Efficacy of albendazole–GM6001 co-therapy against Angiostrongylus cantonensis-induced meningitis in BALB/c mice

Angiostrongylus cantonensis causes a form of parasitic meningitis in humans. Albendazole kills the nematode larvae staying in the brain. However, the dead larvae are capable of evoking a severe inflammatory response resulting in the brain damage. Matrix metalloproteinase 9 (MMP-9) is associated with the development of meningitis and with the immune inflammatory reaction. Presently, we studied the combination effects of albendazole and GM6001 (a MMP-9 inhibitor) against angiostrongyliasis in BALB/c mice. Co-administration of drugs produced marked effects; to kill the infecting larvae and to block MMP-9 activity. The combination treatment reduced MMP-9 activity by 89.2% in cerebrospinal fluid. The numbers of inflammatory cells increased significantly upon establishment of infection, but subsided upon co-treatment. Significantly fewer larvae were recovered from treated mice than from untreated, infected mice. The present results strongly suggest that co-therapy with albendazole and GM6001 may be an useful approach for the treatment of human angiostrongyliasis.