# Selective actin remodeling of sensory neurons for acute pain management

> **NIH NIH R43** · NEUROCARRUS, INC. · 2020 · $245,417

## Abstract

PROJECT SUMMARY
There is an urgent need for new approaches to treat acute human pain without the risk of Substance Use
Disorders (SUDs). The most effective approved pain pharmaceuticals, including narcotics and anesthetics,
are not neuron-specific and consequently suffer from off-target effects like addiction, inhibition of motor
neurons, and destruction of the surrounding tissues. When inflammation occurs, actin polymerization occurs
in sensory neurons, leading to the sensitization of purinergic receptors and abnormal pain behaviors.
Targeted actin remodeling could be an effective approach to reduce acute nociceptive pain, but there are no
small-molecule inhibitors with adequate specificity for sensory neurons that correctly modulate the
cytoskeleton. Neurocarrus proposes a new therapeutic approach for nociceptive pain based on an innovative
engineered protein called N-001 that selectively targets sensory neurons and acts only at an intra-cellular
level inducing limited and reversible depolymerization of the axon-associated actin cytoskeleton. This
innovative biologic drug will provide specificity towards sensory neurons while leveraging the features of the
peripheral nervous system to eliminate pain locally without interacting with the central nervous system. In
vivo, N-001 administration by subcutaneous injection prevents acute pain in rodent models at lower doses
and with a longer duration than standard opiates. Further advancement of N-001 as a therapeutic candidate
for nociceptive pain requires demonstration of the feasibility of using N-001 as a product for human pain
management. In this Phase I SBIR project, Neurocarrus will evaluate the response of mice to post-operative
pain after treatment with N-001. The selective neuron targeting ability of N-001 will be validated by generating
in vivo histologic data supporting its mechanism of action. The identification of nociceptor subtypes that are
sensitive to actin depolymerization and the ability to selectively silence them would establish specific metrics
for the use of N-001 as a pain therapeutic. Finally, a demonstration of acceptable drug pharmacology will be
performed to de-risk future IND-enabling studies in Phase II.

## Key facts

- **NIH application ID:** 10138638
- **Project number:** 1R43NS120337-01
- **Recipient organization:** NEUROCARRUS, INC.
- **Principal Investigator:** Paul Blum
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $245,417
- **Award type:** 1
- **Project period:** 2020-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10138638

## Citation

> US National Institutes of Health, RePORTER application 10138638, Selective actin remodeling of sensory neurons for acute pain management (1R43NS120337-01). Retrieved via AI Analytics 2026-06-15 from https://api.ai-analytics.org/grant/nih/10138638. Licensed CC0.

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