patients can have no symptoms for years or even decades before their hearts and muscles eventually weaken and they develop serious health problems that require ongoing enzyme infusions. But in the cases Dr. Kishnani saw, the outcomes were tragic.
“At that time, we used to see babies with infantile Pompe,” she said. “The only information we could give the parents was, ‘This is a lethal disease. Go home and enjoy your baby.’”	“At that time, we used to see babies with infantile Pompe,” she said. “The only information we could give the parents was, ‘This is a lethal disease. Go home and enjoy your baby.’”
The tipping point for her came when her colleagues at Duke attended a funeral for a baby with the disease. She made a vow: This could not continue.	The tipping point for her came when her colleagues at Duke attended a funeral for a baby with the disease. She made a vow: This could not continue.
She and her colleagues embarked on a bid to find a treatment and, a decade later, they were ready to try treating babies after they were born by injecting the missing enzyme.	She and her colleagues embarked on a bid to find a treatment and, a decade later, they were ready to try treating babies after they were born by injecting the missing enzyme.
But when they first tried the treatment, two of the three babies did not survive. The reason, the researchers discovered, was that children had a severe form of the disease — their bodies made none of the enzyme. And when they injected the enzyme, the babies’ immune systems saw it as foreign and made antibodies that destroyed it.	But when they first tried the treatment, two of the three babies did not survive. The reason, the researchers discovered, was that children had a severe form of the disease — their bodies made none of the enzyme. And when they injected the enzyme, the babies’ immune systems saw it as foreign and made antibodies that destroyed it.
Perhaps if they suppressed the babies’ immune systems, the enzymes would be able to work.	Perhaps if they suppressed the babies’ immune systems, the enzymes would be able to work.
She began a study at Duke that enrolled babies from around the world, giving them a five-week course of immunosuppression and regular enzyme infusions.	She began a study at Duke that enrolled babies from around the world, giving them a five-week course of immunosuppression and regular enzyme infusions.
“It works,” she said triumphantly. After treating about 70 babies, she could say with confidence that she found a way to help. The children are still alive — the oldest is about 12 — but often have muscle weakness.	“It works,” she said triumphantly. After treating about 70 babies, she could say with confidence that she found a way to help. The children are still alive — the oldest is about 12 — but often have muscle weakness.