A group of drugs being trialled for
cancer could also hold promise as a treatment for spinal cord
injury, a study in mice suggests.
Nutlins, which have been found safe
in early cancer trials, promoted nerve regrowth and caused
functional improvements in a mouse model of spinal cord injury.
If further studies in animals prove
successful, the drugs could be tested in human patients within five
to 10 years.
Spinal cord injuries can affect
patients' ability to feel or move parts of their body below the
injury. Spinal cord nerves have a very limited ability to regrow,
so damage is often permanent, and there are currently no effective
treatments.
The new findings are the
culmination of years of research by a team at Imperial College
London and the University of Tuebingen to understand the mechanisms
that stop damaged nerves from repairing themselves.
They identified a series of
proteins that interact to restrict nerve growth. After treatment
with nutlins, which stop these proteins interacting, they were able
to make nerves regrow, first in mice with injuries to the optic
nerve and then in mice with spinal cord injuries.
Mice treated with a placebo made
only a slight recovery in their movement ability after a spinal
cord injury. Mice treated with nutlins made a much stronger
recovery, achieving higher scores on tests assessing their
movement.
Professor Simone di Giovanni of
Imperial College London said: "Unlike in the limbs, nerves in the
spinal cord don't regenerate after an injury. We're only just
beginning to understand the fundamental reasons for this striking
difference.
"We have identified a mechanism
that controls nerve regeneration, and there are already
experimental drugs that target this pathway, suggesting an
opportunity to translate these findings into the clinic. These
results in mice are very encouraging, but they need to be
replicated in further studies in animals. If the next results show
the treatment is effective, it would provide a good justification
for a clinical trial in patients with spinal cord injury."
The paper, The MDM4/MDM2-p53-IGF1 axis controls axonal regeneration, sprouting
and functional recovery after CNS injury, is published
in Brain.