Antibody molecules sprayed into the noses of rats have led to the repair of stroke-like damage in the brain, and it may be because the drugs travelled through nerve cells for smell
16 January 2023
Medicines that combat the effects of a stroke can be delivered to the brain by squirting them up the nose – at least in rats.
Getting large drug molecules into the brain has long been seen as a key medical challenge. Most such compounds can’t reach the brain in large quantities because the walls of the blood vessels that perfuse the brain are highly impermeable, creating what is known as the blood-brain barrier.
Previous studies have suggested that some drugs may be able to reach the brain through the nose by travelling up nerve cells that detect smell, because these have long fibres that stretch from the nasal passages to the brain.
It was unclear, though, if enough of the molecules would travel to the brain to have a medical benefit, says Martin Schwab at the Swiss Federal Institute of Technology in Zurich.
To find out, Schwab and his colleagues tested nasal delivery of antibodies that block a compound in the brain called Nogo-A, which normally inhibits the growth of brain cells.
The team first mimicked the effects of a stroke in rats by stopping blood from flowing to parts of their brains. This meant the animals became clumsier at reaching through a hole for food pellets, something they could do easily beforehand.
In rats that received a nasal spray of antibodies once daily for two weeks, their success at this task improved to about 60 per cent of their former ability by four weeks after their injury. In animals given a placebo treatment, the figure was about 30 per cent.
When Schwab’s team examined the rat brains, they found that the treated rats had sprouted more new nerve fibres. “We have reached a level of antibodies that is effective in repairing a large stroke lesion,” says Schwab. “It shows there’s a natural regenerative power within the brain and you just have to take the brakes off to let it happen.”
Moein Moghimi at Newcastle University, UK, says any way of getting drugs into the brain would have wide benefits. But this study doesn’t prove that the antibodies reached the brain by travelling up the nerves, because they could have been absorbed from the nose into the bloodstream, from where small quantities could have reached the brain, he says.
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