Spinal Research

Spinal Research is the only charity based in the U.K,
which is dedicated to funding research on
an international scale with the sole aim of
ending the permanence of paralysis caused
by spinal cord injury

The purpose of Spinal Research has always been to fund research into the repair of human spinal cord injuries. This research has been very successful, and has now reached the stage where some techniques for partial repair of spinal cord lesions have been demonstrated in animal models. It is probable that if the same techniques could be used in human spinal cord injury patients they would show an improvement in their condition, although not a complete cure. The first trials of these treatments on paralysed people are therefore now being contemplated.

As Europe's major spinal cord injury charity, Spinal Research sees it as its duty to help provide the infrastructure that will be necessary to make it possible for these experimental techniques to be applied to the treatment of paralysed people.

The Trust has started two new initiatives to make this possible; the Research Network and the Clinical Initiative.

Repair of spinal cord injuries will require a combination of several different treatments, and so the Trust has moved quickly to set up the Research Network to deal with this difficult task. All the laboratories funded by Spinal Research are part of this network, which holds regular meetings to co-ordinate the many strands of spinal injury research.

From within this network is drawn a group whose primary responsibility is to turn successful basic research into treatments for spinal injury victims. Taking basic research into the clinic is a major step, and Spinal Research will help this group to achieve it by encouraging research teams within the group to work closely together.

The Clinical Initiative is funding research into ways of assessing the improvements in human patients when the first spinal cord repairs are made. This is a crucial step, because the trials of treatments cannot be started until it is possible to make a proper assessment of the effects on the patients' disability. The Trust is already funding clinical research work in spinal injury units in the UK.

Spinal Research is determined that patients with spinal cord injuries will receive treatments as soon as possible. These two initiatives will ensure that there is no delay in translating the successful basic research programme into effective treatments.

The Trust's Research Network is playing a crucial role in speeding up the process of moving from research into development. It is only possible to fund innovative projects like these because of the generous donations we receive from our supporters. This is why it is so important to support our research in whatever way you can.

Diana, Princess of Wales, supported the trust for many years. Finding successful treatments was an important issue to her. As Royal Patron for the Trust the Princess met many paralysed people and was quick to grasp how devastating spinal cord injury is. Her contribution to the quest of ending the permanence of paralysis was great and will always be remembered. Spinal Research is about creating a better future; a future where spinal cord injury paralysis is a thing of the past; a future we can all be a part of.

The pace of spinal cord research has been picking up steadily over the past few years and more teams are now working on repair treatments than ever before. What was once a trickle of applications for funding have now turned in to a flood!

This is good news of course but as more stories of research progress are reported in the media it becomes more difficult to get a grasp on what's happening. To help bring some of the confusion into focus Peter Banyard explains exactly where research is at the moment and what we can expect of the future.

AN OVERVIEW OF SPINAL CORD RESEARCH

The First Hours After Injury
When Spinal Research had its inception in 1981, a number of things were already known about the course of spinal cord injury. One of the most intriguing facts was that the nerve fibres within the cord's tough outer sheath are not severed at the time of the injury; unless they are physically cut by a knife or bullet wound. In the 24 hours after injury the nerve strands part and die back from the point of impact, and the original area of damage doubles in size. Clearly this presents a window of opportunity. If the remorseless progression of nerve fibre damage can be interrupted, the eventual degree of paralysis will be lessened.

Spinal Research has spent hundreds of thousands of pounds trying to produce a treatment for the first moments and hours after injury. We have had no success as yet, although we are still funding laboratory work in Germany and the US as well as the UK. We also know that one of our UK research laboratories is pursuing a very promising line of investigation, and this is likely to pay-off in the end.

Surviving Fibres
It is also well known that, even in apparently complete injuries, not all the long nerve fibres will be severed. Anything around 10% or so of surviving fibres descending from the brain can leave a patient walking and with little sign of injury. If 4% or less survive, the patient may be left with an apparently complete injury. Over 90% of all patients have some surviving fibres.

As far as we know, surviving fibres exist throughout a patient's lifespan, so there is a chance of treatment for the most long-standing injuries. Often the fibres that do survive have a curiously gnarled shape and have been stripped of their insulating sheaths. Our laboratory work has progressed to the stage at which we can restore the insulating sheath, which will surely improve the conduction of nerve signals. This is an area we have only begun to examine, and we intend to finance further investigation of it in the near future. Everyone can hope for some improvement in his/her condition when this work is completed.

After the Injury has Stabilised
The progress of paralysis and, in some cases, recovery from it, is more or less complete six months after injury. Those nerve fibres descending from the brain will stop and die back a short distance from the scar tissue around the injury site. In the same way, the ascending fibres, which give feeling, will stop on their way up through the sensory tract and die back from the injury site. However, and this is crucial for old lesions, the cells that support and insulate the vanished nerve fibres remain, lined up in tunnel-shaped tracts, waiting for the fibre to regrow. Sometimes they wait for years, sometimes throughout a lengthy lifespan, but this will not always be the case. In many patients, the cord will become much thinner after many years and we assume that this is because the tracts have collapsed. All the same, we believe that the majority of existing lesions can be helped if we can get those cut nerve fibres to regenerate; and we believe that we can now do that.

When Spinal Research was founded 21 years ago, there was already a nugget of information that would point the way forward to a successful treatment for spinal cord injury.

• Nerves outside the spinal cord do regrow after being cut
• When tissue from those nerves is grafted into spinal cord, the severed spinal cord fibres will readily grow along it. Unfortunately they stop when they reach a normal spinal cord environment at the end of the tissue graft.

So a normal spinal cord environment is hostile to regrowth, but tissue from the nerves outside the spinal cord does permit regrowth. By 1997 our grantholders had made two enormous strides forward.

1. The barrier to regrowth seemed to be in the scar tissue. If regrowing fibres could be piped through the scarred area and then, most importantly, into the surviving tracts on the other side of the lesion, they would regrow; and fast.
2. There is a specialist cell in the olfactory system (that gives us our sense of smell and taste) which will lead regrowing fibres into the surviving tracts.

Sorted, you might think, but it was not. The olfactory cells are few and a human lesion is large so they have to be persuaded to multiply in culture. We have had success with this but, from the point of view of clinical trials the difficulties are multiplied. No ethical or government licence is needed to graft tissue from one part of a patient to another. However, if the tissue is manipulated in culture or put into serum, it becomes a pharmaceutical; and then there is a long and expensive road through to clinical trials. Amongst other things, effectiveness in two mammalian species and purity have to be demonstrated.

We also have another promising repair agent. There are certain molecules that encourage regrowth. The first discovery of this was Nerve Growth Factor in the 1960s. For spinal cord repair, we are impressed with a more recently discovered molecule with the abbreviated name of NT3. When NT3 is placed in the lesion site in a laboratory model, the severed fibres start regrowing, pass through the NT3 and carry on through the tracts on the far side.

Spinal Research has developed a computer-controlled model of the typical human spinal cord lesion. We will be trying olfactory cells and NT3 on that model in the near future. If either or both succeed, it or they will be tried on a further mammalian species in preparation for clinical trials.

Meanwhile our Clinical Initiative is preparing for those trials. We are developing methods of assessing humans so that the slightest degree of nerve fibre regrowth can be detected. We want our results to be absolutely definite, leaving no room for dispute.

Finally, I hope that readers will realise that this has been no trivial endeavour. The Clinical Initiative alone will cost £1 million. The anxiety of raising the funds, the immense effort involved in planning research and maintaining business disciplines are not the casual gambler's throw of desperate people. We have done much and are proud of it. We could also do with help from those who share our hopes and will raise funds for us.

Peter Banyard
Chief Executive

COORDINATING THE RESEARCH EFFORT

The purpose of Spinal Research has always been to fund research into the repair of human spinal cord injuries. This research has been very successful, and has now reached the stage where some techniques for partial repair of spinal cord lesions have been demonstrated in animal models. It is probable that if the same techniques could be used in human spinal cord injury patients they would show an improvement in their condition, although not a complete cure. The first trials of these treatments on paralysed people are therefore now being contemplated.

As Europe's major spinal cord injury charity, Spinal Research sees it as its duty to help provide the infrastructure that will be necessary to make it possible for these experimental techniques to be applied to the treatment of paralysed people.

The Trust has started two new initiatives to make this possible; the Research Network and the Clinical Initiative.

Repair of spinal cord injuries will require a combination of several different treatments, and so the Trust has moved quickly to set up the Research Network to deal with this difficult task. All the laboratories funded by Spinal Research are part of this network, which holds regular meetings to co-ordinate the many strands of spinal injury research.

From within this network is drawn a group whose primary responsibility is to turn successful basic research into treatments for spinal injury victims. Taking basic research into the clinic is a major step, and Spinal Research will help this group to achieve it by encouraging research teams within the group to work closely together.

The Clinical Initiative is funding research into ways of assessing the improvements in human patients when the first spinal cord repairs are made. This is a crucial step, because the trials of treatments cannot be started until it is possible to make a proper assessment of the effects on the patients' disability.

Spinal Research is determined that patients with spinal cord injuries will receive treatments as soon as possible. These two initiatives will ensure that there is no delay in translating the successful basic research programme into effective treatments.

The Trust's Research Network is playing a crucial role in speeding up the process of moving from research into development. It is only possible to fund innovative projects like these because of the generous donations we receive from our supporters. This is why it is so important to support research in whatever way you can.

Spinal Research is about creating a better future; a future where spinal cord injury paralysis is a thing of the past; a future we can all be a part of.

Dr James Fawcett
Chairman of the Scientific Committee