HQ Team
February 27, 2025: A study published in The New England Journal of Medicine (NEJM) reveals that administration of the oral drug risdiplam to an infant in the womb for type 1 spinal muscular atrophy (SMA), the most severe form of the rare genetic disorder, has resulted in her survival beyond the expected two years. This is the first time the drug was administered in the womb rather than after birth.
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. Such children do not survive beyond two years of age, but this child is already two and a half years old with no disease symptoms.
Under the program, the pregnant mother was given a dose of risdiplam each day for six weeks before giving birth. The medicine reached the fetus through the umbilical cord blood and the amniotic fluid bathing her fetus. After birth, it was the infant that was given the daily oral drug.
Pediatric neurologist Michelle Farrar, Australia, told Nature that the baby girl with SMA “has been effectively treated, with no manifestations of the condition” even 30 months after birth.
The child has shown no signs of muscle weakness and has normal muscle development. “That’s obviously very reassuring,” says Finkel, who recommends lifelong monitoring of the child.
Although it involves just one individual, the study highlights “how important early treatment is”, says Farrar. “The therapeutic window that we’re targeting is very narrow.”
SMA, is a leading genetic cause of infant mortality. SMA type 1 is a condition marked by rapid motor neuron degeneration, respiratory failure, and typically death by age two without treatment. Infants who received risdiplam orally within the first six weeks of life show remarkable outcomes:
SMA care
Risdiplam, a daily liquid medication, works by modifying the SMN2 gene to boost production of the survival motor neuron (SMN) protein, which is critically deficient in SMA patients. Unlike invasive therapies like Spinraza (intrathecal injections) or the one-time gene therapy Zolgensma (intravenous), risdiplam’s oral route offers accessibility and ease for families.
In 2020, after the FIREFISH trial, risdiplam was approved by the FDA. Earlier interventions, such as pre-symptomatic Zolgensma administration, have shown similar success, underscoring the importance of newborn screening. However, risdiplam’s oral formulation and scalability address key barriers: Zolgensma’s $2.1 million price tag and Spinraza’s lifelong lumbar punctures.
Dr. Claudia A. Chiriboga, a neurologist at Columbia University, stated, “Early treatment is pivotal. Risdiplam’s ability to cross the blood-brain barrier and its ease of use make it a game-changer, particularly in regions with limited healthcare infrastructure.”
Challenges and future directions
Researchers emphasize the need for long-term data to assess sustained efficacy. Meanwhile, global access remains a hurdle; risdiplam costs approximately $340,000 annually, though lower than gene therapy alternatives.
This study reinforces the transformative potential of early risdiplam use in SMA type 1, aligning with global shifts toward newborn screening and prompt treatment.
