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Cornell University

2017-2018

Unraveling the mechanism of action of orally administered F. prausnitzii to mitigate the emergence of antimicrobial resistance in food animals and improve animal health and productivity

The proposed work will evaluate a novel strategy that has the potential to be a superior alternative to antibiotic use, and will ultimately result in reduced antimicrobial resistance, and improved health and productivity of calves. Antibiotic resistance has become a major clinical and public health concern worldwide. We have identified and isolated Faecalibacterium prausnitzii (FP) from fecal samples of healthy animals. Moreover, we conducted in vivo studies and demonstrated the beneficial effects of administration of FP on calf health and growth. The goal of our work is to demonstrate that FP will be an efficacious and better alternative to the antimicrobials currently used in agriculture, firstly by helping to mitigate the emergence of antimicrobial resistance in food animals and its consequent spread to humans, and second by improving animal health and productivity. We postulate that these beneficial effects on productivity are due to increased insulin sensitivity induced by a systemic anti-inflammatory response. Thus, the proposed experimental design will allow for evaluation of applied and mechanistic aspects of the use of FP. Lastly, we hypothesize that FP treatment will significantly lower the presence of antibiotic-resistance genes in the fecal microbiome of calves treated with FP compared with calves treated with Medicated Milk Replacer.

Industry partner: Bactana Animal Health, LLC

Academic PI: Rodrigo Bicalho, College of Veterinary Medicine, Department of Population Medicine and Diagnostic Sciences

Folate.Scan – A comprehensive point-of-care diagnostic for folate status in women of childbearing age

Folate deficiencies in pregnant women are recognized as a cause of neural tube birth defects, including spina bifida and anencephaly, which occur during early stages of pregnancy, often before a woman knows she is pregnant. Fifty to seventy percent of these defects are preventable if recommended levels of folic acid are consumed before conception and through the first trimester of pregnancy. Our goal in this effort to prevent folate deficiencies is to develop Folate.Scan, a rapid point-of-care assay for diagnosing folate deficiency, which we plan to integrate with our existing NutriPhone platform. We believe that development of this test will reduce misdiagnosis of nutritional deficiencies leading to anemia, and inform treatment and broader public health interventions. We envision near term commercial success of the folate test itself as a stand-alone diagnostic for deficiencies in women of childbearing age and as part of the larger anemia suite of tests. VitaScan, our partner company has significant experience in the development of nutritional diagnostic tests.

Industry partner: VitaScan

Academic PIs:

  • David Erickson, Sibley School of Mechanical and Aerospace Engineering
  • Julia Finkelstein, Division of Nutritional Sciences

Process development for biomimetic boundary lubricants to treat osteoarthritis

Osteoarthritis (OA) affects more than 40 million Americans, accounting for up to 1 million hospitalizations each year. The disease also dramatically increases the risk of death, as well as causes about 500 deaths each year. Taking into account direct healthcare costs and indirect costs due to lost productivity and decreased quality of life, OA has an annual economic burden of more than $180 billion. OA patients have reduced amounts of lubricin – the slick, mucinous materials that, in healthy joints, is normally found on the surface of joint cartilage to lubricate the body’s heavier, slower movements. To meet this need, Dynamic Boundaries, Inc. and Cornell researchers developed, studied, and identified Biomimetic Boundary Lubricants (BBL) as potential revolutionary treatments that may slow or halt the progression of OA. The BBL are synthetic lubricins that restore natural lubrication of the knee, thus slowing disease progression similar to native lubricin. Additionally, the BBL have significant manufacturing advantages over native lubricin, which is currently being produced through more complicated and expensive methods.

Industry partner: Dynamic Boundaries, Inc.

Academic PI: Brett Fors, Chemistry and Chemical Biology

Performance evaluation of an on-farm qPCR-diagnostic test to detect mastitis pathogens in dairy cows

Mastitis is a major health concern on dairy farms and causes substantial economic losses for the industry in New York State and worldwide. Pathogen-based management decisions are most economical and crucial to avoid unnecessary use of antibiotics. The faster the infectious organism can be identified, the sooner the appropriate management protocol can be applied, reducing financial losses for the farmer. At present pathogens are commonly detected by aerobic culture of milk samples, requiring at least 24 to 48h to obtain results. Partnering with Acumen Detection, LLC, we previously developed an on-farm applicable, quantitative real time PCR assay to detect pathogens in milk. Requiring only minimal sample preparation, the assay can detect a panel of the most relevant pathogens within 3 to 5 hours. The system is designed to first identify presence or absence of a pathogen and then the organism at genus and/or species level. Farmers will be able to quickly decide whether treatment is indicated. Our present goal is to define sensitivity and specificity of the pathogen specific assays in a high throughput screening using milk samples with confirmed results from Quality Milk Production Services (QMPS). Furthermore we plan to evaluate the on-farm performance of the previously developed assay platform AcuPolaris™ in a field study on 3 commercial dairy farms in NYS including usability and effect on mastitis management decisions. The evaluated product will be ready to enter the market and provide farmers with a cost effective diagnostic test to identify mastitis pathogens in a timely manner.

Industry Partner: Acumen Detection LLC

Academics PIs:

  • Daryl Nydam, Population Medicine and Diagnostic Sciences, College of Veterinary Medicine
  • Anja Sipka, Population Medicine and Diagnostic Sciences, College of Veterinary Medicine

Bone-binding polymers to relieve bone-on-bone articulation pain in severe osteoarthritis

The goal of the proposed research is to develop and ultimately commercialize injectable bone-binding polymers capable of lubricating exposed bone in severe osteoarthritis.  Based on the initial successes of the collaborators, including the founding of Articulate Biomedical, LLC, (initially funded through the CAT program and entering clinical efficacy trials for moderate osteoarthritis in canines), we will synthesize a series of bone-binding polymers that form a lubricating coating on exposed bone in arthritic joints. The clinical goal is to decrease pain in severe osteoarthritis patients through mechanical, not pharmacologic, means thereby minimizing NSAID, COX-2 inhibitor, corticosteroid and opiate use.  Intra-articular hyaluronic acid injections do not relieve pain in severe osteoarthritis. The commercial goal is to establish a new Class III medical device to reduce severe osteoarthritis pain and improve the quality-of-life for patients who are either awaiting total joint replacement, are not surgical candidates, or who choose to opt against surgical intervention.

Industry partner: Articulate Biomedical, LLC

Adacemic PIs:

  • David Putnam, Chemical and Biomolecular Engineering/Biomedical Engineering
  • Larry Bonassar, Mechanical and Aerospace Engineering/Biomedical Engineering

Autonomous tissue cartridges for regenerative medicine and diagnostic screening

Open deep tissue wounds affect 6.5 million Americans at an annual cost of $25 billion dollars. Despite best reconstructive practice, these often result in permanent damage, disfigurement, and potentially death. Current methods of treatment are insufficient due to tissue replacements being too thin and having no embedded vascular network. Tissue with adequate vascular supply is the most crucial factor to successful grafting. Partnering with CorSolutions, LLC, we will develop an Autonomous Tissue Cartridge (ATC), a self-contained, miniature tissue culture platform for regenerative medicine and diagnostic screening. This system will provide closed-loop, high precision fluid control, connectors, and other features all integrated within a single 6-inch by 6-inch by 5-inch box. The system will be used to grow pre-vascularized tissue constructs for surgical implantation in regenerative medicine using patient derived adipose tissue cells, and serve as a biomimetic tissue platform for high throughput drug screening and toxicology studies.

Industry partner: CorSolutions, LLC.

Academic PI: Jason Spector, Weill Cornell Medical, Surgery Department, Division of Plastic & Reconstructive Surger