The girl is two and a half years old and is currently asymptomatic for a rare genetic disease called spinal muscular atrophy (SMA). The treatment was administered while she was still in the womb of her mother, who took the drug at the end of her pregnancy. The girl is currently still taking the remedy. “The baby has received effective treatment and has not shown any signs of the disease,” says Michelle Farrar, a pediatric neurologist at UNSW Sydney (Australia). The New England Journal of Medicine recently published an article reporting the results.
Spinal muscular atrophy affects the motor neurons that control movement and causes progressive muscle weakness. It occurs in one in 10,000 births and is one of the leading genetic causes of death in young children.
The most severe form of the disease occurs in children who lack both copies of the SMN1 gene and have one or two copies of a neighboring gene, SMN2. The effect is that the body does not produce enough protein to maintain motor neurons in the brain stem and spinal cord. The need for this protein is greatest in the first few months. The drug used was Risdiplam, a small molecule modifying the SMN2 gene to produce more SMN protein.
What is interesting about this case is that it was the little girl’s own parents who suggested the possibility of administering the drug in utero. The FDA approved the study for this particular patient. The mother, who was 32 weeks pregnant, received Risdiplam daily for six weeks; the newborn took the drug after one week and will probably have to take it permanently.
At birth, the umbilical cord blood and amniotic fluid were analyzed, and it was found that the drug was reaching the fetus. The girl had higher levels of SMN protein in her blood and less neurological damage, as well as normal muscle development. This work confirms “the importance of early treatment,” Farrar says. “The therapeutic window we are targeting is very narrow.”
In the case of this family, the parents are carriers of genetic variants of SMA-1. They had a child previously who was born with the disease. Since there was no treatment until then, the baby died at 16 months. Amniocentesis tests were performed on the second daughter, which confirmed that she did not have copies of the survival motor neuron gene. This suggested that she would be born with SMA-1. For this reason, the mother was given the drug Risdiplam in the last six weeks of pregnancy.
When the girl was born, she had three abnormalities: optic nerve hypoplasia, ventricular septal defect (which was resolved) and brain stem asymmetry, as well as delays in vision and general development. These abnormalities must have occurred in the early stages of development and before the drug was administered.
The child is currently being monitored regularly. “Over the course of the evaluation, we really didn’t see any signs of SMA. Our primary goals were viability, safety and tolerability, so we’re very pleased to see that both mother and child are doing well. The results suggest that the use of prenatal intervention for SMA may be worth further investigation,” said Richard Finkel, MD, corresponding author of the study, director of the St. Jude Experimental Neurotherapy Center and a member of the Department of Pediatric Medicine.
These types of in utero treatments highlight that human life begins with the fertilization of the egg and that the 9 months spent in the womb are very important, as they are the time for development and growth in all aspects. The news of the cure of such serious illnesses as the one we have reported shows us that what is truly professional from a biomedical point of view is not the elimination of the patient because his health is poor, but the search for the appropriate remedy that, as we have seen, can be applied from the first moments of our existence.
