When the phone call came five days after their daughter’s birth, Erin and Jason Schill had already forgotten that a nurse had come into their hospital room to take their hours-old newborn for a routine blood test.
At 6 pounds, 2 ounces and 18 inches long, little Lennox Joy Schill seemed perfectly healthy when she entered the world in the middle of a January night in Brighton.
But now the pediatrician was on the phone, telling Erin that her brand-new daughter, the couple’s first baby, had a rare genetic disorder that affects about one in 11,000 people.
The drops of blood the nurse had taken from the baby’s heel were sent to a lab at the state health department, where it was determined that Lennox had spinal muscular atrophy, a devastating disease that causes muscles to weaken to the point a person can no longer breathe or eat. Historically, babies born with the most severe variation of the disorder have not lived beyond age 2.
The Schills, in disbelief, cried for a few minutes. Then they dialed the number of a genetic counselor at Children’s Hospital Colorado, as their pediatrician instructed.
What happened next, over the course of just 19 days, is nothing short of a medical marvel.
“That was heartbreaking, to watch them die”
In January 2020, Colorado added spinal muscular atrophy to the list of 39 diseases for which newborns are screened. Advances in medicine — gene therapies that trigger the body to produce essential proteins — mean it’s possible to save the lives of infants who previously were destined to die. And those treatments work best when given right after birth.
The screening program, a joint operation with Wyoming, already has identified 13 newborns with spinal muscular atrophy, or SMA. That’s 11 babies born in Colorado, including Lennox, and two in Wyoming in the past 18 months.
Before the screening program, Children’s Hospital typically would diagnose about one to three babies each year, and only after they started showing symptoms that their muscles were weakening. Just two babies were diagnosed in 2018 and only one in 2017.
Parents brought them to the hospital’s pediatric neurology department to find out why they could not sit up, struggled to swallow or had learned to sit up, but then lost the muscle strength. By then, it was too late. There was no reversing the damage.
When Dr. Julie Parsons, a pediatric neurologist at Children’s, began her career, caring for a baby with spinal muscular atrophy basically meant helping the parents cope with their child’s impending death.
She recalled having three SMA babies in adjoining rooms on the third floor of the old Children’s Hospital in Denver, before the Anschutz Medical Campus opened in Aurora. “We would go in every day to see them and watch them die,” she said. “That was heartbreaking, to try to support them and watch them die. That was a horrible thing.”
Now, she can offer hope.
The advancements in SMA treatment that have occurred during Parsons’ near 30-year career are mind-blowing. Other pediatric neurologists have even delayed retirement because they couldn’t stand to leave the field when they could finally save babies from a disease that had killed so many of their youngest patients.
“It has just been the honor of my lifetime to be involved in this entire process,” said Parsons, who started her career in 1993. “It’s difficult to articulate. To see kids who are sitting, running, walking, riding bicycles. It just blows me away.”
People with spinal muscular atrophy are missing a gene that produces a protein essential to the function of motor neurons. Everyone has a backup gene to produce the same protein, and how many backup copies a patient has determines the severity of their disease.
Since the gene was discovered in 1995, understanding and treatment of SMA has evolved at a rapid pace. “It’s been an incredible series of events and discoveries,” Parsons said.
Researchers figured out which protein was missing from the cells of people with the disease. That led to treatments that bind to a person’s genes or deliver copies of the required gene to a patient’s cells, allowing the body to make the needed protein for functioning motor neurons and muscles.
Two gene-therapy treatments are game-changers for SMA
A drug called Spinraza was approved Dec. 23, 2016, coming like a Christmas gift to pediatric neurologists and families with sick babies. “We suddenly had 90 patients who wanted it the next day,” Parsons said.
The drug costs $125,000 per dose, and a baby needs six doses in their first year, then three doses each year for the rest of their life.
A second drug, Zolgensma, was approved in May 2019. This is a one-time infusion — for $2.125 million. Insurance companies at first resisted paying for the therapies, but now Children’s finance and billing team is able to get the treatments covered, Parsons said.
Last year, the FDA approved the first oral drug, called risdiplam, to treat spinal muscular atrophy. But the daily medicine is approved only for babies who are at least 2 months old.
Researchers from Children’s Hospital, which ran clinical trials of both Spinraza and Zolgensma, began pushing in 2017 for statewide newborn screens to detect spinal muscular atrophy. The drugs were allowing babies with the most severe spinal muscular atrophy to walk. Doctors were in awe. Now that successful treatment existed, the best course of action was to make the diagnosis as early as possible, they told the state public health department.
The situation is urgent — by the time a child with SMA is born, they’ve already lost about 50% of their motor neurons.
“The earlier we treat patients, the better the outcomes are,” Parsons said. “If their muscles have atrophied, even with treatment, we can’t make them walk or completely fix them. We just hope to maintain their strength.”
The Colorado Department of Public Health and Environment held a year’s worth of meetings, gathering testimony from parents, doctors at Children’s and others.
Wyoming was going through a similar process, and in late 2019, the two states agreed that both would screen all of their newborns and send any positive cases to Children’s Hospital Colorado, as Wyoming has no pediatric neurology departments. As of this summer, 38 states now screen newborns for spinal muscular atrophy.
In 2020, when 68,000 babies were born in Colorado, the incidence rate of spinal muscular atrophy was just as predicted — one in 11,300 newborns.
The average time from birth to diagnosis in the state screening program has been just four days.
“The best case of the worst-case scenario”
The Schills met with the Children’s Hospital team within 24 hours of hearing the news that Lennox’s screen had come back positive for SMA.
Another blood test determined that Lennox had the most severe kind of the disease, called Type 1. Those results arrived on a Tuesday. Three days later, Children’s Hospital got approval from Cigna, the Schills’ insurance company. And on the next Tuesday, Feb. 16, 2021, the hospital put tiny intravenous lines into Lennox’s arms and she received her one-time, hopefully life-saving dose of Zolgensma.
She was just 19 days old.
The infusion took about one hour, and Erin and Jason got to hold their baby girl as the drug flowed into her body. They stayed at the hospital 22 more hours to make sure she had no negative reaction.
Lennox is 5 months old now and just as strong as a typical baby that age. She laughs, she shrieks when she’s excited, she sits up by herself for a few seconds at a time, and she rolls and wiggles on the floor until she can reach the toy she’s trying to grab. Her legs are strong enough to stand, when her parents help her balance. She’s making moves to crawl.
“Obviously, we feel very lucky,” Erin Schill said. “Kids with this type of SMA maybe learn to put their hand to their mouth.”
Lennox is doing so well that when she goes to follow-up appointments at Children’s, doctors call other doctors into the room just to marvel at her.
Now, the Schills hardly think about the fact their baby has SMA, after thinking about it every few minutes during the first weeks of Lennox’s life. “You put all these hopes and dreams into this … our first baby. It’s a very conflicting thing to be so in love with this baby and also devastated about knowing what they have.”
As hard as the diagnosis was to absorb, especially in the whirlwind of bringing home a baby for the first time, it was far better to know.
“We got the best case of the worst-case scenario,” Erin said. “This has saved her life.”
Questions remain about future prognosis
The rest of the newborns diagnosed and treated thanks to the newborn screen are doing amazingly well, too, Dr. Parsons said.
In the past, babies with Type 1 SMA would never sit up and never eat on their own. Most would end up with a gastronomy tube, called a G-tube, for nutrition. Some parents made the agonizing choice to let their babies go. They would die from inability to breathe or inability to eat — 95% of the time before they were 2 years old.
Babies with Type 2 spinal muscular atrophy could sit but were never able to stand or walk, and their parents typically knew something was wrong by the time they were toddlers. They didn’t use tables and toys to pull themselves to standing as a healthy toddler would do.
And children with Type 3 could learn to walk, sometimes just briefly but perhaps for years. They would lose their ability to walk as the disease progressed, with most needing a wheelchair. They might live into their 20s or 30s, but possibly longer.
Doctors say that likely won’t be the story for the babies identified through the newborn screen.
All the babies are doing far better than they would otherwise, Parsons said. Babies with the least severe type of spinal muscular atrophy seem like typical, healthy kids, thanks to the genetic treatment. Some babies with the most severe type have signs of weakened muscles, but are doing well, Parsons said.
“Everybody is alive. Nobody has a G-tube,” Parsons said. “They’ve done incredibly well compared to what we expected from natural history.”
The hard part of the new screening process, though, is breaking the news to parents who have no idea what’s coming.
The disease is passed down when each parent contributes a recessive gene. Would-be parents can get screened to see if they are carriers, which is recommended by the American College of Obstetrics and Gynecologists, but most people don’t, especially when no one in their family has the rare genetic disorder.
“It’s really, really hard, when they have a beautiful baby, to tell them they have a lethal disease,” Parsons said. “It takes some time for this information to sink in. Some are just in complete shock and denial.”
Children’s has the process organized down to a science, with a genetic counselor available to parents on speed dial.
After hospitals — or midwives in the case of a home birth — send blood samples to the state health department lab, the state sends a message about any positive test to Children’s and to the family’s pediatrician.
In many cases, the pediatrician speaks to a genetic counselor at Children’s before calling the family. Sometimes the pediatrician asks the genetic counselor to have that conversation, mostly because the disease is so rare that it’s likely the pediatrician has never had a patient with SMA. Within 24 hours, pediatric neurologists at the hospital see the baby and counsel the parents.
The Children’s team speaks with the family again the following day, and usually the day after that, and the day after that.
The goal is to have the baby treated either with a first injection via spinal tap of Spinraza or a Zolgensma infusion by the time the baby is 3 or 4 weeks old.
Despite the success, doctors and families wonder about the future. Questions remain about how long the effects of the gene therapy will last, whether the production of the needed protein will decrease in 15 or 20 years.
Lennox and the rest of the babies are a new cohort, the first to receive treatment within weeks of their births. Doctors will want to study them for their lifetimes.
“No one knows what this looks like long term,” Erin said. “We have a lot of faith.”