Neuroscientists regenerate severed spinal cord

Research by scientists at King’s College London may pave the way for new treatments of spinal cord injuries. Spinal cord injuries typically arise from car accidents, violence, falls and sports injuries, with an average of two new cases admitted every day in the UK alone.

In research published in Nature* this week, scientists from the Centre for Neuroscience Research at King’s, show how an enzyme enables severed spinal nerve fibres to repair themselves. This discovery may form part of a treatment for the victims of spinal cord injuries in the future.

One of the reasons why nerves cannot regenerate after a spinal cord injury is because scar tissue forms at the injury site. Cells surrounding damaged nerves (glial cells) multiply to form a dense scar and also secrete barrier molecules that nerves are unable to cross. This stops the nerves from growing back. However, a bacterial enzyme called chondroitinase ABC destroys some of the molecules in the scar, allowing nerves a path to grow back along.

Dr Elizabeth Bradbury, lead author and researcher at King’s College London, said: “The enzyme may become part of a developing arsenal of therapies to treat people suffering from paralysing injuries.”

“After damage to spinal cord tissue, a complex jungle of molecules is deposited in the scarred area. Chondroitinase ABC acts like a ‘molecular machete’, cutting a path through the jungle of molecules that usually prevent spinal cord nerves growing back into these damaged areas.”

“Spinal cord injury is a major neurological problem because damage to the spinal cord is irreversible. The injured nerves fibres do not normally re-grow, so communication with other nerve cells is lost. This may mean paralysis and loss of sensation which can obviously be devastating for patients.”

Rats with spinal injuries were treated with Chondroitinase ABC and in a series of tests it was demonstrated that nerve regeneration occurred in both the sensory and motor nerves in the spinal cord. It was also shown that cells above the damaged area were able to transmit signals and communicate to those below.

Most importantly, the team at King’s College London demonstrated that rats with spinal injuries, after treatment with the enzyme, recovered much of the neurological function they had lost. The rats, which were previously disabled, showed near normal walking behaviour, although they did not recover normal sensory function. This is the first time it has been shown that treatment with chondroitinase ABC can cause recovery of function following a spinal cord injury. Treatments such as this, which target the scar, may eventually be used in combination with therapies that tackle the other problems that prevent nerves from re-growing. Additional therapies include antibodies to neutralise other inhibitory influences, grafted nerve cells to bridge the hole between cord stumps and growth factors to give nerves a regenerative boost.

Dr Bradbury concluded: “This is a great advance, but not some sort of miracle cure. There are still many other blocks that must be overcome before complete spinal cord repair can be achieved in humans. In terms of treating people, we could see clinical trials involving this treatment as part of a multi-targeted therapy starting within the next five years.”

Notes:

* Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature11 April, 2002; Vol 416, p636-640.

Collaborators include researchers from University of Cambridge and Queen Mary, University of London.

The research has been made possible through the generous funding of the Wellcome Trust.