Arabella Smygov rolled onto her side, reached out and grabbed a toy fishing lure dangled before her by her brother Jacob.
This scene between a 7-month-old sister and 2-year-old brother may seem unremarkable. But for the Smygov family, it was a miracle.
The family was at Arabella’s weekly physical therapy session at Seattle Children’s North Clinic in Everett. Arabella was diagnosed at 3 months old with spinal muscular atrophy type 1 (SMA1), a severe and often fatal muscular atrophy disease that makes it difficult for children to lift their heads, swallow and even breathe.
“She’s blossoming,” said Arabella’s mother. Sarah Karabut-Smygov, 23, never thought she would get to speak those words. SMA1 typically kills children by age 2.
But a new gene-therapy treatment that went through trials at Seattle Children’s hospital has so far helped Arabella develop at roughly the same rate as other babies her age. Arabella and another baby being treated by the same Seattle Children’s doctor are the first in Washington state to get the new treatment, which was approved last week by the Food and Drug Administration for children up to 2 years old.
Until recently, doctors and families of SMA1 patients just focused on making the child as comfortable as possible. In 2016, the FDA approved a treatment called Spinraza: a shot that needed to be given in a child’s spine every year. The new gene therapy, called Zolgensma, is administered only once, via an IV.
Arabella even smiled throughout the hour the IV was in her leg, said Dr. Fawn Leigh of Children’s.
SMA is a mutation in a gene producing a protein essential to nerves that control muscles. It affects about one in every 10,000 babies, and it kills more babies than any other genetic mutation.
When Arabella was diagnosed, Leigh laid out options for Karabut-Smygov and her husband, Vitaliy Smygov: Their daughter could have the Spiranza shot or apply for the gene therapy, which was still in the trial phase. They opted for the trial.
The choice was obvious, Karabut-Smygov said. It sounded unbelievable that this relatively noninvasive treatment could give Arabella a life many with SMA1 could never hope to have, she said.
“My husband and I were looking at each other like, ‘That’s some magic potion. That sounds amazing,'” she said. “We were desperate to do anything to help her. As parents, you would give an arm and a leg for a kid.“
The Smygovs and the other family in the trial at Children’s didn’t have to pay for the drug because it was acquired for them as part of the hospital’s research.
The cost is substantial: At about $2.1 million, Zolgensma is believed to be the most expensive one-time treatment ever. The drug’s developer, Novartis, will allow insurers to make payments of $425,000 a year for five years, will offer discounts and reimbursements, and will provide refunds if the treatment doesn’t work.
This is only the second gene therapy ever approved by the FDA.
“It’s definitely been an incredible experience,” said Leigh, who has been at Children’s since August. “I was motivated to get this up because of the essential needs. Time is of the essence with SMA1.”
The younger a patient is dosed with Zolgensma, the better the results, she said. Because of this, Leigh wants to get SMA included on a list of diseases all babies are screened for in Washington.
The drug’s approval will give doctors and researchers more information to assesses the impacts of gene therapy, which comes with some risk, said Dr. David Dichek of UW Medicine, who has been working on gene therapies since 1988.
Gene therapies have been used “almost exclusively” on people dealing with aggressive and fatal diseases such as SMA1, Dichek said. But the practice could help make progress in fighting less dire diseases, such as hemophilia and sickle cell anemia, he said.
The Smygovs noticed a change in their daughter about a month after she received Zolgensma. Karabut-Smygov said her husband came home from work one day and saw Arabella sitting in her swing with her head upright, something she hadn’t been able to do without support.
Now, four months post-treatment, Arabella is doing things that would have been unimaginable not long ago.
She can roll over. She can sit upright. Where before her arms were constantly held close to her body, as in a fetal position, now she can extend her arms like other babies her age and move objects from hand to hand.
Arabella has also started noticing things around her other than her mother.
“She actually is interested in toys,” Karabut-Smygov said as her daughter played. “Before we started physical therapy, she knew mom and that is it.”
At a recent physical therapy session, Arabella was fitted with tiny ankle braces with pink straps.
Though the trial at Children’s is over, there’s still more to learn. It isn’t known exactly how Arabella’s body will respond to the treatment in the long term, Leigh said.
“I’m also being very realistic. We need to monitor these babies and see how they develop over time,” she said. “I want to be able to say that in 10 years, in 20 years, we’ll learn more and be able to treat SMA even better.”