For the first time, scientists have treated a baby with spinal muscular atrophy (SMA) while still in the womb. The mother took a medicine called risdiplam in the last weeks of pregnancy, and continued treatment after birth. This genetic disease causes severe muscle weakness and can be fatal without treatment. Now over two years old, the baby has no signs of the disease. This study could help develop new treatments before birth, bringing hope to other families.
Spinal muscular atrophy (SMA) is a progressive neurodegenerative disease that begins before birth. It is caused by a deficiency of the survival motor neuron (SMN) protein, which is essential for muscle function.
The most severe form, called spinal muscular atrophy type 1, affects babies from the first months of life, leading to progressive loss of movement and, if left untreated, can be fatal.
Researchers at St. Jude Children's Research Hospital have achieved a first: treating a fetus diagnosed with spinal muscular atrophy type 1 while still in the womb using a drug called risdiplam, which is approved to treat the disease in children and adults.
Risdiplam (Evrysdi®) is a medication approved for the treatment of spinal muscular atrophy. It works as a modulator of pre-mRNA splicing of the SMN2 gene, increasing the production of the SMN (survival motor neuron) protein, essential for the survival and function of motor neurons.
Unlike other therapies for spinal muscular atrophy, such as nusinersen (Spinraza®), which requires injections into the spinal cord, or onasemnogene abeparvovec (Zolgensma®), which is administered as a single gene therapy, risdiplam is an oral medication, facilitating continuous treatment.
It was developed to act on both the central nervous system and peripheral tissues, improving motor function and patient survival. Studies have shown that early use of risdiplam can delay or even prevent the progression of spinal muscular atrophy, especially when started before symptoms appear.
Recently, a groundbreaking case showed that the drug can cross the placenta when administered to a pregnant woman, raising the possibility of prenatal treatment for babies at high risk of developing spinal muscular atrophy.
This pioneering study demonstrated that prenatal intervention is feasible and safe, paving the way for future research in the area.
The case involved a couple who knew they were carriers of the mutation that causes spinal muscular atrophy, as they had already lost a child to the disease before current treatments were available.
During the new pregnancy, genetic testing confirmed that the fetus also had spinal muscular atrophy type 1, with the absence of the SMN1 gene and two copies of the SMN2 gene. Since the SMN protein is most needed in the third trimester of pregnancy and in the first months of life, the scientists decided to test the treatment before birth.
From the 32nd week of pregnancy, the mother began taking risdiplam daily, orally, until delivery, which occurred in the 38th week. Tests showed that the drug crossed the placenta and reached the amniotic fluid and umbilical cord blood, reaching the fetus.
The treatment was continued after birth, with oral administration of risdiplam from the eighth day of life.
Today, at over two and a half years old, the child continues to be monitored by doctors and shows no signs of spinal muscular atrophy. No muscle weakness or impaired reflexes have been detected, and motor function tests, muscle ultrasound and electrophysiological tests show that his neuromuscular development is normal for his age.
Prenatal therapy for spinal muscular atrophy (SMA) with risdiplam shows promise in a groundbreaking study published in The New England Journal of Medicine led by Richard Finkel, MD, director of the St. Jude Center for Experimental Neurotherapeutics and a member of the Department of Pediatric Medicine, pictured.
Despite the success, some congenital anomalies were identified after birth, including a small heart defect (which resolved naturally), hypoplasia of the optic nerves, and brain stem asymmetry, causing delays in vision and overall development.
However, these abnormalities were thought to have occurred before risdiplam treatment was initiated.
The results of this study are encouraging and suggest that treating spinal muscular atrophy during pregnancy may prevent symptoms of the disease and improve patient outcomes. However, this is just one case, and more research will be needed to confirm the efficacy and safety of prenatal treatment in a larger group of patients.
If proven in future studies, intrauterine treatment could revolutionize care for spinal muscular atrophy and possibly other genetic diseases, giving affected babies a real chance at healthy development from birth.
READ MORE:
Risdiplam for Prenatal Therapy of Spinal Muscular Atrophy
Richard S Finkel, Samuel H Hughes, JulieAnn Parker, Matthew Civitello, Alfonso Lavado, Heather C Mefford, Lutz Mueller, Heidemarie Kletzl, and Prenatal SMA Risdiplam Study Group
N Engl J Med. 2025 Feb 19. PMID: 39970420
DOI: 10.1056/NEJMc2300802
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