The study, in which neonatologists from all Dutch academic hospitals participated, was published on Wednesday evening in The Lancet Neurology† Ten babies participated who had suffered a cerebral infarction around birth. This happens to about thirty children in the Netherlands every year. Depending on the location and extent of the damage, the brain damage they sustain causes lifelong motor problems (such as spastic limbs), learning and behavioral problems and epilepsy.
Stem cells can help repair damaged tissue, but the question has long been how to get those stem cells safely into the brain. The route through the blood turned out to be ineffective: the stem cells are then hijacked by large organs such as the lungs and liver. The research group of Cora Nijboer, neuroscientist at UMC Utrecht, discovered an alternative route via the nose in animal research. The stem cells travel up from the nasal cavity in a few hours, attracted by signal substances released by the damaged tissue.
Less damage
This approach has now also been tested in babies for the first time. Ten children with brain damage were given nose drops containing 50 million stem cells from a donor’s bone marrow within a week of being diagnosed. The children were then followed for three months. There were no side effects. And although the study was only designed to demonstrate the safety of the treatment, the researchers were surprised by what they saw on the MRIs, says Manon Benders, professor of neonatology at UMC Utrecht and one of the study leaders.
Compared to the scans made shortly after birth, the motor nerves, which control the movements, were less affected or even restored. The babies also scored better than expected on motor tests. On average, much less damage was visible in the brains of children treated with stem cells than on scans of untreated children.
‘The brains of newborn babies are still developing’, explains Benders. “That makes it possible to repair important connections.”
No side effects
Neuroscientist Vivi Heine, not involved in the study, reacts enthusiastically. ‘The researchers have already convincingly shown in animals that these stem cells contribute to the repair of brain damage, and this is an important next step,’ says Heine, who is researching stem cell technology at Emma Children’s Hospital in Amsterdam. Animal studies have already shown that the stem cells disappear and do not settle in the brain. Now that no side effects have occurred in the babies after three months, it can be assumed that the special nasal drops are safe, says Heine.
The idea is that the stem cells in the brain secrete substances that stimulate the babies’ own brain stem cells to repair. They also dampen the inflammatory response, giving brain cells more room to grow, explains Heine. Professor Benders emphasizes that an official assessment may only be made about the effect of the nasal drops if more children have been followed for a longer period of time. ‘But meanwhile, the first effects are hopeful.’
Her pregnancy had been exemplary, so when Suzanne Nakhla felt less life in her belly after 39 weeks, she wasn’t alarmed. But during a check-up at the hospital, the baby’s heart rate dropped so quickly that an emergency cesarean section was decided.
That night, the newborn Senna stopped breathing three times, later revealed to have had seizures. She had to be rushed to the Sophia children’s hospital in Rotterdam, where an MRI of her brain was made. Father Sebastian Mennes remembers the moment when the doctors entered their room. “We saw right away that they had no good news.” Senna had suffered a major cerebral infarction in the area responsible for motor skills. That would probably leave her with paralysis for life.
There was a chance of recovery, in theory: doctors from the Wilhelmina Children’s Hospital in Utrecht had started an experimental study with stem cells. Within a few days they had to decide whether they wanted to participate. They weighed the risks. It was a study that had just passed the animal testing stage, what if their daughter had a serious side effect? But what was the alternative? Going home and see how she would develop? Wasn’t it also a miracle that this new study came out just now?
And so they took Senna to hospital number three, where the girl, only a few days old, was given nasal drops containing stem cells. The MRI, which was made after three months, brought a wonderful message, says mother Suzanne. ‘There is still some kind of bite out of her brain, but the motor pathways turned out to be well developed.’ Her father calls it ‘pure magic’.
Senna is now one and a half, and during the Zoom meeting with her parents she happily crows through the conversation. Her father says he had taken everything into account: ‘I imagined that she would be excluded from class because she was different and that made me so sad.’ But his daughter seems to be developing into a healthy child. And he was in tears again, but then of happiness, seeing her walk to the table before her first birthday.
How special, they say, that Senna has helped science a little bit. ‘We also wish other parents this good news.’