Title: Microtubule-stabilizing drugs suppress convulsions in a C. elegans model of CAMSAP disorders.

Recessive, loss of function, genomic variants in CAMSAP1 and 2 (calmodulin-regulated spectrin-associated proteins 1 and 2) cause a neurodevelopmental seizure disorder in humans that currently lacks specific treatments. CAMSAP proteins stabilize dynamics of the minus-ends of microtubules and regulate regenerative signaling cascades. We explored microtubule-stabilizing drugs as potential therapeutic interventions using a convulsion assay in the model organism Caenorhabditis elegans . We found that animals with genetically disrupted ptrn-1 (the C. elegans homolog of CAMSAP1 ) exhibited elevated convulsion frequency relative to wild type, and that Epothilone B and Valproic Acid reduced convulsions. We also found that Paclitaxel increased convulsions, and Davunetide produced variable outcomes. These results suggest that pharmacologic microtubule stabilization is a promising strategy for diseases caused by genetic disruption to CAMSAP function. • Genetic disruption of CAMSAP homolog increases convulsion frequency in C. elegans . • Pharmacologic stabilization of microtubules reduces convulsions in C. elegans model • Epothiolone B and Davunetide reduce convulsions for CAMSAP ( ptrn-1 ) worms • Development of C. elegans model for CAMSAP seizure disorder drug screening