# Toward Precision Gene Therapy for Treatment of Severe Pain in Older Individuals

> **NIH NIH R33** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $501,000

## Abstract

Project Summary: The primary goal of this R21/R33 Translational Aging Research Identification award
is develop, optimize, and validate a novel gene therapy-based treatment approach for refractory pain in
older individuals. Pain is a major socioeconomic problem, affecting more than 25% of adults in the US.
The lack of effective treatments for pain has fueled the opioid epidemic. In elderly patients, treatment
options are even more limited, on account of medical conditions that prevent specific drug use as well
as increased risks of side effects due to polypharmacy. Evidence from human genetics and mouse
models suggests that reducing firing in primary pain-sensing neurons, nociceptors, is sufficient to
abrogate pain. We first design new mechanisms for delivering to AAVs specifically to nociceptors. We
then develop novel approaches to decrease nociceptor firing, and we validate this reduction using
whole cell patch clamp electrophysiology in both primary mouse nociceptors and nociceptors derived
from human induced pluripotent stem cells. We validate pain models in aged animals, and obtain proof-
of-concept efficacy for the AAV-based treatment strategy using the pain models in aged animals. The
successful completion of the project sets the stage for continued preclinical development of AAV-based
therapy for refractory pain in older individuals.

## Key facts

- **NIH application ID:** 11044366
- **Project number:** 4R33AG075419-03
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Brian Jason Wainger
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $501,000
- **Award type:** 4N
- **Project period:** 2022-02-01 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11044366

## Citation

> US National Institutes of Health, RePORTER application 11044366, Toward Precision Gene Therapy for Treatment of Severe Pain in Older Individuals (4R33AG075419-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11044366. Licensed CC0.

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