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-002008 — Effecting three of every 100,000 births, Batten Disease affects the body’s ability to discard cellular wastes like lipids and proteins leading to build up in cells. The build up can cause seizures, vision loss as well as cognitive and mobility impairments. Occupational therapist, Virginia B. Goddard, developed the Batten Disease assessment to better encapsulate patients’ functional abilities. The assessment measures patients’ daily activities, functional fine motor skills, visual abilities, stereognosis abilities, sensory responses and behavior. These categories are broken down into smaller activities and each activity is scored on a scale of 0 to 4: 0 marking minimal to no impairment and 4 marking severe or complete impairment. At the end of the assessment, occupational therapists can calculate a final score out of 76 to measure impairment severity.

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-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-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-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-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-000833 — Psychologist Natalie Truba and Harvard Medical School’s Molly Colvin have developed a new tool to screen and measure the emotional, behavioral, learning, and social needs of pediatric patients diagnosed with Duchenne or Becker muscular dystrophy. Both muscular dystrophies are progressive, inherited disorders that display as muscle weakness that impacts the child’s ability to stand and walk. The intention of the tool is to advise and guide providers who lack direct access to mental health providers during clinic visits. This screening provides recommendations for support, guidance, or for further investigation or intervention for triaging mental, behavioral, or learning concerns.

TS-000737 — 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 whom NS is steroid or multi-drug resistant. Current treatments for NS are only partially effective and often create notable toxicity, but existing thiazolidinediones (TZDs) used for proteinuria in adults have resulted in reduction of proteins found in the urine. Introducing the TZD pioglitazone (PIO) to a trial study conducted by Dr. William Smoyer, pediatric patients with multi-drug resistant NS showed notable proteinuria reduction in comparable time periods, both before and after the addition of PIO in their medical regimens.

TS-000635 — Infectious peritonitis is a serious complication in patients undergoing chronic peritoneal dialysis (PD) leading to patient morbidity and mortality. Currently available, non-specific diagnostic criteria of peritonitis can lead to missed /over-diagnosis. Researchers at Nationwide Children’s Hospital have discovered more sensitive and specific biomarker for peritonitis in the PD population that entails measurement of antimicrobial peptide levels. This new process will aid practitioners in early, accurate diagnosis of acute peritonitis in patients undergoing PD.

TS-000621 — Traumatic brain injury (TBI) is a leading cause of acquired disability in U.S. children and adolescents. Impairment of executive functions post-TBI has broad and profound implications for everyday life of pediatric patients, and the development of effective rehabilitation strategies is of significant clinical importance. Researchers at Nationwide Children’s Hospital have developed virtual reality (VR)-based programs for assessing cognitive function and providing subsequent rehabilitation. This pediatric TBI assessment software provides VR-based cognitive-assessment tasks and an additional training platform that pairs with the Oculus Rift virtual reality viewer. The training program is designed with a series of environmentally-enriched three-dimensional cognitive exercises that aid in rehabilitation of executive core functions among pediatric patients with TBI in a highly controlled, safe, and automated manner.

TS-000596 — Spinal Muscular Atrophy (SMA) is a severe neuromuscular disease and the leading genetic cause of infant mortality. Moreover, existing treatments suffer from notable floor and ceiling effects and also poorly discriminate improved motor performance in patients. To circumvent these challenges, researchers at Nationwide children’s have developed the Neuromuscular Gross Motor Outcome (GRO) worksheet. The GRO worksheet is a gross motor outcome measure designed to assess whole body strength, motor development and function for all levels of ability across the lifespan in those diagnosed with SMA. Hence, the GRO worksheet is the ideal outcome measure tool for SMA or similar conditions to answer the need to quantity gross motor ability across a wide age span.

TS-000556 — Oncolytic viruses (OVs) target cancer cells, killing them from the inside. As the contaminated cancer cells die, the biproducts develop additional infectious components that continue to destroy the tumor. Dr. Kevin Cassady and his team have found that using OV-based “shared” antigen expression allows the immune system to recognize these antigens and improves the capacity of the immune system to fight tumor activity. Shared antigen expression includes proteins that are overexpressed by many tumors. They have been able to construct additional OVs that improve the immune targeting glioma and its associated antigen, IL13Ra2. This group is simultaneously investigating other ways enhance the anti-glioma activity by combining OVs with Chimeric Antigen Receptor-targeted T cells directed against IL13Ra2. In pre-clinical trials, this combination has produced improved anti-tumor activity with lower doses and safe to the patient.

TS-000513 — Dystrophinopathies are a group of disorders caused by mutations in the DMD gene which codes for dystrophin, the vital, muscle-specific structural protein. Currently, there is no cure for muscular dystrophy, and patients only rely on palliative care options. Our gene therapy researchers at Nationwide Children’s Hospital have developed an AAV-mediated gene editing method for correcting deleterious DMD mutations in affected patients. This therapy uses a homology-independent targeted integration (HITI) to replace any missing or aberrant exons in affected patients; therefore, correcting the underlying cause of DMD. This therapy will be developed to stop the progression of muscle wasting and fibrosis in individuals with DMD mutations that result in muscular dystrophy via permanent correct of the underlying cause within muscle tissue by replacing missing or aberrant exons using HITI. Advantages By developing AAV-Mediated HITI gene editing for correction of diverse DMD mutations in patients with muscular dystrophy, we can potentially cure BMD and DMD patients. These patients currently have no palliative care options. Our compositions of matter for this approach (i.e. genomic target region, guide-RNA sequences, donor DNA sequences) are new. Stage of Development Proof of concept studies completed Intellectual Property Provisional Patent Pending

TS-000497 — Huntington’s Disease (HD) is a late onset progressive neurodegenerative disorder that results in death in 10-15 years after the first sign of symptoms. Existing oligonucleotides (AONs) based therapies are imperfect as they knockdown wildtype protein, require consistent re-injections, and use potentially harmful molecules. Gene therapy experts at Nationwide Children’s have devised a gene therapy approach that uses a specific snRNA to stably and safely reduce the highly pathogenic protein HTT. By enabling a continuous expression of the therapeutic RNA in the nervous system (and other targets), this technology may delay the age of onset, slow symptom progression, and reduce symptom severity of HD. Hence, it has the potential to become the optimal therapeutic strategy for the treatment of HD.

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-000470 — CuATSM is a small molecule which facilitates the delivery of copper to cells containing damaged mitochondria, the cell compartments responsible for the production of energy. Currently, CuATSM has shown success in clinical trials for treating patients with ALS. Neurodegenerative disease experts at Nationwide Children’s Hospital have elucidated novel mechanisms of action through which the small molecule can treat disorders caused by oxidative stress, mitochondrial dysfunction and elevation of stress response systems. Through these studies, our disease experts have identified several new indications which could be treated with this small molecule compound.

TS-000438 — Gene therapy experts at Nationwide Children’s have developed an AAV-mediated CRISPR/Cas9 gene editing method for the correction of exon duplications in patients with DMD (Duchenne muscular dystrophy). This therapy has the potential to permanently corrects DMD by stopping and potentially reversing the progression of muscle wasting and fibrosis in affected individuals. Currently about 11% of DMD cases are caused by exon duplications and our experts plan to use this invention to correct for this underlying cause within muscle tissues.

TS-000433 — Flying phobia is a highly prevalent anxiety disorder, which causes sufferers significant distress and life interference. There are multiple interventions addressing flying anxiety provided through airports, commercial airlines as well as online materials. However, these services either charge fees or do not provide any aircraft/airport simulation experience. Inventors at Nationwide Children’s Hospital have designed a unique workshop curriculum which includes PowerPoint slides, a video tape and participant handouts and experimental activities. This educational intervention facilitates increasing tolerance of and comfort with air travel.

TS-000372 — Respiratory syncytial virus (RSV) is the most frequent cause of lower respiratory disease and hospitalization in infants, but there is currently no vaccine available to prevent or treat RSV disease. Researchers at Nationwide Children’s Hospital and The Ohio State University have developed a novel method for designing RSV vaccines using a Vesicular Stomatitis Virus (VSV) vector. VSV is attenuated in humans, so it can infect people and express inserted genes without causing disease. Additionally, VSV grows to high titers in culture, allowing for efficient vaccine production.

TS-000358 — Congenital Muscular Dystrophy Type 1A (CMD1A) usually presents in the neonatal period with marked muscle weakness and severe hypotonia. CMD1A patients show deficiency in laminin-alpha2 (LAMA2) protein caused by the genetic mutations leading to weaker and unstable muscle tissue. Gene therapy experts at Nationwide Children’s Hospital have developed a gene and protein therapy approach enabling delivery of key domains of LAMA2 using adeno-associated virus (AAV). In addition, our experts have engineered fusion proteins that assist in anchoring LAMA2 to the muscle membrane thereby improving the muscle-matrix interaction and muscle integrity.

TS-000338 — Worldwide, malaria affects 2 million individuals annually. Cerebral malaria is the most severe neurological manifestation of malaria with case fatality rates ranging from 15-40%. Researchers at Nationwide Children’s Hospital have developed a method for using Transcranial Doppler to detect distinct waveform morphologies and identify pathogenic mechanisms leading to neuronal injury in children with cerebral malaria. Benefits: By identifying the specific sub-type of cerebral malaria, clinicians will be able to treat patients for their particular pathology, improving therapeutic outcomes. Stage of Development Following proof of concept studies, the researchers evaluated its use clinically in over 180 children with cerebral malaria and 140 control patients. The published study validated the use of transcranial Doppler ultrasound (TCD) in identifying distinct patient phenotypes which can serve as a guide for appropriate therapeutic regimens to specifically target the pathologic sub-type of cerebral malaria. Potential Applications/Markets: TCD can be used to identify pathogenic mechanisms leading to neuronal injury in children with cerebral malaria. We found 5 distinct waveform morphologies that are related to 5 different pathogenic mechanisms in children with malaria. To date, all clinical trials aimed at improving neurologic outcomes of these children have failed. We believe they have failed because drugs are not targeting the correct pathogenic mechanism in each child. In the future, TCD will be able to be used to determine which pathologic category individual children fall in and determine appropriate treatment strategies for them (clinical use). Additionally, this information is imperative to all future therapeutic trials looking at adjunctive agents aimed at the reduction of neurologic injury in these children research tool, probably before the clinical use). Opportunity/Seeking: Commercial Partner Licensing

TS-000329 — There is currently no vaccine available for protecting against Zika virus (ZIKV) infection and disease. Researchers at Nationwide Children’s Hospital and The Ohio State University have developed novel candidate ZIKV vaccines that use vesicular stomatitis virus to express ZIKV proteins. The protection conferred by our vaccines does not rely on antibodies against the ZIKV envelope protein, eliminating the potential problem of antibody dependent enhancement of other species of flavivirus. Our candidate vaccines are highly attenuated while still inducing a protective immune response against ZIKV infection.

TS-000308 — Absence of the dystrophin protein leads to the severe muscle disorder Duchenne Muscular Dystrophy (DMD). Nearly asymptomatic patients have been identified to produce a functional N-terminal truncated dystrophin protein. Gene therapy experts at Nationwide Children's Hospital are developing a U7-snRNA exon skipping strategy to facilitate expression of a truncated dystrophin protein for patients carrying mutations within exon 6 to 9 of the DMD gene, rendering their dystrophin nonfunctional. Our experts have effectively skipped exon 8 in patient-derived cell lines and in turn produced a functional truncated dystrophin protein product.

TS-000303 — Despite the high prevalence of mental health, many cases go without treatment- in part because their disorders go undiagnosed. Scientists at Nationwide Children’s Hospital have developed a computerized screening tool for behavioral health that is able to administer and score a set of mental health symptom questionnaires. This web application enables earlier identification of mental health disorders leading to earlier care.

TS-000243 — Researchers at Nationwide Children’s Hospital have developed a novel method for increasing the patency of biodegradable, synthetic vascular grafts. Administration or controlled release of one or more cytokines or chemokines was found to promote outward tissue remodeling of the vascular grafts and vascular neotissue formation. As a result, this method does not require cell seeding of the vascular graft, eliminating many problems associated with cell seeding such as contamination, loss of clinical utility due to added time for cell expansion, and difficulty in obtaining healthy autologous cells from diseased donors.