Identification of fluocinolone acetonide to prevent paclitaxel-induced peripheral neuropathy

Aysel Cetinkaya-Fisgin; Min Geol Joo; Xiang Ping; Nitish V Thakor; Cengizhan Ozturk; Ahmet Hoke; In Hong Yang

doi:10.1111/jns.12172

Identification of fluocinolone acetonide to prevent paclitaxel-induced peripheral neuropathy

J Peripher Nerv Syst. 2016 Sep;21(3):128-33. doi: 10.1111/jns.12172.

Authors

Aysel Cetinkaya-Fisgin^{1

2}, Min Geol Joo³, Xiang Ping⁴, Nitish V Thakor^{4

5}, Cengizhan Ozturk¹, Ahmet Hoke², In Hong Yang^{4

5}

Affiliations

¹ Institute of Biomedical Engineering, Bogazici University, Istanbul, Turkey.
² Department of Neurology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
³ Department of Biomedical Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA.
⁴ Singapore Institute for Neurotechnology, National University of Singapore, Singapore, Singapore.
⁵ Department of Biomedical Engineering, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.

PMID: 27117347
DOI: 10.1111/jns.12172

Abstract

Paclitaxel (PTX) is among the most commonly used cancer drugs that cause chemotherapy-induced peripheral neuropathy (CIPN), a debilitating and serious dose-limiting side effect. Currently, no drugs exist to prevent CIPN, and symptomatic therapy is often ineffective. In order to identify therapeutic candidates to prevent axonal degeneration induced by PTX, we carried out a phenotypic drug screening using primary rodent dorsal root ganglion sensory neurons. We identified fluocinolone acetonide as a neuroprotective compound and verified it through secondary screens. Furthermore, we showed its efficacy in a mouse model of PTX-induced peripheral neuropathy and confirmed with four different cancer cell lines that fluocinolone acetonide does not interfere with PTX's antitumor activity. Our study identifies fluocinolone acetonide as a potential therapy to prevent CIPN caused by PTX.

Keywords: chemotherapy-induced peripheral neuropathy; fluocinolone acetonide; paclitaxel; phenotypic drug screening.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Animals, Newborn
Anti-Inflammatory Agents / pharmacology
Anti-Inflammatory Agents / therapeutic use*
Antineoplastic Agents, Phytogenic / adverse effects
Axons / drug effects
Axons / pathology
Cell Line, Tumor
Cells, Cultured
Disease Models, Animal
Dose-Response Relationship, Drug
Embryo, Mammalian
Female
Fluocinolone Acetonide / pharmacology
Fluocinolone Acetonide / therapeutic use*
Ganglia, Spinal / cytology
Mice
Nerve Fibers / drug effects
Nerve Fibers / pathology
Neurons / drug effects
Paclitaxel / adverse effects*
Peripheral Nervous System Diseases / chemically induced*
Peripheral Nervous System Diseases / prevention & control*
Rats
Rats, Sprague-Dawley

Substances

Anti-Inflammatory Agents
Antineoplastic Agents, Phytogenic
Fluocinolone Acetonide
Paclitaxel