Scar block encourages nerves in spine to regenerate.
Damaged spinal cords in mice have been encouraged to grow back by blocking a scar-causing molecule. The result suggests a fresh approach to treatments for sufferers of spinal cord injury.
Spinal cord injuries have long been considered incurable because the affected nerve cells do not grow back. Depending on the site and severity of damage, patients can be left paralysed and unable to control important bodily functions.
But in recent years, scientists seeking to reverse spinal cord damage have been pursuing a number of different approaches. These include transplanting cells to stimulate growth, removing factors that inhibit repair and using biocompatible materials to ‘bridge’ gaps between damaged nerve ends.
One major barrier to nerve regrowth is scar tissue. Now researchers from the University of Melbourne seem to have found a way to prevent this scarring, which they publish in this week’s Journal of Neuroscience1.
The team found that mice bred without a molecule called EphA4 produce very little scar tissue around damaged Spinal nerves. The researchers believe this is because EphA4 plays an important role in activating cells known as astrocytes, which are responsible for scar-tissue formation.
To test whether reducing scarring helps the animals to heal, the researchers cut the spinal cords of two groups of mice: one group had normal levels of EphA4, the other group lacked the molecule. The injury paralysed the left hind limb of the animals.
The mice that lacked EphA4 regained all of their stride length within three weeks,
and after one month they had recovered ankle and toe movement. In contrast, the control group recovered only 70% of their stride length, and no ankle or toe movement.
The researchers also found that a large percentage of the spinal cord nerves had regrown across the damaged section in the mice that lacked EphA4, compared with hardly any in the control group.
Surprising the experts
Preliminary observations made by the researchers suggest that the same effect occurs in monkeys as well as mice. If it holds true in humans too, then development of drugs that block EphA4 could remove an important obstacle to spinal cord repair.
“This is a very surprising finding,” comments Ole Kiehn, a neuroscientist at the Karolinska Institute in Stockholm, Sweden. He says the result is promising from the point of view of developing treatments. “It needs to be seen, however, that this works in humans,” he cautions.
The complexity of the body’s nervous system means that many factors come into play during spinal cord repair. An effective clinical treatment will almost certainly need to combine a number of different approaches, including surgery.
“I find it very difficult to imagine that one molecule could make the difference between spinal nerves being repaired or not,” says Geoff Raisman, director of the new spinal repair unit at University College London and pioneer of a method that involves transplanting ‘pathway repairing’ cells from the nasal cavity to grow back spinal cord nerves. “I am surprised that they have got these results.”
He notes that the leap from mouse to man is also a large step in the world of spinal cord research. Small animals sometimes get better on their own in a way that humans do not, he points out, regardless of experimental treatment.