# AVGN7, a Novel Gene Therapeutic for Treating Cancer Cachexia

> **NIH NIH R44** · AAVOGEN, INC. · 2021 · $134,809

## Abstract

PROJECT SUMMARY. The skeletal muscle wasting that occurs with cancer cachexia compromises
quality of life and is both directly and indirectly responsible for cancer mortalities. Tumor-derived and
tumor-responsive factors as well as many therapeutics themselves contribute to the cachectic state,
although nutritional support has little if any positive effect on restoring striated muscle mass or function.
Thus, novel tools for preventing muscle wasting in cancer patients could transform their treatment and
significantly improve their quality of life. Our research objective is to test a novel gene therapeutic for
enhancing muscle regeneration in a mouse model of tumor- and chemotherapy-induced cachexia and in
addition, to complete the GLP/toxicology studies required for IND filing. We hypothesize that attenuating
the intracellular signaling pathways responsible for muscle atrophy and impaired muscle regeneration will
in turn restore muscle mass and function and significantly delay mortality. In fact, Phase I-equivalent
data indicate that attenuating ActRIIB and Smad2/3 signaling with rAAV6:Smad7 (a.k.a. AVGN7)
significantly enhances muscle mass and function in wild-type mice and can completely prevent muscle
atrophy in different mouse models of cancer cachexia. Most importantly, this therapeutic does not
produce the serious off-target effects that have compromised development of competing technologies
that have either been shown to compromise blood vessel integrity or to possess this potential. Our
specific aims are to (i) test the hypothesis that rAAV6:Smad7 can prevent cancer- and chemotherapy-
induced muscle wasting, (ii) test the hypothesis that rAAV6:Smad7 reduces cancer mortality and (iii)
complete murine and non-human primate toxicology studies with rAAV6:Smad7. The proposed
approach is truly innovative as it utilizes a novel gene therapeutic and state-of-the art tools to
comprehensively assess muscle function at different scales. These studies are also highly significant as
they will provide a better mechanistic understanding of how tumor- and chemotherapy-induced muscle
wasting are independently affected by ActRIIB and Smad2/3 signaling. Most importantly, these
translational studies have the very real potential to impact clinical medicine and to advance clinical trials
of rAAV6:Smad7.

## Key facts

- **NIH application ID:** 10011562
- **Project number:** 5R44CA221539-04
- **Recipient organization:** AAVOGEN, INC.
- **Principal Investigator:** Buel Rodgers
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $134,809
- **Award type:** 5
- **Project period:** 2017-09-25 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10011562

## Citation

> US National Institutes of Health, RePORTER application 10011562, AVGN7, a Novel Gene Therapeutic for Treating Cancer Cachexia (5R44CA221539-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10011562. Licensed CC0.

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