AVGN a Novel Gene Therapeutic for Treating Cancer Cachexia

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R44CA221539-01
Agency Tracking Number: R44CA221539
Amount: $1,206,955.00
Phase: Phase II
Program: SBIR
Awards Year: 2017
Solicitation Year: 2014
Solicitation Topic Code: 102
Solicitation Number: PAR14-088
Small Business Information
13420 GLEN LEA WAY, Rockville, MD, 20850-3638
DUNS: 079995027
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 (208) 596-9807
Business Contact
Phone: (208) 596-9807
Email: danrodgers@aavogen.com
Research Institution
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 Smad signaling with rAAV Smad a k a AVGN 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 rAAV Smad can prevent cancer and chemotherapy induced muscle wasting ii test the hypothesis that rAAV Smad reduces cancer mortality and iii complete murine and non human primate toxicology studies with rAAV Smad 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 Smad signaling Most importantly these translational studies have the very real potential to impact clinical medicine and to advance clinical trials of rAAV Smad RELEVANCE TO PUBLIC HEALTH The striated muscle wasting that occurs with cancer cachexia compromises quality of life and is both directly and indirectly responsible for cancer mortalities The proposed studies will develop a novel gene therapy for preventing this wasting whether it results from tumor burden or chemotherapy These studies will also advance the gene therapy towards clinical trials by completing the required toxicology studies

* Information listed above is at the time of submission. *

Agency Micro-sites

SBA logo
Department of Agriculture logo
Department of Commerce logo
Department of Defense logo
Department of Education logo
Department of Energy logo
Department of Health and Human Services logo
Department of Homeland Security logo
Department of Transportation logo
Environmental Protection Agency logo
National Aeronautics and Space Administration logo
National Science Foundation logo
US Flag An Official Website of the United States Government