# Measuring cellular senescence to predict and prevent peripheral neuropathy

> **NIH NIH R44** · SAPERE BIO, INC. · 2021 · $914,673

## Abstract

ABSTRACT
Peripheral neuropathy is a debilitating pain syndrome that is prevalent in older patients and that can severely
impact patients’ quality of life, increasing their risk of falls, opioid usage, and healthcare costs. It can be incited
by neurotoxic drugs, chronic age-related conditions such as diabetes and kidney failure, and trauma, among
other etiologies. Current therapies to treat peripheral neuropathy are largely ineffective, thereby rendering
prevention particularly important. However, there are currently no good methods to identify patients at high risk
of developing neuropathy, as risk factors beyond the inciting agents are poorly understood. Aging as a risk factor
appears central to neuropathy progression; however, clinical data regarding the contribution of aging are
conflicting, possibly due to the heterogeneity of the aging process. Thus, there is a high unmet need to
understand risk factors associated with peripheral neuropathy, including whether and how disease-agnostic
mechanisms of aging such as senescence reflect individual vulnerability. Cellular senescence, has been
implicated in the etiology of common neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and multiple
sclerosis, and more recently cisplatin-induced peripheral neuropathy.
To understand risk factor of peripheral neuropathy, aside from inciting factors, and lay the groundwork for
applications across causes of peripheral neuropathy, initial studies must be conducted in a population that does
not have neuropathy at baseline, develops it with treatment, and experiences chronic, ongoing peripheral
neuropathy. Therefore, CIPN is an optimal first indication for both risk stratification and actionability.
Understanding the risk of CIPN is particularly important in breast cancer given (a) cancer prevalence and the
high incidence of CIPN, (b) common use of neurotoxic taxanes in nearly all chemotherapy regimens, (c) choice
of multiple regimens with similar efficacy but different CIPN risks, and (d) long survivorship requiring ongoing
management of CIPN which often persists for years after chemotherapy. Only through understanding a patient’s
individual CIPN risk can clinicians make informed decisions about which chemotherapy regimen will best
maximize efficacy and minimize CIPN risk for that person, thus offering more precise, personalized medicine in
the clinic.
Our data in a prospective study of patient with early stage breast cancer who received taxanes-containing
chemotherapy demonstrate that expression of cellular senescence biomarker, p16 correlated with acute CIPN.
In this Direct to Phase 2 proposal, we propose to build on our pilot data to create the first clinically validated
model for predicting CIPN risk and to identify patients who are at risk for developing acute CIPN as well as
patients whose symptoms may not resolve after chemotherapy completion (chronic CIPN).
With the aims of this proposal completed, we will be ready to design and execute a clinic...

## Key facts

- **NIH application ID:** 10324366
- **Project number:** 1R44AG072994-01A1
- **Recipient organization:** SAPERE BIO, INC.
- **Principal Investigator:** Natalia Mitin
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $914,673
- **Award type:** 1
- **Project period:** 2021-09-15 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10324366

## Citation

> US National Institutes of Health, RePORTER application 10324366, Measuring cellular senescence to predict and prevent peripheral neuropathy (1R44AG072994-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10324366. Licensed CC0.

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