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Deadly Disease Is Treatable, But Newborn Screening Patchwork Leaves Many Vulnerable

Deadly Disease Is Treatable, But Newborn Screening Patchwork Leaves Many Vulnerable

(Bloomberg) -- Mateo Medina started having trouble breathing when he was two weeks old, and doctors told his parents he was unlikely to live to his second birthday. Now 8, he is beating the odds, though he has never walked or talked.

His brother, Javier, is 3. He talks nonstop, often about dinosaurs, and walks, but doesn’t run the way kids his age would. When he tries to jump, his feet don’t leave the ground.

Amelia, their 1-year-old sister, says “mama,” “dada,” and “bye-bye.” She shows no sign of the genetic disorder they share: a severe form of spinal muscular atrophy known as SMA type 1. The disease, passed on by chance from a child’s parents, is as devastating as it is rare.

Their mother, Amy Medina, is amazed by her children, and by the progress medicine has made since Mateo was diagnosed.

“It’s a miracle, seeing these kids and what they can do,” said Amy, a 38-year-old social worker. “You read SMA type 1 on the Internet, and it’s a death sentence. Now you see these kids being treated early and they are walking and talking.”

But the Medinas in Fond du Lac, Wisconsin, also embody a cruel reality about the disease: Being born a few years before a drug is developed, with an inexperienced doctor, or in a state that doesn’t screen for the condition, can mean the difference between a healthy life and one of permanent disability. To check the ravages of SMA, treatment has to happen early — often in the first weeks or months  of a child’s life.

When Mateo was born in 2011, there was no treatment. Today, there are two therapies for SMA. Even so, many places still don’t screen for the disease. Confronted with dozens of rare disorders, it’s up to each state to decide which ones to test for. Only seven states currently screen for SMA, with about 20 more working on adding it. Nationwide, a thousand children with otherwise treatable illnesses are missed, catastrophically, each year. 

Mateo’s siblings were, in a certain heartbreaking way, lucky. Before they were born, their brother’s disease served as warning. Javier and Amelia were tested in utero and treated within a couple of weeks of birth. Javier got a powerful injection made by Biogen Inc., Spinraza. Amelia received Spinraza, as well as an experimental gene therapy, Novartis AG’s Zolgensma, that was subsequently approved, in May 2019.

Unable to Move

SMA progressively destroys motor neurons in the child’s brain and spine until they have no voluntary muscle control. Some experts compare it to Lou Gehrig’s disease in adults, like being trapped inside your body, aware but unable to move.

“The data is overwhelming that the earlier we treat, the more successful the treatment is,” said Jerry Mendell, a neurologist at Nationwide Children’s Hospital in Columbus, Ohio, and a pioneer in gene therapy.  “If we treat early enough, I believe we can completely reverse the disease.”

The U.S. Department of Health and Human Services recommends testing newborns for about 60 disorders in its Recommended Uniform Screening Panel, or RUSP. It periodically updates it, and SMA was added in 2018 after the first treatment came to the market. But each state does its own lab testing and sets its panel.

Deadly Disease Is Treatable, But Newborn Screening Patchwork Leaves Many Vulnerable

Missouri was first to adopt SMA screening in July 2017, six months after Spinraza was approved, followed by Minnesota and Utah early the next year. Overall, public health officials estimate 1 in 300 newborns have a condition that like SMA could be detected with screening. 

But only about half of states screen newborns for the disease or are planning to. As a result, some children slip through.

Mary McInturff’s daughter Charlotte seemed healthy when she was born in July 2018 in Winchester, Virginia, where SMA isn’t screened yet. But during a standard checkup, the pediatrician noticed that Charlotte wasn’t moving the way a 2-month-old does. She seemed in a permanent “milk coma,” the sleepy state in infants after nursing. Three weeks and numerous tests later, the family got the diagnosis of spinal muscular atrophy.

Charlotte was treated with Spinraza, then Zolgensma, and has gotten stronger. She's able to sit with help and has said her first word, “mama,” but she still needs a feeding tube and uses a machine to help her breathe when she’s battling a virus or other germs.

“As a mom, you’re angry about why this wasn’t treated earlier,” McInturff said. “If Charlotte had been diagnosed at birth or in utero, her life would be completely different.”

Deadly Disease Is Treatable, But Newborn Screening Patchwork Leaves Many Vulnerable


Deciding what diseases to add to a basic battery of newborn tests, however, isn’t a simple matter of checking off another box on a list.

Each state uses its own calculus, based on factors like how common the genetic disorders are among its population, the availability of treatments and support groups, and cost. Some states require that every disorder on the RUSP be covered, while others don't even test for all 35 conditions in the agency's “core panel.”

There’s no commercial SMA screening test available, so state labs have to build them in-house. It requires a molecular test, which can cost as much as $10 per child, while others like congenital hypothyroidism cost as little as $1, said Linh Hoang, vice president of reproductive health at PerkinElmer, a leader in newborn screening.

While rates may seem low for SMA screening across the country, they are far ahead of many conditions just a few years after a first treatment has been approved, said Wildon Farwell, head of clinical development for Spinraza at Biogen.

SMA is caused by an inherited mutation in the survival motor neuron gene, identified in 1995. A healthy version makes a protein needed for the nerves that control muscles to function. Without it, they wither and waste away, eventually taking the muscles with them. Once they are gone, there's no way to revive them. Both Spinraza and Zolgensma bolster production of the protein.

Of the 4 million babies born each year in the U.S., about 15% are screened for SMA, said David Lennon, president of the Novartis unit that developed Zolgensma. In all, about 400 have the condition, though most aren’t diagnosed until irreversible symptoms appear. Those with less severe forms may seem healthy for years.

Novartis and Biogen know they need to find those patients as early as possible, and have been working with state laboratories to try to expand screening. A lot is at stake, financially. Zolgensma, a one-time treatment that costs $2.1 million, has only been approved for kids under age 2. Biogen’s Spinraza, injected into the spinal column several times a year for life, costs $125,000 per vial.

Even before Mateo Medina was born in July 2011, his mother Amy knew something was wrong. Three of her co-workers were pregnant, and they would compare bellies. Amy could see their babies moving, something she rarely even felt with Mateo. Her doctors waved off her concern. It was soon a pattern.

After Mateo’s birth, his distress was obvious. He didn’t cry or kick. He barely moved as pediatricians crowded into the labor and delivery room. It took an entire month, and a new pediatrician, to get a diagnosis.

“I just heard the death sentence, and I was lost,” Amy said.

A critical benefit of newborn screening is to eliminate that diagnostic odyssey — the agonizing process of trying to figure out what's wrong — said Jaimie Vickery, vice president of advocacy and policy at the advocacy group Cure SMA.

One of the first winners in the screening lottery in Minnesota was Edan Philstrom, though that felt like the furthest thing from the truth to his parents when he was diagnosed in October 2018. The Philstroms had no reason to suspect anything when Edan's pediatrician called five days after his birth.

He was just over 7 pounds, with a dusting of red hair that matched his father’s curls. He had no symptoms, and no family history of the disease. Rory and Carolyn Philstrom had presided over children's funerals as Lutheran pastors, and they braced.

“That’s what I was preparing myself for, like I’m gonna have to watch my child die, and grieve,” Rory said.

Edan has a milder form of the disease, and it’s possible that the family wouldn’t have known for months or years. But Minnesota started screening for SMA seven months before his birth. He was given Spinraza immediately, then received Zolgensma. He started rolling over at 1-month-old and now sits unassisted, an achievement for kids with SMA. He shows no signs of the disease. Thanks to early treatment, it’s possible he never will.

Deadly Disease Is Treatable, But Newborn Screening Patchwork Leaves Many Vulnerable

Over in Wisconsin, where SMA isn’t screened, Javier and Amelia Medina got tested because their brother had the condition. SMA is a rare disease, occurring in about 1 in 10,000 births. But the gene that causes it isn’t so rare. Both parents, Amy and her husband Adan, a stay-at-home dad, are carriers, like about one in every 50 people in the country. Most don’t know it. 

Javier, the middle son, has hit developmental milestone after milestone. He’s started school and is already testing at above his age.

“He surprises us with everything he knows,” Amy said. “We know Mateo is smart, but he can’t talk. Seeing it in Javier is just amazing.”

There are subtle signs of the condition. Javier does need oxygen therapy when he’s not feeling well. Trying to run involves quickly pumping his arms, without a significant change in pace.

The hardest part for him now is getting Spinraza injections every four months, an ordeal that involves 850-mile trips, often by car, to Baltimore, where the trial he enrolled in is still underway. The process involves two days of testing, evaluation and monitoring, and he’s been there a dozen times.

“He knows what is going on and starts crying and doesn’t want to go in,” Amy said. “It’s hard on him. It’s a lot for a 3-year-old to go through.”

The disease has so badly damaged Mateo's muscles that he usually must lay flat, able to sit at a 45-degree angle only for brief periods of time. He also started getting Spinraza, when he was 6, and his parents can see subtle improvements. One side of his mouth will now curve up when he's trying to smile, something they call the Elvis curl. He has regained a small amount of movement in his toes and his feet, and his left index finger and thumb. The biggest benefit has been his breathing, which is noticeably easier.

Only time will tell if Amelia will ever show symptoms or suffer from unknown side effects from gene therapy. For now, she babbles like any toddler does. She's had several colds, but no hospital stays.

“People are amazed that she has SMA,” Amy said.  “You would not be able to tell.”

To contact the editor responsible for this story: Cecile Daurat at cdaurat@bloomberg.net, Drew Armstrong

©2019 Bloomberg L.P.