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Ithaca, NY, United States

Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 150.00K | Year: 2013

DESCRIPTION (provided by applicant): Agave BioSystems and Professor Makoto Kuro-o at the University of Texas Southwestern Medical Center are proposing a collaborative effort to screen for novel small molecules acting as agonists or antagonists of the Klotho and Klotho- dependent endocrine Fibroblast Growth Factors. The expected outcome of this Phase I effort will be the validation of a high-throughput screening methodology and the identification of confirmed hits which modulate the activity of endocrine Fibroblast Growth Factors FGF21 and FGF23. The effect of each hit will be confirmed in FGF- specific cell-based assays verifying changes in known activities of the Fibroblast Growth Factors. The small scale proof of concept screening campaign of the Phase Iwill be followed by a larger campaign in the Phase II do identify series of novel agonists and antagonists offering to uncover a broader set of structures and mechanisms of action for this novel effectors of endocrine Fibroblast Growth Factors. Selected hits will undergo early hit-to-lead optimization and be evaluated for cytotoxicity prior t small animal testing. Rodent disease models will be treated and the expected molecular, cellular and physiological changes of endocrine FGF activity modulation will be verified. This translational research project for therapeutic target validation will lead to the development of potential new drugs against chronic kidney disease, diabetes, obesity and cancer. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE:Agave BioSystems and Professor Makoto Kuro-o at the University of Texas Southwestern Medical Center are proposing a collaborative effort to screen for novel small molecules acting as antagonists of the Klotho-dependent endocrine Fibroblast Growth Factor FGF23 and as agonists of the Klotho-dependent FGF21. The identification of such compounds will be used for therapeutic target validation and potentially lead to the development of novel drugs against chronic kidney disease, diabetes, obesity and aging.

Agency: Department of Defense | Branch: Office for Chemical and Biological Defense | Program: SBIR | Phase: Phase II | Award Amount: 750.00K | Year: 2011

Organophosphorus chemical warfare nerve agents (OP-CWA) are attractive to terrorist groups and rogue states as an inexpensive and accessible technology for chemical warfare. OP-CWA and organophosphate pesticides cause severe neurological symptoms and death by inhibiting the enzyme acetylcholinesterase (AChE); the resulting excess acetylcholine accumulates and overstimulates the human or animal body. Other esterases and organophosphatases in the blood either bind (butyrylcholinesterase, BChE) or catalytically degrade (paraoxonase, PON1) OP-CWA. Therefore, it is critically important to be able to quickly monitor the human blood complement of OP-CWA enzymes to assess both susceptibility and current condition. For military and civilian clinical use, a high-throughput, minimally invasive assay system is needed to quickly and accurately screen large numbers of soldiers/agricultural workers/first responders for OP-CWA or OP-pesticide exposure. The currently available WRAIR assay is high-throughput, uses a minimal amount of whole blood, and is sensitive and accurate for AChE and BChE levels. An assay that additionally measures PON1 and albumin esterase activities relevant to OP degradation and/or binding is greatly needed to more fully assess OP-CWA or -pesticide susceptibility for individuals at risk.

Agency: Department of Defense | Branch: Army | Program: SBIR | Phase: Phase II | Award Amount: 780.00K | Year: 2012

Field testing of water samples is needed for broad and sensitive detection of toxic industrial chemicals, or TICs. The use of unicellular organisms in cell-based detection systems is particularly advantageous both because these organisms have developed a natural ability to respond to environmental changes, and because several methods for long-term storage with minimal maintenance requirements have been established and tested. Long-term storage of packaged freeze-dried cells with no need for significant environmental controls such as temperature eliminates limitations in the development of a rugged field-deployable device perfectly adapted to logistical requirements in a military setting. The need for a toxicant of interest to cross the natural barriers such as cell walls or membranes is perhaps the only significant limitation to the detection capability of any cell-based system. This will be addressed as part of the proposed effort by testing known genetic and biochemical approaches to the permeabilization of the bacterial cell wall to develop novel biosensors with broader and more sensitive detection capabilities. The Phase I established proof-of-concept for this novel biosensor. In the Phase II, a complete prototype will be developed ready for field testing.

Agency: Department of Defense | Branch: Air Force | Program: STTR | Phase: Phase II | Award Amount: 711.62K | Year: 2014

ABSTRACT: Protection of first responders who are exposed to hazards including chemical warfare agents (CWAs) is a very critical need. The need is derived from not only their welfare but their ability to respond, protect the community and provide logistical support to the response. A simple exposure monitor would provide critical information to the first responder and allow them to respond accordingly and to also help to monitor the environment. Exposure monitoring would also provide a more realistic picture of the threat with multiple points of sampling. Therefore, it would be useful to develop systems that could harness the body"s own chemistry to help detect the presence of CWA exposure in the field. CWAs are toxic because of their direct and indirect impact on biological processes in the human body. Agave BioSystems, in collaboration with Dr. Carl Batt of Cornell University are exploring nanoscale materials specifically tailored to create a new class of highly sensitive, robust and personal platform to determine military personnel exposure to OP CWAs. Agave BioSystems has demonstrated that the dye impregnated NPs are responsive to CWA simulants in a cellular environment. During the Phase II program, improved dye impregnated NPs and a prototype NP detector will be developed. The fluorogenic NPs will be incorporated into tattoos to create an in vivo biosensor capable of rapid detection of OP CWA exposure. BENEFIT: The possibility of CWA troop exposure to CWA agents is of major concern to the US military. A variety of systems exist to detect the presence of CWA agents in non-biological settings, but the exposure of humans to these agents can often go undetected until symptoms begin to appear. The development of a simple, biologically based system for detecting either acute or chronic CWA exposure would be of significant benefit to deployed military troops. In this STTR Phase II program, Agave BioSystems, in collaboration with Dr. Carl Batt of Cornell University, propose to develop a fluorogenic nanoparticle sensor that can be imbedded into the dermal layer of military personnel as a tattoo. This tattoo would have the unique characteristic of becoming fluorescent upon exposure to low levels of organophosphate CWAs. A small, hand-held optical sensor would then be used to record changes in fluorescence emitted from the tattoo, rapidly indicating exposure to potential CWAs. In addition to military personnel, civilian first responders are also at risk of exposure to organophosphate agents, either as CWAs dispersed by terrorists or as insecticides present in high concentrations at agricultural and industrial sites. First responders can include police, fire, and EMS personnel, as well as search and rescue, and National Guard troop. While the exact number of first responders in the US is not known, some estimate that there may be as many 10 million people who could be characterized as first responders. According to the Bureau of Labor Statistics, there were over 1.3 million professional and volunteer fire personnel, about 800,000 police, and about 250,000 EMTs and paramedics in the US alone. While it may not be necessary to use an implantable tattoo biosensor for detecting OP exposure in every first responder, the market for tattoos and fluorescence monitors for US military and National Guard troops, as well as police, fire and EMS personnel could be well over 1 million individuals. If even a small fraction (1%) of this number requires monitoring, the market for fluorescent biosensor tattoos and handheld monitors could exceed $10 million. In addition to the detection of OP CWAs and pesticides, implantable biosensors such as those described in this proposal, adaptation of this technology could readily yield biosensors capable of detecting a wide range of chemical contaminants, such as volatile organic compounds (VOCs) and toxic industrial chemicals (TICs). Potential diagnostic markets for VOC and related compound detection include homeland security, law enforcement and the military. The chemical modularity of the approach described herein should ably address the need for real time, field deployable sensors potentially capable of detecting myriad families of chemical toxicants in a multitude of settings. Upon completion of the Phase II program, Agave BioSystems will develop a detailed Phase III plan for the commercialization of the resulting technology.

Agency: Department of Defense | Branch: Defense Advanced Research Projects Agency | Program: SBIR | Phase: Phase II | Award Amount: 1.00M | Year: 2013

Wound management becomes increasingly challenging due to bacterial infections, especially from epidemic drug-resistant strains. To address this problem, Agave BioSystems proposes to develop a RANT (Rapidly Adaptable Nanotherapeutics) breadboard system built upon the modules successfully established in Phase I of this work. The proposed breadboard system will use genomic sequencing data generated from wound pathogens to identify unknown pathogens and gene targets. These targets will serve as the basis for design of antisense PNA sequences to be incorporated into a PNA-CPP modified DNA nanoparticle. The pathogen-specific, ad hoc-developed nanoparticles are anticipated to possess characteristics of high efficacy, stability and penetration abilities to facilitate effective and specific elimination of emerging drug resistant microbes.

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