# NICOTINAMIDE RIBOSIDE FOR THE TREATMENT OF CHEMOTHERAPY-INDUCED NEUROPATHY, DRY EYE SYNDROME, AND HEARING LOSS

> **NIH VA I21** · IOWA CITY VA MEDICAL CENTER · 2021 · —

## Abstract

Continuing advances in detection and treatment have greatly increased the number of cancer survivors, as
well as more Veterans living with cancer because of continued therapy. However, while these therapies
prolong life, they are accompanied by adverse effects that introduce functional limitations and significantly
reduce quality of life of Veterans. For example, taxane and platinum-based chemotherapies produce very
painful and debilitating peripheral neuropathies that greatly diminish patients’ quality of life. These agents can
also cause dry eye syndrome (DES), and in the case of platinum-based therapies, hearing loss and tinnitus
due to ototoxicity in 40-80% of adults. Currently, no effective treatment exists to reduce the incidence of these
debilitating side effects of therapy and they remain a significant unmet need in healthcare. In recent years,
evidence has accrued that nicotinamide adenine dinucleotide (NAD+), an essential redox coenzyme, plays an
important role in protection against axonal injury. This laboratory recently demonstrated that a naturally
occurring vitamin B3 precursor of NAD+, nicotinamide riboside (NR; NIAGEN®) can both prevent and reverse
paclitaxel-induced peripheral neuropathy in rodents. The main goal of this application is to obtain preclinical
data to evaluate the ability NR to improve the quality of life and function of Veterans with cancer as well as
cancer survivors who suffer the sequelae of chemotherapy. The proposed studies will focus on a platinum
compound, cisplatin, that is associated with a high incidence of painful peripheral neuropathy, as well as ocular
toxicity, and ototoxicity. The first aim of this proposal will determine whether prophylactic treatment with NR
prevents cisplatin-induced allodynia (hypersensitivity) to tactile and cool stimuli, as well as blunts the
aversive/affective dimension of the neuropathy. Hypersensitivity to tactile and cool stimuli will be assessed in
vehicle- and NR-treated rats by determining threshold to withdrawal from application of calibrated von Frey
filaments or a cool stimulus to the hind paw. The place escape avoidance paradigm will be used to assess
changes in the aversive/affective components of nociception. The second aim of the proposal will determine
whether prophylactic treatment with NR can prevent photophobia (light aversion), as well as corneal
hypersensitivity and deficits in tear production induced by cisplatin. Photophobia will be assessed in vehicle-
and NR-treated rats by measuring time spent in a brightly-lit chamber, while corneal hypersensitivity will be
assessed by changes in withdrawal responses to tactile stimulation of the cornea or degree of squinting
induced by application of hyperosmolar saline drops. Reflex and basal tear production will be assessed by
Schirmer's test. The final aim of this proposal will determine whether prophylactic treatment with NR can
prevent cisplatin-induced loss of hearing. Cochlear function will be assessed in vehic...

## Key facts

- **NIH application ID:** 10311115
- **Project number:** 5I21RX003464-02
- **Recipient organization:** IOWA CITY VA MEDICAL CENTER
- **Principal Investigator:** Marta Veronica Hamity
- **Activity code:** I21 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2020-09-01 → 2022-05-20

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10311115

## Citation

> US National Institutes of Health, RePORTER application 10311115, NICOTINAMIDE RIBOSIDE FOR THE TREATMENT OF CHEMOTHERAPY-INDUCED NEUROPATHY, DRY EYE SYNDROME, AND HEARING LOSS (5I21RX003464-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10311115. Licensed CC0.

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