# (PQ12) Peroxisome proliferator-activated receptor alpha agonists as potential treatment for chemotherapy-induced peripheral neuropathy

> **NIH NIH R01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2020 · $324,275

## Abstract

Paclitaxel is a drug commonly used for the treatment of breast, lung, and ovarian cancer.
Peripheral neuropathic pain (CIPN) is one of the most common and serious adverse
effects experienced by cancer patients treated with paclitaxel. CIPN can be a dose-
limiting factor for chemotherapy, leading to premature termination of treatment, thereby
influencing survival and quality of life. Currently, no therapies have been identified that
address the underlying pathogenic mechanisms such as neurodegeneration; in fact, the
current symptomatic therapies are frequently ineffective in mitigating the painful
symptoms of CIPN in the majority of patients. Therefore, the identification of alternative
forms of therapy is a crucial medical need. In this application we focus on agonists of
peroxisome proliferator-activated receptor alpha (PPARα) as molecules of potential
therapeutic value for suppression of CIPN induced by paclitaxel. The PPARα receptors
are expressed by central and peripheral neuronal cells (dorsal root ganglia) involved in
pain transmission and by macrophages and other cells immune involved in the
inflammatory responses. In Aim 1, we will test whether fenofibrate, a clinically used non-
selective and weak PPARα agonist, prevents CIPN in the mouse paclitaxel model in
naïve mice. In Aim 2, we will characterize the potential of more selective novel PPARα
agonists and modulators to prevent and suppress CIPN induced by paclitaxel in naïve
mice. In Aim 3, we will assess the influence of these PPARα agonists on growth and
susceptibility to chemotherapy (paclitaxel) in non-small cell lung tumors in culture, in
patient derived tumor cells in culture and in tumor bearing animals. If effective
treatment/prevention can be identified, it should be possible to extend the treatment of
patients with drugs such as paclitaxel and platinum based compounds, as dose-
dependent neuropathy will no longer limit the utility of these therapies.

## Key facts

- **NIH application ID:** 9965862
- **Project number:** 5R01CA219637-03
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** M. Imad Damaj
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $324,275
- **Award type:** 5
- **Project period:** 2018-07-25 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9965862

## Citation

> US National Institutes of Health, RePORTER application 9965862, (PQ12) Peroxisome proliferator-activated receptor alpha agonists as potential treatment for chemotherapy-induced peripheral neuropathy (5R01CA219637-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9965862. Licensed CC0.

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