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-001229 — Mutations in the Myotonic Dystrophy Protein Kinase gene (DMPK) cause an autosomal dominant inherited disease referred to as Myotonic Dystrophy. Myotonic Dystrophy affects more than 1 in 8,000 people worldwide. Myotonic dystrophy results in progressive muscle weakness, stiffness and wasting. Currently, here are no treatments for this disease. A team of researchers at Nationwide Children’s Hospital have designed short hairpin constructs of AAV-shRNA which can be used to silence DMPK mRNA and therefore potentially treat myotonic dystrophy.

TS-001227 — A team of physicians at Nationwide Children's Hospital have developed a process to improve the acceptance of implanted vascular grafts. This Tissue Engineered Vascular Graft (TEVG) is patient-specific. It seeds patient cells onto a biodegradable tubilar scaffold, which is designed to dissolve with hydrolysis so that only the growing vessel remains. This system, the Closed Seeding System, combines patient imaging data, 3D-printing capabilities, and efficient collection and subsequent seeding of patient cells onto the TEVG scaffolding.

TS-001225 — Cystic fibrosis is an inherited disorder that affects cells that produce sweat and mucus, causing significant damage to the digestive system, lungs, and other organs. A team at Nationwide Children's Hospital has developed a non-invasive monitoring system to track and test a patient with this disease. This technology is a skin patch that measures the metabolomics of the patients sweat to evaluate the clinical health of patients afflicted with cystic fibrosis.

TS-001224 — Decks of cards have been used to facilitate knowledge for decades. A team of researchers led by Dr. Elise Berlan have developed a series of cards that combine summaries of contraceptive counciling information and patient preferences. This includes key components of contraceptive preferences which can then be used with a care provider to determine the best form of contraceptive for the patient's preference and decreases the stigma associated with discussing topics like contraceptives as adolecents or young adults.

TS-001178 — Currently there are few existing methods on coronary flow pattern automation. The DECFA platform fulfills this unmet need by predicting diseased coronary blood flow by integrating previously unutilized data features from (sonographic) Doppler echocardiography measurements, cardiac functional and other physiological data (e.g. heart rate, body weight, etc) using machine learning. The DECFA program is superior to manual intervention as it provides more efficient analysis, more accurately, and can accept raw video files of PW Doppler and Color Doppler B-mode files, applicable on mouse models, potentially applicable to humans. DECFA can analyze raw PW Doppler AND Color Doppler B-Mode AVI video files to calculate overall coronary blood flow and coronary flow reserve, and the separation of each coronary flow pattern into 4 distinct phases representative of the stages in a cardiac cycle. Benefits: More efficient analysis over manual intervention, less error than manual intervention, capable of accepting raw video files of PW Doppler and Color Doppler B-mode files, applicable on mouse models, potentially applicable to humans (not yet validated). New features include the analysis of raw PW Doppler AND Color Doppler B-Mode AVI video files to calculate overall coronary blood flow and coronary flow reserve, and the separation of each coronary flow pattern into distinct phases representative of the stages in a cardiac cycle. The machine learning aspect brings state-of-the-art technology to determine whether it may be useful in directly predicting/diagnosing coronary microvascular disease. Stage of Development: We are currently in the final stages of completing the data analysis for all of the in vivo coronary and cardiac physiological parameters that will be used to perform the final runs through the machine learning process. We did perform an “interim” analysis using about half of the data, the results of which were promising (inconclusive at this point, but they put the predictive value of coronary flow patterns above 90% for identifying diseased coronary blood flow). This process also uses the whole envelope instead of discrete points of the coronary flow pattern, in addition to the texture-analysis extension. After this process is complete in mice, we plan to obtain human coronary blood flow patterns to determine whether this could be clinically useful beyond research applications. Potential Applications/Markets: Our program could be utilized in a research setting for robust, comprehensive, and more efficient analysis of coronary flow patterns in mice measured through Doppler Echocardiography (It solves the problem of large inter/intra observer error and time required for manual analysis). The program could also be used clinically for use in the medical field for the same analysis if adjusted for human use. It could also be used as an add on feature to the VisualSonics Vevo 2100 software for added capabilities in analyzing PW Doppler coronary flow patterns and Color Doppler B-mode files. The parameters that we identify in our program could be potentially useful in clinical diagnostics/machine learning/prediction modeling for better identifying and predicting disease. Furthermore, we envision that this could be tested and applied to clinical coronary Doppler echocardiograms, with the readout being predictability of coronary microvascular disease based on the machine learning algorithm of coronary flow patterns. Opportunity/Seeking: Development Partner Commercial Partner Licensing IP Status: Know-how based Copyright

TS-001037 — When it comes to the safety of our children, innovation never stops. There have been many improvements to the safety of devices and receptacles that can be toxic or life threatening if consumed or exposed to skin. A team of researchers at Nationwide Children’s Hospital have incorporated this desire for security into a common household product: the spray bottle. Often filled with harmful chemicals, spray bottles remain one of the leading causes of chemical exposure injuries in children. The team at NCH has developed a “two-step authentication” spray nozzle that requires the dexterity beyond that of a small child. This dual trigger approach requires a full grip that prevents kids from accessing the contents of the spray bottle, while remaining easily usable by adults and seniors.

TS-001036 — School can be a daunting experience. Constant motion, public speaking and a new environment can increase anxiety in children, sometimes leading to school avoidance. A team at Nationwide Children’s Hospital has developed a solution, where exposure therapy procedures are combined with modern technology can improve the school experience for people of all ages. Using a Virtual Reality (VR) Simulation, clinicians are able to use the multi-user capability to interact with and guide their patient through new environments such as classrooms, hallways and lunchrooms, as well as scenarios known to trigger increased anxiety such as public speaking or asking for help. Biofeedback components help collect data so that the clinician can adapt the experience to the user. Although targeted for school-aged children, this technology can be modified to treat any person with school or public phobia.

TS-001035 — Shiny R is an open source platform that allows a framework to develop online applications. With minimal required background in coding principles, a team of researchers at Nationwide Children’s Hospital were able to display and interact with the analysis made of single-cell transcriptome. Shiny R generates visualizations that include UMAP plots and presents features of single-cell RNA and transcriptomic data without extensive training in R programming. Improvements made on this existing technology includes importing data, cell filtration, principle component analysis, clustering, dimensional reduction, merging datasets, and Graphical user interface (GUI)-based generations of gene expression plots. This significantly improves the visualization and analysis of single-cell transcriptome analysis.

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-001033 — Intravascular Ultrasound Images (IVUS) is a process that uses micro technology to provide images of blood vessels, their inner walls (endothelium) and the inside of veins. The analysis of these images allows clinicians to analyze luminal and scaffold boundaries, identify the presence of stenosis, and perform computations of various geometric quantities. This process is fully automated and therefore eliminates inconsistencies and inefficiencies that are a direct result of current semi-automated or complex fully automated systems already in place.

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-000973 — A recombinant oncolytic virus encoding either an adenosine deaminase or heterologous proteins can be used in treatment of a variety of diseases, as the primary purpose of these are to maintain and develop the immune system. A team of researchers at Nationwide Children’s Hospital have found a method that can address the delivery of adenosine deaminase into cancer cells, immune cells and the tumor microenvironment to aid in treatment for any disease or condition associated with adenosine or other associated markers.

TS-000972 — Natural Killer (NK) cells express a range of receptors to activate or inhibit certain cellular behavior to kill cancer cells. When an NK cell is deficient or dysfunctional, the efficiency of the NK cells is severely limited. VISTA is a protein sequence that activates T cells and acts as a moderator for the immune system. It has low-to-moderate expression but has been the target of study by a team of researchers at Nationwide Children’s Hospital led by Dr. Dean Lee. By removing VISTA in expanded NK cells, the inhibitory signal will be eliminated and thus resulting in an enhanced ability of NK cells to target cancers and overcome the immune-suppressive signals for improved cancer immunotherapy.

TS-000971 — The novel disease Coronavirus, also denoted as COVID-19, was recognized by the World Health Organization as an unknown etiology in December of 2019. Severe Acute Respiratory Syndrome (SARS) is a disease that presents flu-like symptoms that is caused by coronavirus (SARS-CoV). The current pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing tremendous economical, emotional, and public health burdens. A team of researchers at Nationwide Children’s Hospital have reengineered a live attenuated recombinant mumps virus to create a novel SARS-CoV-2 vaccine for infants and children under the age of twelve. As vaccination is the most effective strategy to prevent infectious diseases, this development is instrumental to the outcome of the COVID-19 pandemic.

TS-000969 — Gene therapy experts at Nationwide Children’s Hospital have made significant advancements in designing optimal viral vectors for producing Good Manufacturing Practice (GMP)-grade viral vector products. Adeno-associated virus (AAV) serotypes such as AAV1, 2, 2.5, 3, 5, 6, 8, 9 and rh74 have properties optimized by these researchers. Chimeric Antigen Receptor T cells (CAR T) are comprised of an extracellular antigen recognition domain, intracellular T cell activation and co-stimulatory domains. These cells allow for potent and specific targeting of cancer cells, bypassing the need for antigen presentation and T cell receptor recognition. Generating CAR T cells using the process of lentiviral transduction has limitations stemming from the random integration of transgenesis, where oncogene activation, gene silencing, or negative effects on the CAR T antitumor efficacy are possible.

TS-000913 — Peptides can be used to stimulate antigen-specific T cells, allowing activated T cells to be isolated from immune individuals to be used in vaccination or treatment in others. The novel disease Coronavirus, also denoted as 2019-nCoV, was recognized by the World Health Organization as an unknown etiology in December of 2019. Severe Acute Respiratory Syndrome (SARS) is a disease that presents flu-like symptoms that is caused by coronavirus (SARS-CoV). A current process widely applicable to many pathogens uses the Miltenyi Prodigy device. In a study led by Dr. Dean Lee, his team found that this process can be adapted to SARS-CoV-2 using a specialty mix of peptides to isolate T cell immunity.

TS-000912 — There are a few prominent diseases that affect the kidney, such as nephrotic syndrome and diabetic nephropathy. To treat Type II diabetes, there is a readily available pharmaceutical known as pioglitazone that is often used in conjuncture with other compounds to reduce proteinuria in patients with kidney diseases. A team of researchers at Nationwide Children’s Hospital have developed a novel compound to act as a treatment agent in cases of kidney disease. The new design has similar insulin sensitizing effects as pioglitazone as well as its ability to reduce proteinuria. This compound, titled GQ-16, has similar efficacy as traditional Type II diabetes drugs and acts as a new indication for nephrotic syndrome or kidney diseases, with a significant reduction in side effects such as weight gain or adipogenesis.

TS-000906 — Natural Killer (NK) cells express a range of receptors to activate or inhibit certain cellular behavior to kill cancer cells. Additionally, CD38 presenting cells have been used as a marker for cancer stem cells, specifically those that often avoid recognition when common surface antigen processes are used. CARK1 is a phosphorylate that impacts cell growth and development. A team led by Dr. Dean Lee has developed CD38k0 NK cells that they combine with CARK1 to create a series of monoclonal antibodies that targets cancer cells. Along with better cell targeting, this combination improves the efficacy of treatment in comparison to the CAR, NK, or CD38 antibodies as independent components.

TS-000873 — The current timeframe required for current Good Manufacturing Product (cGMP) validation and approval is significant. The delay between development and approval is time intensive and the advancements that can improve treatment can be outdated by the time they reach the market. Genetic modifications would lead to restarting the production and approval process and delaying the introduction of the entry into human trials. Dr. Kevin Cassady and his team found that combinations of oncolytic viruses (OV) can be combined using current, approved cGMP stocks can be employed effectively and subsequently saving time that would have been spent on re-engineering, production, and validation, as well as the expense associated. The clinical outcome would be improved as this new process allows for a more rapid and cost-effective approach to clinical translation using existing stock of virus.

TS-000859 — Nephrotic syndrome (NS) is a common kidney disease found in children that creates an overabundance of protein in the urine, comparable to proteinuria in adults. As of now, there are no approved safe and effective treatment for NS, especially for those whose NS is steroid or multi-drug resistant. A team of researchers have identified a series of new molecular targets for future drug development. Using glomerular transcriptomes and informatic analysis, clinicians will be able to identify immunosuppressive approaches that are distinct from the current procedures.

TS-000857 — CD33 is a receptor that spans multiple membranes and is expressed on myeloid lineage cells and sometimes lymphoid cells. A team of researchers led by Dr. Dean Lee have found a new way to modify existing CD33 processes to provide Natural Killer (NK) cells the additional ability to recognize cell targets expressing CD33. Acute Myeloid Leukemia (AML) expresses multiple antigens, where CD33 is the most common. This new process, labeled as CD33-CAR, shows a significant advantage in targeting AML that presents with CD33, especially in cases that resist unmodified NK cells.

TS-000855 — To diagnose urinary tract infections (UTI), the current strategies use leukocyte esterase, a urine test to look for white blood cells and other signs of infection. which have limited accuracy. These inaccuracies put patients at risk for unneeded antibiotics or delayed treatments, that can allow for UTI progression. Studies have found that the protein levels in urine could differentiate positive and negative results of UTIs. This new testing strategy can improve diagnostics and subsequent patient care.

TS-000854 — Dr. Kevin Cassady and his team have identified an amino acid epitope encoded from Syndecan 4 (SDC4) that binds to a receptor protein on immunosuppressive myeloid and dendric cells called GPNMB. This group has developed a series of fusion proteins including FcGamma (Fcγ) fusions to encode the binding GPNMB-interacting domain, and shared antigens containing epitope tags. They have incorporated the fusion into virus expressed antigens to target myeloid cells in the tumor microenvironment in order to change their functional activity and enhance uptake and processing of antigens. Because SDC4 and GPNMB act as co-inhibitory molecules, they anticipate that fusion proteins will disrupt this interaction, which will enhance T cell activity and could be used as an anti-cancer immunotherapy.

TS-000852 — Gene therapy experts at Nationwide Children’s Hospital have made significant advancements in designing optimal viral vectors for producing Good Manufacturing Practice (GMP)-grade viral vector products. Adeno-associated virus (AAV) serotypes such as AAV1, 2, 2.5, 3, 5, 6, 8, 9 and rh74 have properties optimized by these researchers. The new plasmid named pscCMV-luc2P+ has several improvements including modifications that provide a significant improvement in packaging efficiency of AAV vectors, reduction in potential to form replication competent AAV and the inclusion of the ampicillin resistance gene. Dr. Scott Loiler and his team have made additional optimized vectors for AAVrh74, and AAV9 that allow for more efficient purification and improved CNS transduction, respectively.

TS-000851 — Gene therapy experts at Nationwide Children’s Hospital have made significant advancements in designing optimal viral vectors for producing Good Manufacturing Practice (GMP)-grade viral vector products. Adeno-associated virus (AAV) serotypes such as AAV1, 2, 2.5, 3, 5, 6, 8, 9 and rh74 have properties optimized by these researchers. The new plasmid named pNLRep-Cap1- Kan has several improvements including modifications that provide a significant improvement in packaging efficiency of AAV vectors, reduction in potential to form replication competent AAV and the inclusion of the ampicillin resistance gene. Dr. Scott Loiler and his team have made additional optimized vectors for AAVrh74, and AAV9 that allow for more efficient purification and improved CNS transduction, respectively.

TS-000844 — With the changing climate of online communication, it is imperative that all aspects of healthcare meet the new expectations of virtual care. Dr. Lisa Humphrey, the Director of Hospice and Palliative Medicine at Nationwide Children’s Hospital, has developed a video-based curriculum that includes a series of modules on an online platform to provide expert pediatric palliative and hospice care, as well as additional access to informative videos and expertise.

TS-000842 — In gene expression studies from early oHSV clinical trials, it was found that the cytokine IL27 is a potential target for therapeutic optimization. The cytokine’s expression levels are observed to be directly related to the improvement of the patient survival following treatment that includes an oncolytic HSV. Early data collected by Dr. Kevin Cassady confirms that the virus-based expression correlates with improved survival, and reduced tumor cell growth and has cleared immune cells from the tumors as well.

TS-000841 — Natural Killer (NK) cells express a range of receptors to activate or inhibit certain cellular behavior to kill cancer cells. In a group study it was found that by using TGFb-imprinting, NK cells are driven to a pro-inflammatory phenotype with hypersecretion of IFN-γ, TNF-α, and GM- CSF. These cells, now TGFbi, had decreased degrees of CD38 at both the RNA and the protein level. Studies performed by Drs. Dean Lee and Marcelo Pereira found that CD38 NK cells can be utilized to target CD38+ multiple myeloma patients and improve their progression-free survival by avoiding death of healthy surrounding cells, as well as enhancement of NK cell function.