Integrins as a therapeutic tool for CNS repair

修复受损的脊髓和大脑是神经系统疾病治疗中一个主要的未满足的需求，目前还没有获得许可的治疗方法。脊髓损伤后，连接大脑和脊髓的神经纤维被切断，导致受损区域以下的身体瘫痪和失去知觉。为了使病人恢复功能，必须使神经纤维再生，以便通过脊髓将大脑与身体重新连接起来。几个实验室正在努力开发治疗方法，以增强脊髓损伤后轴突的再生，各种候选已经出现。然而，这些第一代治疗方法只是部分有效。该项目将开发一种诱导神经纤维再生的新策略。再生的神经纤维必须穿透细胞间的细胞外基质。为了在这种材料上获得牵引力，神经纤维必须具有粘附分子，称为整合素，粘附在基质中的分子上。脑和脊髓中的轴突缺乏与脊髓和脑细胞外基质相互作用所需的整合素。我们已经找到了一个可以解决这个问题的积分素。为了使这种整合素刺激神经纤维再生成为可能，我们必须使用基因工程将分子置于神经细胞中，然后我们必须确保整合素可以运输到神经纤维中。此外，受损神经系统中的抑制分子可以关闭整合素，我们将开发使其重新启动的方法。总之，这些干预措施有望刺激受损脊髓神经纤维的强劲再生。

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.