Integrins as a therapeutic tool for CNS repair

修复受损的脊髓和大脑是神经疾病治疗中一个尚未得到满足的主要需求，目前还没有获得许可的治疗方法。脊椎损伤后，连接大脑和脊髓的神经纤维被切断，导致损伤区域以下的身体瘫痪和感觉丧失。为了让患者恢复功能，神经纤维必须再生，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脊髓损伤后促进轴突再生的方法，并出现了各种候选方案。然而，这些第一代治疗方法只有部分有效。该计划将开发一种诱导神经纤维再生的新战略。再生的神经纤维必须穿透位于细胞之间的细胞外基质。为了获得对这种材料的牵引力，神经纤维必须有被称为整合素的黏附分子，这种黏附分子附着在基质中的分子上。大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。我们已经找到了一种解决这个问题的整合素。为了使这种整合素能够刺激神经纤维再生，我们必须使用基因工程将分子放置在神经细胞中，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，我们将开发方法重新启动它们。总而言之，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.