# Peripheral Nerve-on-a-chip for Predictive Preclinical Pharmaceutical Testing

> **NIH NIH SB1** · AXOSIM, INC. · 2022 · $299,226

## Abstract

PROJECT SUMMARY
The drug development pipeline is plagued by unacceptable rates of attrition due in large part to toxicities that
are not identified in pre-clinical stages of development. While peripheral neuropathy remains a common toxic
side-effect of new drugs, such toxicity is typically only first identified during late-stage preclinical development or
even early clinical trials. Drug-induced neurotoxicity is caused by off-target effects of pharmaceuticals that lead
to sensory, motor, and cognitive deficits. While rarely fatal, drug-induced peripheral neurotoxicity can lead to
permanent nerve damage and in some cases can be a dose-limiting side effect, leading patients to reduce
dosage or stop treatment altogether. “Organ-on-a-chip” technologies are steadily becoming adopted by the
pharmaceutical industry because of their ability to help de-risk lead compounds during pre-clinical development.
Towards that end, we demonstrated the technical feasibility and successful commercial deployment of a
peripheral “nerve-on-a-chip,” consisting of a 3D neuronal/glial spheroid projecting dense axonal fiber tracts,
resembling peripheral nerve anatomy. Progress during the prior award phases strongly demonstrated the
feasibility of using microengineered neural tissues that are amenable to morphological and physiological
measurements analogous to those of clinical tests. The use of structural and functional analyses in vitro led to
drug-induced neural toxicity that manifested in ways analogous to clinical neuropathology. Valuable feedback
from industry early adopters has enabled us to revise previous assumptions and resolve many technical
challenges, and we now seek to deploy the technology at a commercial scale. The aims of this proposal are to
manufacture customer-ready multiwell devices with integrated microelectrodes, and to provide a more complete
biological characterization of our model using high-throughput transcriptomics. Completion of these aims will
position this technology for scalable implementation, enabling us to offer the platform widely to pharmaceutical
companies seeking information about peripheral neuropathy earlier in the preclinical drug development process
than currently possible.

## Key facts

- **NIH application ID:** 10492954
- **Project number:** 2SB1TR001270-04
- **Recipient organization:** AXOSIM, INC.
- **Principal Investigator:** Jabe L Curley
- **Activity code:** SB1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $299,226
- **Award type:** 2
- **Project period:** 2016-02-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10492954

## Citation

> US National Institutes of Health, RePORTER application 10492954, Peripheral Nerve-on-a-chip for Predictive Preclinical Pharmaceutical Testing (2SB1TR001270-04). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10492954. Licensed CC0.

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