Spinal cord repair research

Research into spinal cord repair has made enormous progress in recent years. Spinal Research now hopes for the regeneration of four centimetres of spinal cord in a paralysed person. Those four centimetres could potentially help a seriously paralysed person breathe unaided, or regain the use of his or her arms.The neurons forming the spinal cord are highly vulnerable to damage if vertebrae of the spinal column are subjected to a severe shock or impact. Unlike nerve fibres in other parts of the body, they do not have a natural ability to regrow if they are cut or damaged. Spinal cord neurons do not repair themselves.

A number of complementary research routes show particular promise for the successful treatment of spinal cord injury. Spinal Research calls them the Routes to the 4cm Future and they form the basis of research leading to the planned clinical trials.Minimising the initial damage - Neuroprotection Most spinal injuries do not completely sever the spinal cord outright. In most cases, some neurons in the surrounding area remain intact, at least initially. However, when neurons in the spine die, they send out signals that cause neighbouring, uninjured neurons to die. This enlarges the damaged area and can double the size of the affected area in the first few hours after injury. It also causes scar tissue to accumulate at the injury site. Scientists are now investigating ways of reducing the spread of secondary damage at an early stage – soon after the injury has occurred, thus reducing the scale of the injury and its long-term consequences. Removing barriers – Chondroitinase treatment Chondroitinase is an enzyme that partially removes the otherwise impenetrable barriers formed by the scar tissue around a spinal cord injury, allowing regenerating nerve fibres to pass through.In the months following injury to the spinal cord, the loss of neurons is accompanied by the formation of scar tissue that gradually fills the damaged area.

Scar tissue is a major obstacle to regeneration because it contains several molecules that inhibit neuronal growth. With backing from Spinal Research, researchers have dissolved away vital parts of these growth inhibitors. Consequently, neurons have grown through the scarred region to undamaged tissue beyond. Neuronal growth of up to 4mm has been measured in laboratory models, accompanied by increases in sensation, muscle coordination and walking. Combating blockers – Counteracting NogoAntibodies have been developed to counteract the effects of Nogo, a family of molecules that prevent the regrowth of nerve fibres in the spinal cord. Preventing inhibition of regrowth In mature mammals, the brain and spinal cord contain powerful inhibitory factors that prevent nerve growth. These factors are designed to have a protective role, preventing nerves from growing inappropriately after normal neuronal connections have developed. Following injury, however, these same inhibitory factors prevent repair processes from starting.

Scientists have now developed an antibody that combines with Nogo and neutralises it before it interacts with neurons. This prevents these inhibitory effects and increases neural regeneration.Filling the gap – Tissue engineeringNewly developed biocompatible materials can form a bridge across the damaged region and provide the optimum environment for regrowth of nerve fibres, blood vessels and supporting tissues. Tissue grafts help fill the cavities inside the spinal cord that are created by injury. This approach aims to bridge the gap between the damaged ends of neurons on either side of a spinal cord injury. It does this by transplanting artificial guidance channels into the spinal cord. These provide a physical support along which neurons can regrow. The guidance channels direct growth across the damaged area and protect neurons from barrier-forming scar tissue. Incorporating growth factors into the new tissue ‘scaffolding’ can further boost the regeneration of neurons.Nurturing regrowth - Olfactory gliaOlfactory glia are unique cells that exist in the olfactory system (responsible for the sensation of smell), where they guide and protect newly-forming nerve fibres. When transplanted into the damaged spinal cord, they aid the regeneration of nerve fibres.

In humans, the nerves that transmit the sensation of smell from the nose to the brain - unlike those in the brain and spinal cord - are replaced naturally throughout life. They also regrow after injury. Olfactory nerves do this because they are surrounded by specialised cells, called olfactory glia, which form a protective myelin coating around the nerves. Olfactory glia do not occur naturally in the spinal cord. However, with funding from Spinal Research, laboratory researchers have transplanted olfactory glia into spinal cord injuries. Results have conpracticeed that the glia have a regenerative effect on the damaged spinal cord. In addition, myelin is essential for the rapid transmission of nerve signals. It can degenerate after spinal cord injury, with the result that undamaged neurons no longer function efficiently. Therefore, using olfactory glia to restore the myelin coating could boost the performance of the neurons that remain following injury.Stimulating and guiding – Neurotrophic factorsNeurotrophic factors (also called growth factors) are molecules that are involved in stimulating and guiding the growth of nerve fibres, encouraging regeneration in damaged areas of the spinal cord.

Scientists funded by Spinal Research are finding ways to make the damaged ends of neurons regenerate and form sprouts that grow through the damaged region. They are using growth factors to do this.In the course of normal human development, growth factors play a vital role. They stimulate the cells that are programmed to form neurons in the spinal cord, causing them to divide and grow. Many growth factors also attract growing neurons to areas that contain the highest concentrations of growth factor, thereby directing neurons to their appropriate target regions.

Spinal Research is funding investigation into the most effective growth factors and the best ways to introduce them into the injured spinal cord.Replacing damaged cells – Stem cellsStem cells have the potential to develop into every type of cell in the body. In future, stem cells might be used to replace the neurons and glial cells that die after spinal cord injury. Human life begins as a single cell that is formed when the father's sperm fuses with the mother's egg. This initial cell then divides to form a ball of cells: the cells on the outside of this ball form the placenta, whereas those inside the ball are embryonic stem cells. All of the cells in the body, from liver cells to neurons, come from the division of embryonic stem cells.Scientific research using embryonic stem cells is still at quite an early stage. Obviously there are ethical considerations with any research that involves cells from embryos, but research for therapeutic purposes - such as the development of treatments for spinal cord injury - is legally allowed.

Using cells from adults would overcome ethical concerns, but research on adult stem cells is much less advanced. Stem cells hold great potential for the treatment of spinal cord injury. Because they can develop into every type of cell, they could, in principle, be used to replace all the damaged tissue in the spinal cord. However, scientists do not yet understand how to control stem cells and make them turn into the required cell types. At present stem cells that are transplanted into spinal injuries mostly develop into the cells that make scar tissue.Spinal Research supports stem cell studies. It is not directly funding projects on this topic at present because priorities are in other areas, but expects to do so in the future.

Source - Spinal research

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