The role of ErbB inhibitors in promoting nerve regeneration in a mouse model of nerve injury

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Peller, Jacob
nerve regeneration , nerve injury , ErbB inhibitors , lapatinib , gefitinib
Nerve injury is a common clinical challenge that has a considerable impact on an individual’s quality of life and function. Despite multiple surgical strategies, functional outcomes following nerve injury remain poor. Increasing the rate at which axons regenerate could profoundly improve the success of recovery. The goal of this thesis was to investigate whether the dual ErbB1-ErbB2 inhibitor lapatinib or the ErbB1 inhibitor gefitinib could promote nerve regeneration in both in vivo and in vitro models. Using a mouse transection and repair sciatic nerve injury model, lapatinib was found to increase the number of regenerated myelinated axons at 28 days following nerve repair. For elucidation of the molecular pathway that could be promoting nerve regeneration, in vivo neurite growth assays interestingly demonstrated that gefitinib, more than lapatinib rescued the inhibitory effects by chondroitin sulfate proteoglycan on neurite growth. Furthermore, a mouse forelimb model of nerve injury was characterized which can be used to study the cellular and molecular effects of ErbB inhibitors in transgenic mice. The repurposing of ErbB inhibitors to enhance nerve regeneration requires further study to determine whether this therapy could be translated to improve functional recovery in people with nerve injury.
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