TS-002176 — In order to effectively treat bacterial infections, a clear understanding of the bacterium’s antibiotic sensitivity is needed. Researchers at Nationwide Children’s Hospital’s Center for Microbial Pathogenesis created a new method to assist in prescribing antibiotics for infections caused by a biofilm to reduce the dosage and the length of antibiotic treatments.

TS-002168 — Children have a higher chance of morbidity and mortality from respiratory viral infections. Severe respiratory viral infections like Respiratory Syncytial Virus (RSV) and Parainfluenza viruses can lead to the development of asthma in patients. Clinical researchers at Nationwide Children’s Hospital found that neuregulin-1 (Nrg-1) may be an effective and protective treatment for patients diagnosed with severe respiratory viral infections. Their successful models with mice showed that Nrg-1 may prevent post-viral airway disease and reduce mortality if further studied and applied to human patients in the future.

TS-001034 — Salmonella is often caused by contact with animals that carry bacteria, contaminated food, or water. It has been observed that children are commonly afflicted by salmonella, and typically treatment includes fluids, medical care, and sometimes pharmaceuticals. A team of researchers at Nationwide Children’s hospital have identified a lead compound that includes a biofilm with anti-salmonella characteristics and acts as an inhibitor. Use of this compound with the antibiotic ciprofloxacin improves the elimination of bacterial infection in at-risk organs such as the liver and spleen.

TS-001029 — A major complication associated with breast implant prostheses is the occurrence of capsular contracture, occurring in 20%-25% of patients. Severe forms of capsular contracture constitute failure of the reconstruction with significant implications for increased cost owing to an increased need for recurrent medical interventions, as well diminished quality of life for patients. Capsular contracture occurs as the result of the patient’s immunologic ‘foreign body’ response to the implant material. The inventors’ vision is to develop a technology whereby the active metabolites of Tamoxifen (endoxifen) are conjugated to implant biomaterial in a manner allowing for localized delivery of endoxifen. They anticipate that local delivery of endoxifen will successfully reduce capsule formation around implant material by reducing the immunologic foreign body response. This is a technology that could be licensed to implant manufacturers (breast, implantable cardiac devices, etc.) Technology Overview: Breast augmentation and reconstruction is a common practice, especially in those afflicted by breast cancer. One of the most common issues that comes with this process is the formation of capsular contracture. This is a direct result of the patient’s immunologic ‘foreign body’ response to the implant material, which can impact the need for significant medical interventions and diminished quality of life. The current pharmacologic treatment for breast cancer is the chemical compound known as Tamoxifen, which acts as a chemo-preventative medication for hormone sensitive breast cancers. A team of researchers at Nationwide Children’s Hospital and Ohio State University aims to localize the delivery of tamoxifen to significantly reduce the immunologic foreign body response around implant material for use in both cancer-based breast reconstruction and cosmetic procedures Benefits: No pharmacotherapeutics currently exist to address capsular contracture and no biomaterial advances have been made to specifically reduce the foreign body response to breast implants Stage of Development: Mouse studies are currently underway using systemic delivery of Tamoxifen for treatment of capsular contracture in breast implants. A manuscript is in preparation. Future mouse studies will focus on local delivery of endoxifen for treatment of capsular contracture in breast implants; then look at other implant types and different coating types. Potential Applications / Markets: According to the report published by Allied Market Research, the medical implant industry estimated $85.38 billion in 2019, and is estimated to generate $147.46 billion by 2027, manifesting a CAGR of 7.2% from 2020 to 2027. According to a report published by Fortune Business Insights, the breast implant market was worth $2.76 billion in 2019 and is projected to reach $3.05 billion by the end of 2027, exhibiting a CAGR of 7.2% during the forecast period, 2020-2027. Opportunity / Seeking: -Licensing IP Status: Patent application submitted

TS-000610 — Hemorrhagic shock and resuscitation (HS/R)-induced injuries often result from trauma or severe blood loss and can quickly progress to organ failure. Researchers at Nationwide Children’s Hospital have developed a novel method for treating subjects at risk for HS/R by administering Heparin Binding-Epidermal Growth Factor (HB-EGF). Administration of HB-EGF protects intestinal epithelial and endothelial cells from HS/R-induced injury in a rat model. This novel method may have broad clinical availability for treating or preventing a range of intestinal injuries in pediatric and adult patients.

TS-000499 — Intrabacterial pathogens are infectious bacteria that infiltrate cells and infect those that come in contact with them. Significant bacterial infections include those of salmonella, often caused by the consumption of contaminated food, and francisella, caused by handling infected animal tissue. A team at Nationwide Children’s Hospital has developed novel therapeutics to inhibit the growth of these bacteria in infected cells, designated as KH-1 and KH-2. These compounds target the host immune pathway to help the infected cell control bacterial growth, and control infections in not only antibiotic susceptible strains, but also multidrug resistance strains. Benefits: The proposed application of the compound is a novel method to control infections by intracellular pathogens. Traditional antimicrobials directly target bacteria and frequently select for antibiotic resistant mutants. Our preliminary data indicate that KH-1 does not directly kill bacteria, rather it targets the host immune pathway to help the infected cell control bacterial growth. The KH-1 is proposed for controlling infections by not only antibiotic susceptible strains but also multidrug resistance strains. Stage of Development: The use of antimicrobials to treat infections selects for antibiotic resistant mutants. Antibiotic resistance is a top threat to public's health. In the U.S alone, antibiotic resistance is responsible for more than 2 million infections and 23,000 deaths per year (CDC 2019). Novel intervention strategy is urgently needed to combat multidrug resistant strains and replace the use of antibiotics. Prototype: Intracellular pathogens use multiple mechanisms to manipulate the host cell immunity in such a way that is favorable for pathogens to grow and ultimately cause host cell death that is indicated by releasing some intracellular components from the infected host cells including lactate dehydrogenase. Host targeted-drugs protect the infected cell from death can be used as host therapy to control infections-it allows the infected host cell time to kill the ingested microbe. We screened a kinase inhibitor library for compounds that limit cell death from Salmonella infection and identified KH-1 as anti­Salmonella, and in subsequent testing, also anti-Francisella. Proof of principle: KH-1 treatment reduces host cell lysis and intracellular bacterial (Salmonella and Francisella) growth inside J774.1 macrophages. KH-1 also protects the mice from lethal Salmonella and Francisella infection. Future Work: 1- We will identify KH-1 target(s) in the host cell and investigate how KH-1 helps the infected cell to limit bacterial growth. 2- We will study any observed side effects of KH-1 to the host. 3- We will study pharmacokinetics and dynamics of KH-1. 4- We will improve KH-1 delivery to achieve the best effects. 5- We will examine the effects of KH-1 on controlling multi-drug resistant intracellular bacterial strains. Potential Applications / Potential Markets: 1- Treating infection caused by intracellular pathogens not limiting to Salmonella and Francisella. 2- Treating infections caused by multidrug resistant intracellular pathogens. Opportunity/Seeking: Commercial Partner Licensing IP Status: Patent Application Submitted Provisional Patent

TS-000480 — Intrabacterial pathogens are infectious bacteria that infiltrate cells and infect those that come in contact with them. Significant bacterial infections include those of salmonella, often caused by the consumption of contaminated food, and francisella, caused by handling infected animal tissue. A team at Nationwide Children’s Hospital has developed novel therapeutics to inhibit the growth of these bacteria in infected cells, designated as KH-1 and KH-2. These compounds target the host immune pathway to help the infected cell control bacterial growth, and control infections in not only antibiotic susceptible strains, but also multidrug resistance strains. Benefits: The proposed application of the compound is a novel method to control infections by intracellular pathogens. Traditional antimicrobials directly target bacteria and frequently select for antibiotic resistant mutants. Our preliminary data indicate that KH-1 does not directly kill bacteria, rather it targets the host immune pathway to help the infected cell control bacterial growth. The KH-1 is proposed for controlling infections by not only antibiotic susceptible strains but also multidrug resistance strains. Stage of Development: The use of antimicrobials to treat infections selects for antibiotic resistant mutants. Antibiotic resistance is a top threat to public's health. In the U.S alone, antibiotic resistance is responsible for more than 2 million infections and 23,000 deaths per year (CDC 2019). Novel intervention strategy is urgently needed to combat multidrug resistant strains and replace the use of antibiotics. Prototype: Intracellular pathogens use multiple mechanisms to manipulate the host cell immunity in such a way that is favorable for pathogens to grow and ultimately cause host cell death that is indicated by releasing some intracellular components from the infected host cells including lactate dehydrogenase. Host targeted-drugs protect the infected cell from death can be used as host therapy to control infections-it allows the infected host cell time to kill the ingested microbe. We screened a kinase inhibitor library for compounds that limit cell death from Salmonella infection and identified KH-1 as anti­Salmonella, and in subsequent testing, also anti-Francisella. Proof of principle: KH-1 treatment reduces host cell lysis and intracellular bacterial (Salmonella and Francisella) growth inside J774.1 macrophages. KH-1 also protects the mice from lethal Salmonella and Francisella infection. Future Work: 1- We will identify KH-1 target(s) in the host cell and investigate how KH-1 helps the infected cell to limit bacterial growth. 2- We will study any observed side effects of KH-1 to the host. 3- We will study pharmacokinetics and dynamics of KH-1. 4- We will improve KH-1 delivery to achieve the best effects. 5- We will examine the effects of KH-1 on controlling multi-drug resistant intracellular bacterial strains. Potential Applications / Potential Markets: 1- Treating infection caused by intracellular pathogens not limiting to Salmonella and Francisella. 2- Treating infections caused by multidrug resistant intracellular pathogens. Opportunity/Seeking: Commercial Partner Licensing IP Status: Patent Application Submitted

TS-000241 — AR-12 to treat Neisseria gonorrhoeae infection of the normal human mucosa

TS-000235 — Dental caries, or tooth decay, affects 84% of adults and is caused by the demineralization of the tooth surface by bacteria (Streptococcus mutans and other Streptococcal species) residing in the oral cavity. These bacteria possess surface-associated glucosyltransferases, which convert sucrose to glucan, thus facilitating their attachment to the tooth surface and further colonization. Current treatments for the prevention of tooth decay involve flooding the oral cavity with oral health care products which harm both healthy (commensal) and pathogenic (harmful) bacteria. Investigators at Nationwide Children’s Hospital have developed a novel anti-cariogenic formulation that provides targeted elimination of cariogenic and harmful bacteria with minimal disturbance of commensals.

TS-000205 — Otitis media (OM) is a leading cause of hearing loss in children in the U.S. Nontypeable Haemophilus influenzae (NTHI) is a major causative agent of OM and other diseases of the respiratory tract. NTHI-mediated OM often persists despite repeated antibiotic therapies, due in part to the ability of NTHI to invade host epithelial cells. Researchers at Nationwide Children’s Hospital have developed a novel approach to treating or preventing OM by inhibiting Arp2/3-mediated invasion of host cells.