After a spinal cord injury, severed nerve fibres must be forced to regrow through the dense molecular mesh that fills the space between cells—but they lack the biological grappling hooks needed to gain traction. This matters because no licensed treatment can repair a damaged spinal cord. When nerve fibres connecting the brain to the body are cut, patients suffer permanent paralysis and loss of sensation below the injury. First-generation regeneration treatments exist, but they work only partially. The researchers have identified a specific adhesion molecule—an integrin—that nerve fibres in the brain and spinal cord normally lack. Using genetic engineering, they plan to insert this integrin into nerve cells, ensure it reaches the growing fibre tips, and prevent inhibitory molecules in damaged tissue from switching it off. If this succeeds, the approach could trigger robust regrowth of severed spinal cord fibres, potentially restoring movement and sensation. The work is still at the fundamental science stage—no human trials are imminent—but it directly addresses a biological bottleneck that has stalled previous repair strategies.
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Repair of the damaged spinal cord and brain is a major unmet need in the treatment of neurological diseases, with no treatments currently licensed. After spinal injury the nerve fibres that connect the brain to the spinal cord are cut, leading to paralysis and loss of sensation in the body below the area of damage. In order for patients to regain function the nerve fibres must be made to regenerate so as to reconnect the brain to the body via the spinal cord. Several laboratories are working to develop treatments to enhance axon regeneration after spinal cord injury and various candidates have emerged. However these first-generation treatments are only partially effective. The programme will develop a new strategy for inducing nerve fibre regeneration. Regrowing nerve fibres have to penetrate the extracellular matrix that lies between cells. In order to gain traction on this material the nerve fibres must have adhesion molecules known as integrins that adhere to molecules in the matrix. Axons in the brain and spinal cord lack the integrin that is needed to interact with the spinal cord and brain extracellular matrix. We have found an integrin that solves this problem. In order to make it possible for this integrin to stimulate nerve fibre regeneration we have to use genetic engineering to place the molecule in nerve cells, then we have to ensure that the integrins can be transported into nerve fibres. In addition, inhibitory molecules in the damaged nervous system can turn off integrins, and we will develop methods to turn them back on. Together these interventions have the promise of stimulating robust regrowth of damaged spinal cord nerve fibres.
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