Scientists successfully demonstrate a new way to help nerve regeneration in spinal cord injury

A new way of
triggering nerve regeneration to help repair spinal cord injury and in the
longer-term potentially paralysis has successfully been demonstrated by
University of Bristol scientists. The work is published in PLOSONE on Monday 11 December.

There is
currently no cure for spinal cord injury or treatment to help
nerve regeneration so therapies offering intervention are limited. People
with severe spinal cord injuries can remain paralysed for life and this is
often accompanied by incontinence.

A team led by Drs
Liang-Fong Wong and Nicolas Granger from Bristol’s Faculty of Health Sciences has successfully transplanted genetically
modified cells that secrete a treatment molecule shown to be effective at
removing the scar following spinal cord damage. The scar in the damaged spinal
cord typically limits recovery by blocking nerve regrowth.

Previous work by
the team proved olfactory ensheathing cells – which are taken from the ‘smell
system’ where they regenerate and repair throughout life to maintain sense of smell, could be genetically
modified to secrete a treatment enzyme known as chondroitinase ABC (ChABC).
This treatment enzyme is key in breaking down the glial scar at the injury
point of the spinal cord and helping to promote nerve regrowth.

However, while
previous studies have shown ChABC to be effective at promoting nerve regrowth
when injected in experimental models of spinal cord injury as a drug treatment,
it degrades rapidly at body temperature and repeated administration may be
required to maintain efficacy.

In this study,
researchers combined both treatments to treat rodents with spinal cord
injury with genetically modified olfactory ensheathing cells to express
ChABC. Following transplantation of the cells in rodent models the team were
able to demonstrate the successful secretion of ChABC enzyme and removal
of some of the glial scar. This led to increased nerve sprouting in the spinal
cord, suggestive of successful nerve regeneration following the treatment.

The study
provides an important proof-of-concept that this cell transplant strategy
is a viable method to deliver this key ChABC enzyme in a rodent model of
spinal cord injury and could be potentially used to allow the cells to be more
efficient at repairing the spinal cord.

Dr Liang-Fong
Wong from Bristol Medical School, said:

“While these initial results look promising, in order
to determine the longer-term survival of our genetically modified cells
and assess functional recovery, such as recovery of walking or recovery of
continence, we need to carry out further studies to test these cell transplants
in more chronic injury models.”

Dr Nicolas
Granger from the Bristol Veterinary School added:

“Taking this therapy further, for example by applying it to
companion dogs that are naturally affected by spinal cord injury and remained
paralysed, could help improve recovery of walking in these dogs in the longer
term and pave the way for this approach to be applied to human spinal cord
injuries.”

The work was funded
by grants from the Wellcome
Trust, the Biotechnology
and Biological Sciences Research Council (BBSRC) and from the University’s
Elizabeth Blackwell Institute for health research.

Paper

‘Transplantation
of canine olfactory ensheathing cells producing chondroitinase ABC promotes
chondroitin sulphate proteoglycan digestion and axonal sprouting following
spinal cord injury’ by D Carwardine et al in PLOS ONE.