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Aminoglycosides with reduced ototoxicity

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41AI126874-01
Agency Tracking Number: R41AI126874
Amount: $600,000.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NIAID
Solicitation Number: PA15-270
Solicitation Year: 2015
Award Year: 2016
Award Start Date (Proposal Award Date): 2016-08-01
Award End Date (Contract End Date): 2019-07-31
Small Business Information
900 B W FARIS RD, Greenville, SC, 29605-4255
DUNS: 831389122
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 (864) 656-1106
Business Contact
Phone: (864) 656-1106
Research Institution
CLEMSON, SC, 29634-0001
 Nonprofit college or university
PROJECT SUMMARY Aminoglycosides are one of the cheapest and well known antibiotics in clinical use for over years but one of the major limitations in their use is their ototoxicity We are developing fast and low cost methods to develop aminoglycosides with anti ribosomal activities and reduced toxicity In this project we will identify novel aminoglycoside antibacterials that show reduced ototoxicity Complexes between ribosomal components will be exploited as targets for small molecule drug libraries that inactivate the ribosome stopping bacterial protein synthesis and causing bacterial death while reducing toxicity This work addresses an important health issue antibiotic ototoxicity and presents creative steps towards a novel solution to this problem The work proposed here a multidisciplinary effort encompassing antibacterial screening and ototoxicity studies using zebrafish and guinea pig models describes the development of novel aminosugar rRNA binders as non toxic antibacterial therapeutics The success of the proposed work would be a significant addition to currently available approaches in antibacterial therapy We propose using a zebrafish assay to identify conjugates that show reduced toxicities opening possibilities for developing reduced toxicity RNA targeted aminosugar therapeutics PROJECT NARRATIVE The proposed project presents a strategy for developing novel aminoglycoside therapeutics with reduced ototoxicities with evasion of resistance Antimicrobial resistance occurs when microorganisms often infectious bacteria viruses and certain parasites are no longer sensitive to drugs that were previously used to treat them this is of global concern because it hampers our ability to control infectious disease and increases the costs of health care In order to combat this world wide problem innovative strategies for antibiotic drug design must be implemented The proposed research describes a strategy for improving the therapeutic index of aminoglycosides by designing novel structures that lower their ototoxicity and evade common resistance pathways

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

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