Repositioning Flubendazole for Spinal Cord Injury

Authors: Yu CG1Bondada V2Ghoshal S3Singh R4Pistilli CK5Dayaram K6Iqbal H7Sands M8Davis K9Bondada S10Geddes JW11   University of Kentucky Spinal Cord and Brain Injury Research Center

Lab Abstract

We previously reported the serendipitous observation that Fenbendazole, a benzimidazole anthelmintic, improved functional and pathological outcomes following thoracic spinal cord contusion injury in mice when administered pre-injury. Fenbendazole is widely used in veterinary medicine. However, it is not approved for human use and it was uncertain if only post-injury administration would offer similar benefits. In the present study we evaluated post-injury administration of a closely related, human anthelmintic drug, Flubendazole, using a rat spinal cord contusion injury model. Flubendazole, administered IP, 5 or 10 mg/kg day, beginning 3 hrs postinjury and daily thereafter for 2 or 4 weeks, resulted in improved locomotor function after contusion SCI compared to vehicle-treated controls. Histological analysis of spinal cord sections showed that such treatment with Flubendazole also reduced lesion volume, improved total tissue sparing, white matter sparing, and gray matter sparing. Flubendazole inhibited the activation of GFAP, suppressed cyclin B1 expression and Bruton’s tyrosine kinase activation, markers of B cell proliferation and inflammation, and reduced B cell autoimmune response. Together, these results suggest the use of the benzimidazole anthelmintic Flubendazole as a potential therapeutic for spinal cord injury.

 2019 Feb 12. doi: 10.1089/neu.2018.6160. [Epub ahead of print] Jan 3.


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