Promising Results of the First Prenatal Treatment for Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is a progressive neurodegenerative disease that begins before birth. Scientists at St. Jude Children’s Research Hospital led the first treatment of SMA in utero with the orally administered drug Risdiplam. More than two years after the child’s birth, no detectable signs of spinal muscular atrophy were observed.

This study demonstrates that prenatal treatment of SMA is feasible and supports further investigation of this approach. The results were published in a letter to the New England Journal of Medicine. “Our primary goals were feasibility, safety, and tolerability, so we are very pleased that both the mother and child are doing well,” said the study’s corresponding author, Richard Finkel, MD, Director of the St. Jude Center for Experimental Neurotherapeutics and a member of the Division of Pediatrics. The results suggest that it would be worthwhile to further explore the application of prenatal interventions in SMA.

Spinal Muscular Atrophy: A Unique Clinical Protocol

Spinal Muscular Atrophy is caused by a deficiency of survival motor neuron protein and occurs in approximately one in 11,000 births in the United States. If untreated, SMA type 1 (SMA-1), the most common and severe form, causes progressive muscle weakness that leads to death. Current treatments for SMA-1 in infants have demonstrated improved survival and motor function, especially when administered soon after birth, before symptoms begin. However, a cure is not possible.

The survival motor neuron protein is needed most during the third trimester of fetal development and the first three months of life after birth. The severity of symptoms is therefore closely related to the timing of intervention. In response to this clinical need, researchers at St. Jude Children’s Research Hospital established a unique clinical protocol to study risdiplam in a single patient as part of the Pediatric Translational Neuroscience Initiative. The goal was to determine the feasibility of treating a fetus with SMA type 1 in utero.

The parents in this case were both known carriers of SMA gene variants and already had a child with SMA type 1 who died at 16 months before current treatment options were available. Genetic testing performed via amniocentesis confirmed that the fetus lacked copies of the survival motor neuron gene, which, combined with the family history and other genetic information, indicated a high likelihood that the child would be born with SMA-1. Risdiplam was administered to the expectant mother in the last six weeks of pregnancy.

Safe and Promising Results Encourage Future Research

Shortly after birth, the infant was diagnosed with three developmental abnormalities: a ventricular septal defect (which resolved), optic nerve hypoplasia, and brainstem asymmetry, resulting in corresponding delays in vision and overall development. These abnormalities probably occurred early in fetal development, before the fetus was treated with Risdiplam. The child is now two and a half years old and continues to be monitored regularly at St. Jude. During the course of the examination, the researchers have not found any real evidence of spinal muscular atrophy. The research results demonstrate the safety and feasibility of the approach and argue in favor of a larger study.