For the first time in the world, a case of SMA has been treated in utero

She was supposed to suffer from spinal muscular atrophy (SMA), a rare genetic disease that causes the death of motor neurons and the degeneration of muscles, and instead, at the age of two and a half, she shows no symptoms. The credit seems to go to a drug that acts on the genes administered to her mother when she was still pregnant. The promising results of this trial - the first and so far unique of its kind - are described in the pages of the New England Journal of Medicine and pave the way for an expansion of the treatment, in the hope of saving other young lives.

What is Spinal Muscular Atrophy?

SMA is a rare genetic disease (about 1 in over 10,000 newborns is affected) caused by a mutation in genes that are essential for the survival of motor neurons (Smn1 and Smn2), i.e. those cells that allow the transmission of movement signals to muscles. The consequence is the progressive weakening and death of muscle fibers. In the most serious form of the disease (SMA-1, which occurs when both copies of Smn1 do not work), life expectancy without treatment is very low, no more than three years.

In recent years, however, much has changed. Three different treatments for SMA have been approved, to be administered as soon as possible after birth, which are modifying the history of the disease, although they do not constitute a cure.

A unique experiment, for now

One of these, Roche's risdiplam, was chosen for the innovative trial conducted by researchers at St. Jude Children's Research Hospital in the USA. This drug works in people with SMA1 by increasing the activity of the SMN2 genes, to compensate for the lack of functionality of the SMN1 genes. Risdiplam is usually given orally to affected children after birth, but, despite early intervention, children still show some symptoms of the disease.

In an attempt to further anticipate the times, therefore, the new study planned to administer the drug to the mother, a woman who had already suffered the loss of her first child due to the same condition. The woman - the researchers explain - took risdiplam for six weeks, starting from the 32nd week of gestation.

The results two and a half years after birth

At birth, tests confirmed the genetic diagnosis of Sma-1 for the baby, but also suggested, by analyzing amniotic fluid and umbilical cord blood, that the drug had reached the fetus in utero. The baby, in fact, did not show symptoms of Sma-1: she had higher levels of the Smn protein and less nerve damage than other newborns with the same condition.

Risdiplam therapy was resumed a week after birth and will have to be taken for life, but for now the baby is doing well, with no evidence of neurodegeneration. "Our main goals were feasibility, safety and tolerability, so we are very pleased to see that both mother and baby are doing well," said Richard Finkel , director of the St. Jude Center for Experimental Neurotherapeutics, who participated in the study. "The results suggest that it would be worth continuing to study the use of prenatal intervention for SMA."