World first – rare genetic disorder treated in womb

A child who was treated in utero for spinal muscular atrophy (SMA) is showing no signs of the condition over two years later.

The child was treated as a fetus with risdiplam, an orally administered drug consumed by her mother during the weeks prior to her birth, at St Jude's Children's Research Hospital in Memphis, Tennessee. While some abnormalities were seen, specific evidence of SMA such as muscle weakness and decreased motor function have not been observed. This case, published in a letter to the New England Journal of Medicine, presents the first ever in utero treatment of SMA, and suggests how outcomes for SMA treatment may be improved.

'Our primary objectives were feasibility, safety and tolerability, so we're very pleased to see that the parent and child are doing well' said Dr Richard Finkel, director of the Centre for Experimental Neurotherapeutics at St Jude's who was corresponding author of the study. 'The results suggest it would be worthwhile to continue investigating the use of prenatal intervention for SMA.'

SMA is a neurodegenerative condition, found in around one in 10,000 births, caused by a lack of survival motor neuron protein encoded by genes including SMN1 and SMN2. This protein is most important during the third trimester and the months following birth, and so babies with SMA rarely survive more than two years.

The child was confirmed through amniocentesis to have no copies of SMN1, putting them at high risk of the most severe form of SMA. Additionally, both her parents were carriers of SMA variants, and had a previous child with the condition who died after 16 months.

Risdiplam increases the levels of the survival motor protein by modulating the expression of SMN2. While the drug is currently offered after two months, since SMA manifests before this stage there is a motivation to begin treatment as early as possible. Indeed, a previous clinical trial from 2024 found that children treated before six weeks old could function far better after two years of treatment.

'The therapeutic window that we're targeting is very narrow,' Professor Michelle Farrar, a paediatric oncologist from the University of New South Wales, Sydney, Australia, and who was not involved in the study told Nature.

While the authors recognised that this study presents only a single case, they highlighted that the results 'may support the consideration of prenatal risdiplam treatment for SMA identified in utero.' Additionally, the study suggests that other genetic conditions could be treated before birth in cases where postnatal treatment is less effective.

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The availability of genetic and genomic testing for people and families affected by rare disease will be discussed at the free-to-attend online event Rare Disease Genomic Testing: How Do We Make Access Equitable and Timely?, taking place online on Wednesday 18 June 2025.

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