Doctors in the US have treated a fetus with a rapidly progressive congenital disease from inside the womb for the very first time.
Instead of giving medicine to a child with severe neuromuscular complications after they are born, a new case study details how a prospective mother agreed to take the medicine for her developing fetus while she was still pregnant.
A prenatal test had shown that her fetus held two genetic mutations indicating type 1 spinal muscular atrophy (SMA), which usually results in severe muscle weakness and breathing difficulties within six months of birth.
Historically, most children with this type 1 SMA die by their second birthday, usually from respiratory failure. However, the child in this study has so far made it to the age of two and a half years with no sign of symptoms.
The parents of the treated child had previously experienced the loss of their baby to spinal muscular atrophy, and when testing showed their most recent fetus also had the progressive neuromuscular disease, they wanted to know if they could start treatments earlier.
For this single case, the FDA approved the early administration of the oral drug risdiplam, brand name Evrysdi, owned by the pharmaceutical company F. Hoffmann-La Roche AG.
Over the years, randomized controlled trials have shown risdiplam to be both safe and effective at treating spinal muscular atrophy in newborns, and the younger the kids are when they start receiving the medicine, the better the outcomes overall.
In the new study, the pregnant mother took a dose of risdiplam each day for six weeks before giving birth. Testing found that the medicine trickled right through her umbilical cord blood and the amniotic fluid bathing her fetus. After birth, it was the infant that was given the daily oral drug, not the mother.
Pediatric neurologist Michelle Farrar, who is working on a minimally invasive gene therapy treatment for SMA in Australia, told Smriti Mallapaty at Nature that the baby girl with SMA “has been effectively treated, with no manifestations of the condition” even 30 months after birth.
In 2020, risdiplam was first approved by the US Food and Drug Administration (FDA) for kids with spinal muscular atrophy, but only over the age of two months.
But recent clinical trials funded by Roche have found the majority of children with spinal muscular atrophy treated with risdiplam before six weeks of age could swallow, feed, sit, stand, and walk on their own after two years of treatment. None required permanent ventilation.
Risdiplam works to prevent the degeneration of nerve cells in the brain and body by increasing the concentration of a crucial protein, called survival motor neuron (SMN) protein. Active SMN proteins are lacking in those with genetic mutations that cause spinal muscular atrophy.
“In children with SMA, motor neuron degeneration starts before the onset of symptoms, so time is of the essence if we hope to preserve muscle function,” said pediatric neurologist Laurent Servais in a press release for a Roche clinical trial in 2024.
“It’s heartening to see that through early intervention with Evrysdi these children have achieved important milestones like sitting, standing, and walking that would typically be unattainable without treatment.”
Whether or not the recent case study in the US will inspire and embolden doctors and parents to trial risdiplam at earlier stages of development remains to be seen.
“Results in this single case cannot be generalized but may support the consideration of prenatal risdiplam treatment for SMA identified in utero,” write the authors of the correspondence.
The study was published in The New England Journal of Medicine.
