What motivates you in your work?
Dr. Bennett: There are actually a number of things that motivate me. I trained as a neuroscientist prior to completing my medical training and I have an enduring interest in understanding how this amazing organ works. A major theme of modern neuroscience is the observation that the nervous system is not a static organ but shows amazing plasticity in the light of experience and of course following injury. I want to understand how such plasticity is mediated.
I am also a practicing neurologist and although we have a much better understanding of how the nervous system responds to injury, this has not yet been translated into neuroprotective therapies. So of course I would like this new knowledge to be turned into new treatments for my patients.
Can you explain the background to your project?
Dr. Bradbury: The nervous system is divided into the central nervous system (CNS) and peripheral nervous system (PNS). The two main organs of the CNS are the brain and spinal cord. The CNS receives information from and sends information to the PNS.
Nerve cells within the CNS and PNS are surrounded by an insulating layer known as the myelin sheath, which is essential for the proper functioning of the nervous system. Schwann cells supply the myelin in the PNS, whereas oligodendrocytes supply the myelin in the CNS.
After spinal cord injury it’s common for nerve cells to lose their myelin sheath, leaving them unable to transmit vital message from the brain to and from the body. Oligodendrocytes try to re-grow and create new myelin but they have very limited success.
However at the same time, a fascinating phenomenon occurs. Schwann cells, which usually only exist in the PNS, can be identified in the spinal cord after injury. Whilst oligodendrocytes struggle to re-myelinate the nerve cells, interestingly these re-located Schwann cells have much greater success.
There are a number of research groups working to understand why and how this Schwann cell phenomenon occurs in the spinal cord after injury. Within this research neuregulin-1 (NRG1), a growth factor expressed on the surface of cells, is a hot topic.
What is the focus of your project work?
Dr. Bennett: NRG1 is a growth factor, which is expressed by axons, which can be seen as the ‘cables’ carrying electrical signals in the nervous system. NRG1 signals to glial cells acting as an instruction so that when these cells contact axons they wrap myelin around the axon so insulating it. Our research group is interested in the role of NRG1 in regulating the development of glial cells but more importantly how this signal may be important after injury to the nervous system in order to promote repair.
We have created a ‘knock-out’ model, which suppresses NRG1 in adulthood and explored its effects. Initial findings have revealed that knocking-out NRG1 results in less remyelination of axons by Schwann cells after spinal injury, with the consequence of impaired locomotion. This implies that NRG1 is playing a critical role in the body’s natural recovery process and the restoration of function in damaged cells.
As well as continuing to explore the effects of ‘switching-off’ NRG1, we are also looking at the possibility of stimulating an increase NRG1 signalling. If NRG1 is playing a key role in endogenous recovery after injury, it is hoped that increasing NRG1 expression will lead to an increase in its healing effects.
We are also interested to know whether it’s just re-myelination which NRG1 regulates. So we are also exploring NRG1’s impact on preventing neurone death and modulating inflammation after an injury has occurred.
What is the ultimate goal of your project?
Dr. Bennett: Ultimately, we want to better understand the role of NRG1. The long-term hope is that an intervention, drug or treatment could be developed which uses this growth factor to save and restore functions affected by spinal cord injury. There’s a lot more work to do before we get to that stage however this ultimate goal is always at the back of our minds.
How do you see the field of spinal cord injury research developing over the future?
Dr. Bradbury: The field of spinal cord injury research is evolving all the time, with exciting new discoveries and new insights into why the spinal cord does not repair itself after injury. With this knowledge we we can then try to target these with new experimental therapies. For example we have identified molecules in scar tissue that stop new nerves from growing and we can break these down with an enzyme therapy. Therapies such as this can lead to nerve regeneration, improved connections, remyelination, and enhanced function in those nerve fibres that were spared by the injury. This is a great step forward and many of these experimental therapies are currently in, or being considered for, clinical trials. The current goal is to bring more of these therapies to the clinic, with the aim of acheiving repair over several spinal segments. This could have immense consequences for spinal injured patients, for example the return of hand function or bladder and bowel function. I believe this will be possible in the not too distant future and that these are exciting times.