Sildenafil could reduce the severity of the after-effects of newborns who lacked oxygen during pregnancy or at birth, shows a study led by a doctor at the Montreal Children’s Hospital.
Newborns with neonatal encephalopathy are usually treated with therapeutic hypothermia, the only option used to prevent brain damage in such cases, but approximately one third of newborns who receive it still develop significant neurological sequelae. .
“A baby’s brain is different from an adult’s brain,” explained study author Dr. Pia Wintermark, who is a neonatologist at MCH and a scientist in the Child and Child Health Program. in human development from the Research Institute of the McGill University Health Center.
“It is still developing, even after birth. So our idea was to say: could we use his abilities to develop and perhaps stimulate them to be able to repair him? »
Previous research in rats has shown that sildenafil, a molecule better known by its trade name Viagra, can help the brains of adults who have suffered a stroke heal. Dr. Wintermark and her colleagues therefore wanted to know if the same therapeutic effect would be observed in babies.
Between 2016 and 2019, his team studied 24 babies born at 36 weeks of gestation or more, with moderate to severe neonatal encephalopathy, having been placed under therapeutic hypothermia and presenting brain damage despite treatment.
Eight babies received sildenafil starting on the second or third day of life, twice a day for seven days, for a total of 14 doses. A placebo was administered to three other newborns.
The first phase of the study established that the drug can be administered to newborns safely, since only a slight temporary drop in blood pressure was observed in some of them.
The researchers also took the opportunity to verify, in an exploratory manner, the effectiveness of the molecule. They observed, in five newborns after 30 days of life, a partial healing of their lesions, a reduction in the loss of brain volume and an increase in deep gray matter. No such improvement was seen in the placebo group.
“We may not be able to cure them completely, but if at least we could improve their brain and how it works, that would already be a gain for us and for the parents too,” said Dr. Wintermark. And even with our small group of patients, we saw encouraging effects. »
Nine out of ten patients were seen again at 18 months to carry out their neurodevelopmental assessment. In the group given sildenafil, one in six babies developed cerebral palsy, compared to three in three babies in the placebo group. An overall delay in development and fine motor skills was noted in two out of six children who were given the drug, while all three children in the placebo group suffered from it.
Sildenafil, Dr. Wintermark explained, appears to be able not only to prevent the death of certain brain cells, but also to stimulate their regeneration. The molecule would also fight the inflammation that invades a brain that lacked oxygen at birth and reduce damage.
Sildenafil would also contribute to the myelination which occurs during the first months and years of life, a phenomenon which sees nerve cells specialize, added the researcher.
“So, by many means (sildenafil) will replace certain nerve cells a little, prevent there from being too much damage and make them a little more specialized, and it is by all these means that we think that it “is effective,” said Dr. Wintermark.
New studies will now be carried out on larger cohorts in order to confirm the conclusions of phase 1, to define the optimal dosage of sildenafil and to establish its neuroprotective and neurorestorative potential.
The findings of this study were published by the Journal of Pediatrics.