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Encouraging neuroplasticity after a spinal cord injury
Neuroplasticity is the ability of the brain to continuously change throughout one's life - to the extent that brain activity associated with a given function can be transferred to a different location. However, after spinal cord injury the degrees and extent of neuroplasticity and recovery depend on a number of different factors, not all within any individuals control. As an area fundamental to recovery, Spinal Research is funding a number of trials with neuroplasticity at their heart.
What You're Funding
In line with our strategy for research, we are supporting a variety of different trials which are in a variety of different stages. This is to ensure we continue hitting critical milestones and overcoming many of the issues related to creating safe therapies. These range from a PhD studentship that follows on from previous findings, innovative investigations in areas that are yet to see any effective therapeutic strategies, and a confirmatory study on the efficacy of chondroitinase - the incredibly promising enzyme that has been shown to break down scar tissue.
Dr Jessica Kwok (Leeds University): Oral administration of a novel plasticity enhancer in chronic spinal cord injury
The project will focus on a small molecule, PNNi, which has been shown to reduce the perineuronal net in a normal spinal cord. Perineuronal nets are crucial in stabilising synaptic connections and shaping neural circuitry, controlling neural plasticity during the development of the central nervous system and after injury in an adult. This research seeks to discover if treatment with PNNi is effective in chronic injuries: will it lead to the down-regulation of perineuronal nets, enhancing plasticity and allowing the formation of new functional synapses for recovery? It will also gather important information on the efficacy of this drug in decreasing the inhibitory activity of the perineuronal net and enhancing axon sprouting.
Because PNNi is already licensed to treat biliary stasis it could easily be repurposed as a treatment, one that is non-invasive and can be switched off easily by simply not taking the medication. If successful this drug will benefit not only newly injured patients but also those who have a chronic injury.
Dr Yu Shang Lee (Lerner Research Institute, Cleveland Clinic): A translatable peptide reduces glial scar to repair chronic spinal cord injury
The proposed project will investigate a highly translational repair strategy using an innovative peptide to treat rats with chronic spinal cord injury. In this preclinical study, the efficacy of treatments will be evaluated using both locomotion and bladder control, in line with patient's high priorities. It will build on previous research that has shown how a small peptide (CRP) has been shown to reduce the main component of the glial scar tissue (CSPG) that grows near the injury site and leads to poor nerve regrowth capacity and poor functional outcomes after an injury.
Thus, this project will test whether CRP (or CRP combined with another peptide, ISP) can improve functional outcomes in rats with chronic T8 contusive SCI; and then, will it also enhance the regeneration/sprouting of descending nerve fiber systems.
Professor Liz Bradbury (King's College London) and Joost Verhaagen (Netherlands Institute for Neuroscience): Creating a safe gene therapy to treat spinal cord injury
Since a discovery in the 1990's that chondroitinase could digest the scar tissue that develops as both a physical and chemical barrier to nerves after a spinal cord injury, this bacterial enzyme has been studied extensively. And great progress towards finding a clinically-testable gene therapy treatment has been made since then, particularly following on from our CHASE-IT consortium which launched in 2014. Our current work builds on all this previous research by seeking to finally design a clinically acceptable gene therapy treatment that can be tested in clinical trials. Three key aims will be addressed here: test the principle that chondroitinase is still effective when administered in a chronic spinal cord injury; engineer a regulatable adeno-associated viral vector; and test the regulatable chondroitinase adeno-associated viral vector in vivo.