Inhibiting miR-155 in mice to improve repair after spinal cord injury
Funded in: 2016, 2017, 2018
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Problem: Spinal cord repair is limited by an exaggerated immune response and by a poor axon growth response
Target: micro RNA-155, a proinflammatory mediator inhibitor of axon growth
Goal: A therapeutic strategy to reduce secondary damage and improve axon growth
Introduction: Spinal cord injury causes long-lasting damage to nerve connections (axons) that communicate between the brain and the body. These injured axons cannot send information or repair themselves, causing paralysis and other complications. Spinal cord repair is prevented by several processes, including a massive immune response that worsens injury (“secondary damage”) and a poor growth response of injured axons.
Problem Statement: Spinal cord repair is limited by an exaggerated immune response and by a poor axon growth response. One potential therapeutic target is a microRNA called miR-155, which both activates immune cells and prevents axon growth. Here, we hypothesize that treatment of spinal cord injured mice with miR-155 inhibitor will reduce inflammation and secondary damage, improve axon growth, and enhance functional recovery (walking).
Methods and Expected Results: First, immune and nerve cells will be cultured to determine whether miR-155 inhibitor improves how these cells respond. We expect that immune cells (“macrophages”) treated with the inhibitor will be less toxic and more protective. We predict that nerve cells treated with miR-155 inhibitor will improve axon growth. When macrophages and nerve cells are grown together with miR-155 inhibitor, we expect that more nerve cells will survive and that they will extend longer axons.
Next, a mouse model of spinal cord injury will be used with miR-155 inhibitor. Mice will be subjected to control surgery or spinal cord injury; then, the mice will be treated with miR-155 inhibitor (or control solution). We predict that miR-155 inhibitor will reduce secondary damage and improve axon growth. We expect that miR-155 inhibitor will improve functional recovery (walking).
Potential Application: Inhibiting miR-155 is a potential therapeutic strategy that could improve spinal cord repair via two parallel pathways. microRNA inhibitors are in clinical testing and we use a translatable rodent spinal cord injury model, highlighting our proposal’s clinical relevance.