The first clinical trials seeking to repair spinal cord injury on a pilot group of selected patients are set to begin at University College London (UCL) within the next three years, says Professor Geoffrey Raisman, director of the newly established Spinal Repair Unit at UCL. Professor Raisman will be setting out his vision for the future in New York on Thursday 20th January, at the US launch of the Campaign for UCL, a major campaign with the objective of raising funds necessary to support projects that include development of the Spinal Repair Unit.
Professor Raisman was one of the first neuroscientists whose work in stem cell research has raised the real possibility that spinal cord injuries, long considered incurable, could be repaired. The work of the team holds out significant hope that spinal cord patients will eventually be able to regain much of the ability to move that they have lost. For paraplegic patients this could lead to a return of sensation and movement to some leg muscles, potentially allowing them to stand and making movement easier, while tetraplegics (patients with spinal injury high in the neck region), could recover touch sensation and movement of the hands, and regain the ability to dress, feed and clean independently.
Professor Raisman's key discovery was that there is one part of the nervous system, a region in the nasal cavity concerned with the sense of smell, in which nerve fibres are in a state of continuous growth throughout adult life. Working at the National Institute for Medicial Research in London, Raisman's team transplanted cells from this region into the injured spinal cord of laboratory rats, and found that the cells had a remarkable capacity to integrate into damaged pathways, laying a 'bridge' over the gap in the nerve fibres caused by injury.
The team has now moved to UCL to attempt to transfer that technology from rats to humans, working with patients at the National Hospital for Neurology and Neurosurgery in London, and it is anticipated that the preparatory work to begin trials will be complete within two to three years.
"For many years these injuries were considered incurable, and they are still are incurable," says Professor Raisman, "But I believe that we can now affirm that the door leading to repair of such injuries has now been opened, even if it is for the time being only ajar."
The devastating effects of spinal cord injury are due to disconnection of nerve fibres. Disconnection of the nerve fibres travelling from the brain down to the spinal cord causes paralysis, loss of control of the bladder and bowels, and loss of sexual functions. It can also prevent breathing. Disconnection of nerve fibres travelling up to the brain causes loss of sensation.
"When a nerve fibre is severed it attempts to regrow, like the sprouts arising from the trunk of a felled tree," says Professor Raisman, explaining the technique that his team have discovered. Their failure to do this is not due to an intrinsic inability of nerve fibres to grow, but to the disruption of the pathway along which the nerve fibres need to travel in order to reach their original destinations. This realisation has led to a completely new approach to repairing spinal cord injury.
"It is as if part of a roadway has been washed away by a flooding river. The cars are still able to travel, the drivers remember where they wish to go, the tanks are full of fuel. The situation will not be repaired by adding more cars, or filling up the tanks to overflowing. What is required is to repair the roadway, to lay a bridge over the gap.
"The pathway taken by nerve fibres is a living pathway made up of specialised cells laid out in rows, like the paving stones of a road. When the spinal cord is injured, the pathway cells of the spinal cord are unable to repair themselves. They remain piled up in a great scar. The scar has the value of holding the flood water back but forms an impenetrable barrier to the cars.
"The way out of the impasse came from the discovery that there is one part of the nervous system, and only one, in which nerve fibres are in a state of continuous growth throughout adult life. This is the part of the nervous system concerned with the sense of smell. It is located in the upper part of the lining of the nasal cavity and contains adult stem cells which are capable of regenerating the entire system. The intuitive leap was to transplant cells obtained from this area into the injured spinal cord. What we found was that in laboratory animals the cells have a remarkable capacity to integrate into the damaged roadway, open up the scar, and lay a bridge over the gap.
"The cut nerve fibres at once recognised the bridge, crossed it rapidly, and regenerated to their original destinations. In laboratory animals these transplants resulted in return of important functions such as paw reaching and climbing, and we were the first, and still the only, team to show that this repair resulted in a restoration of the ability to breathe. Very promising ongoing studies are investigating whether this approach can also restore bladder, bowel and sexual functions.
"An especially encouraging feature of these transplants, carried out in laboratory animals, is that the reparative pathway cells can be obtained from tissue samples taken from the adult nasal lining by a technique which does no permanent damage, since the system, like skin, contains adult stem cells and is in a state of continuous self renewal. If this technique can be transferred to humans, the patient can be his/her own cell donor. This will avoid the need to use embryonic tissue, to find donor individuals, foreign stem cells, or to use powerful designer drugs with unknown side-effects.
"The ability to reconnect spinal cord nerve fibre is only a beginning. Success will open the door to a number of other conditions where nerve fibres are damaged. These include some major forms of stroke, as well as blindness and deafness caused by nerve injuries. There is a long way to go, and we do not wish to raise false hopes in patients who are living with spinal cord injury. However, our work to date clearly indicates that, contrary to received wisdom, the spinal cord does have the potential to repair itself. That is why we believe that human trials are the logical next step."
"Professor Raisman and his team have shown that the repair of the injured spinal cord is now a real possibility," says Professor Malcolm Grant, President and Provost of UCL. "Bringing the team to UCL means that we can now start preparing for the day when the first trials will begin. We all look forward to seeing this promising research translated into successful clinical trials at the earliest possible stage. We are launching our Campaign for UCL in New York this week to showcase and gain support for the groundbreaking research talking place across UCL, of which the work of Professor Raisman's team is one example."
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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