Interleukin 37: a novel therapeutic approach for the treatment of acute spinal cord injury
Funded in: 2017, 2018, 2019, 2020
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Problem: The inflammation of the injured spinal cord causes additional damage and worsens functional recovery.
Target: IL-37, a cytokine member of the IL-1 family
Goal: Development of IL-37 as a new treatment for acute spinal cord injury
Introduction: Spinal cord injury (SCI) leads to devastating permanent disabilities in thousands of people each year. Research performed during the last decade has shown that the inflammation that occurs in the injured spinal cord causes additional damage and worsens functional recovery.
Problem statement: Although inflammation is detrimental to recovery after SCI, clinical trials of high doses of methylprednisolone have not been successful. There is therefore a need to develop better anti-inflammatory therapies. We have recently reported that mice expressing human IL-37, a, exhibit reduced inflammation after SCI and improved locomotor recovery. However, we still do not know how IL-37 works to reduce inflammation and improve function.
Methods and expected results: IL-37 binds to a receptor on the surface of cells (extracellular), but can also work within the nucleus of the cell where DNA is located (intracellular). Thus, we will generate different genetically modified mice that will allows us to dissect to what extent the beneficial actions of this cytokine in the lesioned spinal cord are produced by its extracellular or intracellular actions. Moreover, we also plan to develop and test more effective recombinant forms of IL-37 in animal models of SCI. We expect that these recombinant forms of IL-37 will be much more effective in improving neurological outcomes after SCI.
Potential application: Development of IL-37 as a new treatment for acute spinal cord injury.