Nearly three years ago, a fetus diagnosed with spinal muscular atrophy (SMA) was treated in utero with risdiplam, a small-molecule drug that boosts SMN protein levels. Now, at 30 months old, the child shows no signs of SMA, an outcome that would have been unthinkable just years ago (1).  By showing that transplacental drug delivery is feasible, this study offers a glimpse of what might be possible for SMA and other genetic disorders. Could prenatal therapy be the next frontier in genetic medicine?

What is SMA?

SMA is a genetic neuromuscular disorder caused by deletions or mutations in the SMN1 gene, leading to insufficient levels of survival motor neuron (SMN) protein. This deficiency results in progressive loss of motor neurons, causing muscle weakness, atrophy, and, in severe cases, respiratory failure. The severity of SMA varies, with type 1 - the most common and severe form - typically leading to significant disability or death in infancy without treatment (2).

Treatment and Mechanism of Action

The fetus, at risk for severe type 1 SMA (confirmed via amniocentesis), was treated in utero with maternal administration of oral risdiplam (5 mg/day) from 32 weeks 5 days’ gestation until delivery at 38 weeks 6 days. The drug’s transplacental passage was confirmed, with 33% of maternal plasma concentrations detected in amniotic fluid and 69% in umbilical cord blood. Following birth, the infant continued risdiplam treatment and remains to do so at 30 months of age (1).

Risdiplam is an SMN2 splicing modifier that increases full-length SMN protein production by promoting exon 7 inclusion in SMN2 transcripts. Unlike SMN1, which is lost in SMA, SMN2 produces only limited functional protein due to inefficient splicing. By correcting this, risdiplam restores SMN levels systemically, reaching both the central nervous system and peripheral tissues. This broad distribution helps preserve motor neurons, slowing or preventing SMA-related (2).

Risdiplam for Prenatal Therapy of Spinal Muscular Atrophy

In their Correspondence in The New England Journal of Medicine, Finkel et al. describe this milestone case, demonstrating the potential for prenatal treatment of genetic disorders. While one case cannot establish a new standard of care, the successful in utero administration of risdiplam and the absence of symptoms 30 months on suggest a promising path forward (1).

With transplacental drug delivery proving effective, this study gives hope that early intervention could someday transform outcomes for SMA and other genetic conditions. As research progresses, prenatal therapy may redefine how we approach inherited diseases, offering affected children a stronger start at life before they’ve even taken their first breath.