Risdiplam: First In-Utero Treatment for Spinal Muscular Atrophy

Researchers have developed a prenatal SMA treatment using risdiplam, an oral drug, with no signs of SMA observed in the child after two years of birth.

Scientists at St. Jude Children’s Research Hospital have developed the first in-uterotreatment for spinal muscular atrophy (SMA). The oral drug risdiplam is administered to the mother during her pregnancy ().

SMA is a neurodegenerative genetic disorder that affects the muscle strength and movement of a baby before birth. The study found that the child did not show any identifiable features of SMA even after two years of birth. The study highlights the feasibility of treating SMA prenatally and supports further research. The findings were published today in a letter to the New England Journal of Medicine.

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‘ Did you know?
Spinal muscular atrophy (SMA), a #geneticdisorder caused by a lack of survival motor neuron protein, affects about 1 in every 11,000 births in the United States. #pregnancy #medindia ’

First Prenatal SMA Treatment

“Our primary objectives were feasibility, safety, and tolerability, so we’re very pleased to see that the parent and child are doing well,” said the study’s corresponding author Richard Finkel, MD, St. Jude Center for Experimental Neurotherapeutics director and Department of Pediatric Medicine member. “The results suggest it would be worthwhile to continue investigating the use of prenatal intervention for SMA.”

SMA is caused by a lack of survival motor neuron protein and occurs in around 1 in every 11,000 births in the United States. If not treated, SMA type 1 (SMA-1), the most common and severe form, results in progressive muscle weakness that leads to death. Currently, treatments for SMA-1 have demonstrated improved survival and motor function in infants, especially if administered shortly after birth before symptoms begin, but is not a cure.

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Early SMA Treatment in the Womb

Survival motor neuron protein is most needed in the third trimester of fetal development and the first three months of life after birth. Symptom severity is, therefore, closely linked with the intervention time point. Due to this clinical need, the St. Jude researchers, as part of the Pediatric Translational Neuroscience Initiative, launched a unique clinical protocol to study risdiplam in a single patient. The goal was to determine the feasibility of starting treatment for a fetus with SMA-1 in-utero.

The parents in this case were both known carriers of SMA genetic variants and had a prior infant born with SMA-1 before current treatments became available, who died at 16 months of age. Genetic testing conducted by amniocentesis confirmed the fetus had no copies of the survival motor neuron gene, which, combined with the family history and other genetic information, was highly predictive of the infant being born with SMA-1. Risdiplam was administered to the expectant mother during the final six weeks of pregnancy.

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Child Born SMA-Free After Prenatal Treatment

Shortly after birth, the infant was diagnosed with three developmental abnormalities: ventricular septal defect (which resolved), optic nerve hypoplasia, and a brainstem asymmetry, with related delays in vision and overall development. These abnormalities are considered to have occurred early in fetal development before exposure to risdiplam.

Now two-and-a-half years old, the child continues to be monitored periodically at St. Jude. “During the assessment, we have seen no signs of SMA,” Finkel said. The research demonstrates the safety and feasibility of the approach and bolsters the case for a more comprehensive study.

Reference:

Risdiplam for Prenatal Therapy of Spinal Muscular Atrophy - (https://www.nejm.org/doi/10.1056/NEJMc2300802)

Source-Eurekalert

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