Some spontaneous nerve regeneration seems to take place after spinal cord injury (SCI), but this is limited in effect and very short range. Long range regeneration has proved difficult and our two recently approved projects specifically aim to overcome this problem.
After SCI, connections between nerve cells in the brain and those in the spinal cord are severed and fail to grow back. We know that a program to re-grow nerve fibres exists because it is activated after nerve injury elsewhere in the body, where there seems to be a kind of ‘switch’ for this program that is somehow not triggered in the spinal cord. This project will aim to promote regeneration in the spinal cord by intervening to fully activate this growth switch in injured neurons. The eventual aim of this project is to develop a therapy which will promote nerve axon regeneration over longer distances within the spinal cord, using a gene therapy approach. If this can be realised in animal models, the next step will be to develop a clinically usable form of the therapy. The achievement of long-distance regeneration would be expected to bring significant clinical benefits.
This project will combine new techniques to minimise the harmful effects of early trauma and promote regeneration by reducing inhibitory effects. Following SCI, the lesion site is dominated by macrophages, a type of white blood cells that are a key part of the immune response but that represent a significant barrier to recovery. There are two types of macrophage; type M1 which is extremely toxic and type M2 which promotes long-distance nerve axon growth. The researchers have discovered that exposure to cytokines (a type of protein) results in the macrophage types switching from one to another. This project will induce a conversion of macrophage to the very favourable M2 state and test whether this provides neuro-protection and enhanced regeneration. The delivery method needed for this treatment is also very safe, which means that, if the project is successful, a new treatment could be administered within hours following SCI. This project will also offer a great career development to a former Spinal Research PhD student, Jodie Hall (pictured right) – who after her training is now a co-supervisor in this project. Well done Jodie!