Researchers regrow damaged nerve fibres

Researchers from Imperial College London and the Hertie Institute, University of Tuebingen, have identified a possible mechanism for regrowing damaged nerve fibres in the central nervous system (CNS). Their discovery suggests it could one day be possible to chemically reprogram and repair damaged nerves after spinal cord injury or brain trauma.

The researchers were interested in understanding how axons in the peripheral nervous system (PNS) make a vigorous effort to grow back when they are damaged, whereas CNS axons mount little or no effort, often leaving those who suffer spinal cord injury, stroke or brain trauma with serious impairments like loss of sensation and permanent paralysis. If damage occurs in the PNS, which controls areas outside of the brain and spinal cord, about 30% of the nerves grow back and there is often recovery of movement and function.

The researchers looked at mouse models and cells in culture, comparing the responses to PNS and CNS damage in a type of neuron called a dorsal root ganglion, which connects to both the CNS and the PNS. They found that epigenetic mechanisms were at the core of this capacity to regenerate - processes that activate or deactivate genes in response to the environment.

When nerves are damaged in the PNS, they send signals back to the cell body to switch on an epigenetic program to initiate nerve growth. Very little was previously known about the mechanism which allows this ‘switching on’ to occur, but the researchers identified the sequence of chemical events that lead to the ‘switching on’ of the program to initiate nerve regrowth and pinpointed the protein P300/CBP-associated factor (PCAF) as being central to the process.

Wanting to explore whether it was possible to generate a similar response in the CNS, the researchers injected PCAF into mice with CNS damage. This significantly increased the number of nerve fibres that grew back, indicating that it may be possible to chemically control the regeneration of nerves in the CNS. Their results have been published in the journal Nature Communications.

PCAF-driven regenerating axons in injured spinal cord.

“The results suggest that we may be able to target specific chemical changes to enhance the growth of nerves after injury to the central nervous system,” said lead author Professor Simone Di Giovanni, from Imperial College London’s Department of Medicine. “The ultimate goal could be to develop a pharmaceutical method to trigger the nerves to grow and repair and to see some level of recovery in patients.

“The next step is to see whether we can bring about some form of recovery of movement and function in mice after we have stimulated nerve growth through the mechanism we have identified. If this is successful, then there could be a move towards developing a drug and running clinical trials with people. We hope that our new work could one day help people to recover feeling and movement, but there are many hurdles to overcome first.”

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