October 17, 2014
Identifying Compounds with Therapeutic Potential for Paclitaxel-Induced Peripheral Neuropathy
Peripheral neuropathy, the uncomfortable and often painful degeneration of peripheral nerve endings, can be induced in humans by chemotherapeutic agents such as paclitaxel (PTX). The impairment of axonal regeneration is exhibited in the paclitaxel-treated larval zebrafish, providing a model for paclitaxel-induced peripheral neuropathy (PIPN). With such a model, I aimed to prevent or reverse paclitaxel’s detrimental effects on neurons by performing a chemical screen to identify compounds with therapeutic potential. Previous studies revealed that endogenous production of hydrogen peroxide is necessary for axon regeneration, highlighting this compound as therapeutically interesting for PIPN. Here I show that low concentrations of exogenous H2O2 rescue injury-induced regeneration of axons in the presence of paclitaxel treatment. CL-82198, a pharmaceutical regulator of a gene upregulated in the presence of H2O2, also rescues axonal regeneration. I conducted this research on an REU fellowship from NSF at Mount Desert Island Biological Laboratory, a campus that provided a diverse yet intimate community to foster a unique collaborative experience for students and scientists alike.