# (PQ#9) Promoting Axon Stability to Prevent Therapy-induced Peripheral Neuropathy

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2021 · $465,400

## Abstract

Project Summary/Abstract:
 Therapy-induced peripheral neuropathy (TIPN) is a very common and often dose-limiting side effect of
anti-cancer therapy. Clinically, TIPN is a predominantly sensory peripheral neuropathy characterized by
numbness, tingling, and often, neuropathic pain. These symptoms can persist for years after cessation of
treatment, and so TIPN can significantly diminish patient's quality-of-life both during and after treatment.
Moreover, the development of TIPN often necessitates reducing drug dosage or switching regimens, and
therefore limits the effectiveness of anti-cancer therapy. Currently, there are no effective treatments for TIPN.
Axon loss is a hallmark of this neuropathy, suggesting that mechanistically distinct chemotherapeutics may
feed into a common axonal degeneration program. We have demonstrated that genetic inhibition of SARM1,
the central executioner of this core axonal degeneration program, blocks the development of TIPN in a mouse
model of vincristine-induced peripheral neuropathy. The SARM1 pathway induces axon loss by triggering
depletion of the essential metabolic co-factor NAD. Here we seek to block the development of TIPN by
countering this loss of NAD in order to maintain axonal health. We also explore mechanisms to block the
activation of SARM1 as novel therapeutic strategies for blocking the development of TIPN. Finally, targeting
the SARM1 pathway will be a useful treatment for TIPN if manipulating this pathway does not affect tumor
growth or chemotherapeutic efficacy. We will explore this using genetic tumor models. If successful, this
project will identify novel treatment strategies for the prevention of TIPN.

## Key facts

- **NIH application ID:** 10227703
- **Project number:** 5R01CA219866-05
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Aaron Diantonio
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $465,400
- **Award type:** 5
- **Project period:** 2017-08-16 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10227703

## Citation

> US National Institutes of Health, RePORTER application 10227703, (PQ#9) Promoting Axon Stability to Prevent Therapy-induced Peripheral Neuropathy (5R01CA219866-05). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10227703. Licensed CC0.

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