A new approach to promote axonal regrowth after spinal cord injury by combining self-assembling Fmoc-based hydrogels with Epac2 activation

Spinal injury affects 50,000 people in the UK, with roughly 1,000 new cases annually, and causes permanent and incurable functional impairment below the injury site. Due to the complex nature of spinal injury, which includes a physical and molecular barrier to nerve regeneration, no single therapy has ever been successful, so a combined approach is much more likely to be effective. Our pilot research, using tissue culture experiments, demonstrates: 1) a novel, nerve growth-supporting, injectable hydrogel is suitable for spinal repair as a physical scaffold; 2) nerve growth is increased by adding a drug that activates a growth-promoting protein called Epac2 in nerve cells; and 3) drug-induced Epac2 activation prevents potent inhibition by molecules in the injury site, further encouraging nerve growth. The proposed project aims to develop a novel combinatorial strategy by using the hydrogel as a depot from which the Epac2 activating drug can be released into the local injury site to promote spinal nerve regrowth. The project will exploit state-of-the-art live cell imaging, alongside genetic, neurochemical, and behavioural tools in clinically relevant mammalian spinal injury models. Furthermore, by providing a path towards an effective and easily administered treatment, it will have an impact on clinical neuro-regenerative strategies.