Wednesday, 07/26/2017

Funded Technologies

Technology Title Technology Type Disease Area Description Indication Center / Hub Point of Contact
A New Standard of Care for Implant Bed Preparation Utilizing an Innovative Drill Bit Technology Medical Device Dentistry The objective is to develop a new surgical drill bit that is capable of replacing the current standard of clinical implant bed preparations and surgical bone drilling. The new predicted standard allows for a dramatically shortened and more precise implant protocol, leading to a significant reduction in bone necrosis, enhanced early bone apposition, and ultimately immediate functional loading (IFL) capability of implants. The specific aim is to design a drill bit as a multi-diameter bit for a one-stage implant site preparation, instead of using a sequence of 4 drill bits in average with increasing diameters. This manifests a faster rate of penetration, lower surface and down hole torque, lower down hole vibrations, reduced material wear, higher efficiency and higher stability in all directions. Medical applications include implant, orthopedic and neurosurgeries. Implant site preparation LIBH image of external link icon Li Liu
Sean Boykevisch
A novel glioblastoma drug - Oncolytic virus PV1-Mono-Cre Biologic Drug Cancer Glioblastma multiforme (GBM) is one of the most deadly cancers with a median survival of 15 months despite of traditional surgery, radiotherapy and chemotherapy treatment. The only approved drug that is relative effective in extending the survival expectancy is temozolomide. However, the drug does not improve the overall survival rate, which remains less than 10% in 3 years. Therefore, a novel glioblastoma drug is urgently needed. Recently, the success in using the oncolytic recombinant poliovirus PVS-RIPO to treat glioblastoma patients, a procedure which was designed in our laboratory in Stony Brook, has prompted us to develop our novel recombinant virus design PV1-Mono-Cre in GBM model. PV1-Mono-Cre was highly effective as an oncolytic agent against neuroblastoma in both tissue cultures and transgenic mice model. Our goal in this project is to test PV1-Mono-Cre's efficacy in GBM cell lines and animal model. Glioblastoma LIBH image of external link icon Li Liu
Sean Boykevisch
Azasteroids for Combination anti-TB therapy Small Molecule Drug Infection Control, HIV/AIDS Using a privileged pharmacophore, our long-term goal is to develop a more effective drug-sensitive and drug-resistant TB combination therapy. The proposed therapy will reduce time of treatment, and consequently reduce treatment costs and improve treatment outcomes. We have identified a drug scaffold which has high host in vivo stability, low host toxicity, and excellent host bioavailability to develop as an anti-TB therapeutic and which is protected by a use patent. The specific aims in this proposal are to 1) improve the potency of lead compounds; 2) to analyze and if necessary, improve the mycobacterial metabolic stability of the most effective lead compounds from aim 1; and 3) to determine the host pharmacokinetic profile for the top lead compounds. The targeted outcomes for the end of the granting period are a) to be positioned to transition 3 top lead candidates of low toxicity and excellent ADME profile from in vitro to in vivo testing; and b) to improve the IP position of the products prior to commercialization. Tuberculosis LIBH image of external link icon Li Liu
Sean Boykevisch
NEW-HARP: A highly sensitive avalanche selenium detector for time-of-flight (TOF) positron emission tomography (PET) Diagnostics Device Medical Imaging The signal to noise ratio (SNR) of positron emission tomography (PET) can be substantially improved by time-of-flight (TOF) readout technique. The ultimate TOF detector is one with time resolution ?t < 10 picosecond (ps). Such a detector has still not been realized. Existing commercial systems utilize bulky and expensive photomultiplier tubes (PMTs) which are based on the complicated planoconcave photocathode and yet can only achieve ?t ~ 500 ps. Silicon (Si) photomultipliers (SiPMs) are rapidly developing and have achieved better ?t than PMTs (i.e., SiPM ?t ~ 100 ps). However, they suffer from poor photon detection efficiency, optical crosstalk, small area, poor uniformity, and high cost. The main goal of this proposal is to fabricate and characterize a novel avalanche picosecond detector that consists of (1) a sub- strate with nano-pattern multi-well electrode structure and (2) amorphous selenium (a-Se) photoconductive layer with avalanche multiplication. We call this detector NEW-HARP: Nano-Electrode multi-Well High- gain Avalanche Rushing Photodetector. The key advantages of NEW-HARP are uniform scalability over large area at substantially lower cost compared to crystalline solids, ~90% detection efficiency in the blue wavelength, and compatibility with complementary metal-oxide semiconductor (CMOS) technology. PET LIBH image of external link icon Li Liu
Donna Tummunello
Orthovoltage X-Ray Minibeams: Brain tumor therapy with tissue-sparing incident beams Medical Device Cancer Current radiation therapy methods of brain tumors using megavolt (MV) x-rays produce neuro-cognitive deficits. The main reason is that the dose produced by these high-energy x-rays in the brain are not optimally concentrated on the target but expose much brain tissue proximal, lateral, and distal to the target. Although orthovoltage x-rays are known to have a smaller dose spread around the target, they have not been used for radiation therapy for the last 60 years because of their limited tissue penetration. Our method, Orthovoltage X-ray Minibeams (OXM), segments the incident beams into arrays of parallel, thin (0.3 mm) planar beams (minibeams), which are known to spare tissues from synchrotron x-ray studies. As minibeams penetrate tissues they gradually broaden to merge with their neighbors, producing a solid beam at the proximal side of the tumor. Our physical feasibility studies suggest that OXM can spare the cortex and temporal lobes and reduce integral brain dose. We propose to use the minipig brain as a model to compare the dose to non-targeted brain produced by OXM and by 6-MV x-rays in ablating a 2-cm target in the brain. Brain Tumor LIBH image of external link icon Li Liu
Donna Tummunello
3D Shoulder Motion Measurement Device (The MnMotion System™) Diagnostic device, Combination Product including mHealth product and research tool Musculoskeletal or neurologic movement disorders, initially specific to shoulder joint dysfunctions To develop a cost-effective, accurate, precise, and objective 3-dimensional motion measurement for clinicians treating patients or athletes with shoulder pain or motion disorders. Physical Medicine MN-REACH image of external link icon Amy Moore
A Bio-Inspired Transcatheter Mitral Valve Device Heart This proposed project will develop and test the first transcatheter bileaflet mitral valve with dynamic annulus, and its delivery system for transapical implantation. This bio-inspired mitral valve system will offer most of the advantages that a native bileaflet mitral with dynamic annulus has to offer for left ventricular function. Heart Valve Disease UC CAI image of external link icon Alvin Viray
A Biomimetic Human Platelet Bioreactor Therapeutic Blood To develop a microfluidic bioreactor that can produce human platelets from human induced pluripotent stem cells. These projects are considered too early to have well defined clinical indications. B-BIC image of external link icon Erin McKenna
A Blood Coagulation Sensor for Point of Care Use Device Blood To develop prototypes and refine designs for a portable Optical Thromboelastography (OTEG) instrument and disposable cartridges for blood coagulation testing. These projects are considered too early to have well defined clinical indications. B-BIC image of external link icon Erin McKenna
A first-in-class RalGEF inhibitor as an anti-Ras drug Therapeutic Cancer This application proposes the development of new agents to block the activities of the Ras oncoprotein via a novel strategy. The investigator has identified small molecules that block the interaction between Ras and RalGEFs, and these lead compounds suppress metastasis in preliminary animal models. Ras-driven cancers UofL-ExCITE image of external link icon Paula Bates
A Manganese Alternative to Gadolinium for MRI Contrast Therapeutic Blood This project will develop a manganese based MRI contrast agent to be used in a manner similar to existing gadolinium based contrast agents (GBCAs). Animal studies demonstrating equivalence to GBCAs, along with quantifying drug metabolism, pharmacokinetics, acute and sub-toxicity, will be completed to support advancement towards achieving a clinical product. Use in medical imaging B-BIC image of external link icon Erin McKenna
A Nanophotonic Platform for Rapid and PCR-free Detection of Bacterial and Fungal Infection Combination Cardiovascular This projects features the use of an ultrasensitive nanophotonic detection device for the detection of fluorescence that is a marker for the DNA of bacterial pathogens that lead to infections in humans. The desired product will be a "point-of-care" DNA diagnostic platform based on optical amplification - without requiring a polymerase chain reaction - that will allow the implementation of protein and DNA assays at a patient's bedside, in a matter of minutes. Multiple bacterial and Fungal infection detection UC CAI image of external link icon David McGee
A Small Molecule Inhibitor of 15-PGDH Markedly Accelerates Hematopoietic Reconstitution Following Hematopoietic Stem Cell Transplantation Therapeutic Blood Clinical development of a first in class inhibitor of 15-PGDH, secured with 4 patent filings, and which has shown markedly accelerated hematopoietic reconstitution following bone marrow transplantation in murine models. 15-PGDH enzyme activity catalyzes the first and rate limiting step in prostaglandin degradation, and prostaglandins, particularly PGE2, are active mediators in supporting hematopoiesis. Hematopoietic Stem Cell Transplantation NCAI-CC image of external link icon Mark Low
Activated Platelet Time: an Improved Factor VIII Assay Diagnostic Blood Project will develop a novel factor VIII activity assay that will extend the range of the currently used assay and increase its sensitivity to inhibitory antibodies, thereby providing significant clinical benefit by creating a result that is likely to better correlate with bleeding risk of the patient. Factor VIII-related hemophilia B-BIC image of external link icon Ron Blackman
Advanced Development of Intravenous Oxygen Microparticles Therapeutic Lung Project goal is to produce oxygen carrying microparticles (OMP) that are capable of safe, intravenous delivery oxygen to deoxygenated RBC in the bloodstream during acute hypoxic events. Project will focus on developing the process technologies needed to scale up production of the OMP. Alternative OMP biomaterials will also be investigated for suitability. Systemic oxygen deprivation caused by acute respiratory failure B-BIC image of external link icon Ron Blackman
Advancing Rapid Malaria Detection Technology Towards Commercialization Diagnostic Blood The goal of this project is to develop a low cost, highly sensitive, rapid diagnostic test for malaria suitable for portable, field-deployable use. The test is based on detection of an iron containing particle, hemozoin, that is a bi-product of blood cell digestion present in cases of malaria parasite infection, utilizing magneto-optical detection technology to identify infected blood samples. Preliminary laboratory data indicates that this technology can quantify the level of parasites in a blood sample in under 1 minute, for $0.09 per sample, with an accuracy of 94%. Enhancements to the design to be pursued in this project may enable improvement that could decrease the current minimum detectable level by 5 fold, thereby providing the possibility of identifying asymptomatic malaria carriers, and curtailing spread of malaria infection. Malaria NCAI-CC image of external link icon Mark Low
Augmented Visualization for Minimally Invasive Cardiovascular Surgery: AugMed3D Device Heart This project will advance the development of a software application, AugMed3D, that enables Augmented Reality (AR) guidance during minimally invasive cardiovascular surgery. Minimally invasive aortic valve replacement/repair (AVR) has been selected as the target AR application. An initial video see-through AR software prototype has been implemented to verify registration and visualization modules invented and developed in our lab. The AR application will be migrated (ported) to an optical see-through eyewear devices such as SensoryWear (Magic Leap) or HoloLens (Microsoft) for further verification and validation in simulated clinical use. This project will prepare for a future clinical study including intraoperative evaluation of the AugMed3D for minimlly invasive AVR. Aortic Valve Surgery NCAI-CC image of external link icon Mark Low
CD8 T cell immunotherapy to functionally cure HIV Biologic Drug HIV/AIDS To provide proof-of-concept for a CXCR5/CAR immunotherapy that targets the follicular reservoir of HIV-producing cells HIV / AIDS MN-REACH image of external link icon Amy Moore
Clinical Validation of an Unbiased Next-Generation Sequencing Diagnostic Assay for Pneumonia in a CLIA-Certified Laboratory Diagnostic Respiratory More than 30% of cases of pneumonia in hospitalized patients remain undiagnosed despite extensive conventional testing. Failure to diagnose these serious infections in the timely fashion leads to ongoing nosocomial transmission and increased mortality. This project is focused upon the development of a rapid unbiased assay for diagnosis of pneumonia in a CLIA certified facility. The data will also be analyzed to identify all of the pathogens. As such it will enable appropriate treatment decisions and further understanding of pathogen etiology in pneumonia. Pulmonary microbiome detection UC CAI image of external link icon Sunita Rajdev
Confocal Microscopy for Intraoperative Discrimination of Cardiac Conduction Tissue Device Heart To establish real-time fiber-optics confocal microscopy (FCM) as an intraoperative imaging modality in cardiac surgery, particularly in pediatreic open-heart surgery. Cardiac surgery imaging for indentification of conduction tissue. B-BIC image of external link icon Erin McKenna
Continuous lactate monitor for early indication of resuscitation in trauma and sepsis Device Blood High mortality rates continue to persist in many patients with critical conditions such as sepsis, and trauma. Treatment in these cases is often aimed at stabilizing patient parameters such as vital signs. However, by the time these parameters change, it is often too late to intervene effectively. A compendium of evidence over the last few decades has shown that lactate concentration is one of the most powerful early predictors of outcome in many critical conditions, and that lactate concentration can be used to improve patient survival by directing therapy more effectively. Lactate-guided therapy is difficult or impossible to utilize in clinical practice however because current technologies allow only intermittent lactate measurements, thus failing to provide adequate and timely information about lactate changes. As such, a continuous measurement of lactate is desired to provide real-time lactate concentration. This project advances the development of our technology that will provide hands-free continuous lactate monitoring. Lactate Monitoring UC CAI image of external link icon Casie Kelly
Custom Airway Stent Project Device Lung The primary goal of this NCAI funded project is to develop, manufacture, and obtain FDA clearance for use of custom, patient-specific airway stents. A patient-specific stent, designed to fit a patient's specific anatomy and disease state by using a CT scan of the patient's airway and custom software to prescribe the size, shape, and angles of any branching of the stent, may mitigate stent migration, granulation tissue surrounding the stent, and perhaps reduce risk of infection. Patient-specific stents may also reduce operating time by eliminating the need for intraoperative modification of standard stents to match patient anatomy and extend the useful life of the stent. In this project, we will 1) complete design and validation of software for custom airway stents; 2) perform initial build out for manufacture of the patient specific stents, 3) perform the safety and efficacy testing required for FDA clearance, and submit to FDA. Airway stenting NCAI-CC image of external link icon Mark Low
Defining a next-generation local anesthetic agent Small Molecule Drug Analgesia/Anesthesiology This project proposes to develop a new type of motor-sparing local anesthetic and is based on the discovery of an agent that blocks signal conduction in sensory neurons but spares conduction in motor neurons to some degree. The agent in question is structurally distinct from existing local anesthetics (which are all cocaine-related) and appears to have a novel mechanism of action. This agent is already FDA-approved for other unrelated purposes. The proposed product may provide a safer, more effective, and more convenient alternative to existing local anesthetics and could be useful in a variety of clinical settings, e.g. dentistry, obstetrics, ophthalmology, or pain management. Multiple UofL-ExCITE image of external link icon Paula Bates
Detection of Thrombin Generation for Acute MI Monitoring Diagnostic Heart Current standard of care for patients with chest pain and suspected acute coronary syndromes (ACS) involves considerable observation and extensive clinical reassessment of serum cardiac biomarkers for patients with intermediate risk. For safety reasons, few patients with an atypical presentation for ACS are rapidly discharged from the cardiac observation units (COUs). Physicians lack a tool that can quickly and accurately stratify risk and rule out ischemic cardiac chest pain. CardioPaint©, a non-invasive diagnostic tool for ruling- out ischemic heart chest pain from intermediate-risk patients admitted in COUs with suspected ACS for safe discharge, and rule-in for further and more effective intervention. CardioPaint© is a peptide-based technology activated by thrombin at sites of blood coagulation for imaging and detection of blood clots. Acure Coronary Syndrome diagnostic UC CAI image of external link icon Kristin Agopian
Developing a Biocompatible Elastic Sealant Device Lung To develop a cost-efficient and biocompatible sealant for repairing soft tissues such as wounded lung tissues based on a light-responsive material, methacrylated gelatin (GelMA), formed by methacrylation of gelatin. Lung sealant, surgical sealant indications/applications. B-BIC image of external link icon Erin McKenna
Developing a Personalized CRT Approach with Cardiac CT Kinematics Other - Healthcare IT Heart To develop a comprehensive CT-kinematic based CRT software program which can guide left ventricular (LV) lead placement to target site of latest activation and avoide regions of scar, as well as determine dyssynchrony for prognosis. These projects are considered too early to have well defined clinical indications. B-BIC image of external link icon Lesley Watts
Development of 6-Phosphofructo-2-Kinase/Fructose-2, 6-Bisphosphatase-4 (PFKFB4) Inhibitors for the Treatment of Cancer Therapeutic Cancer The proposed product is a small molecule that targets the glycolytic pathway, which is accelerated in most cancer cells in order to satisfy their increased anabolic and energetic requirements. The investigator has identified a lead small molecule that is a specific inhibitor of PFKFB4, an enzyme that plays an important role in glycolysis in non-small cell lung cancer cells. Cancers that are driven by high rates of glycolysis, including non-small cell lung cancer. UofL-ExCITE image of external link icon Paula Bates
Development of a method to store refrigerated platelets for human transfusion Other Blood This project is directed towards development of a novel method of platelet storage for which our team of investigators has obtained strong pre-clinical data on refrigerated murine and human platelets. The project will extend the analysis of human platelet storage in the refrigerated conditions and analyze survival and efficacy in non-human primate models in vivo. This method to store viable platelets by refrigeration consists of a novel combination of chemical inhibitors of several members of the Rho GTPases for ex-vivo use in a medium designed to extend the shelf-life of refrigeration stored platelets that is an urgent unmet medical need. Completion of this project will generate crucial data to demonstrate its efficacy and safety in stored human and primate platelets and will move the project to a successful FDA IND proposal and for commercialization. Blood Platelet Storage NCAI-CC image of external link icon Mark Low
Development of a Self-Regenerative Hybrid Heart Valve Device Heart This research aims to develop and test the first hybrid tissue-engineered heart valve. The hybrid heart valve leaflets are composed of a super-thin mesh of Nitinol that is tightly enclosed by multiple layers of patient's own cells making a living implant possible within the heart. Heart Valve Disease UC CAI image of external link icon Alvin Viray
Development of an Implantable Intracardiac Soft Robotic Right Ventricular Ejection Device Device Heart To develop an implantable intracardiac device based on soft robotic actuation that delivers a dynamic pulsatile force timed to the cardiac cycle that is tailored specifically to augment blood ejection from the RV (RVED). Provide support for patients experiencing right ventricular heart failure as a bridge to transplant. B-BIC image of external link icon Erin McKenna
Development of BET Bromodomain Inhibitor Drugs for Human Heart Failure Therapeutic Heart Using the NCAI funding, we are focusing on developing a pharmacological bromodomain and extra-terminal (BET) bromodomain inhibition as a novel therapeutic strategy for human Heart Failure (HF). HF is a leading cause of healthcare expenditures, hospitalization and mortality in the United States. Despite current standard of care, a diagnosis of HF carries a five-year mortality of ~40%, highlighting an urgent need for new therapeutic approaches. A team led by Dr. Haldar recently demonstrated that BET bromodomains, a conserved family of epigenetic "reader" proteins, are critical mediators of pathologic cardiac hypertrophy and HF pathogenesis. Using next generation BET inhibitor drugs, the current project will directly support the development of pharmacological BET bromodomain inhibition as a novel therapeutic strategy in human HF. Our plan for year 1 is to use murine models to address important therapeutic questions, such as safety, toxicity and dosage determinations that will support feasibility of porcine and first-in-human HF studies in subsequent stages. Heart Failure NCAI-CC image of external link icon Mark Low
Development of small molecule inhibitors specific for IL-17A-mediated pulmonary inflammation Therapeutic Lung This project is to further optimize a small molecule inhibitor (A18) specific for IL-17A-mediated pulmonary inflammation for better bioactivities with ultimate goal to develop a new therapeutic agent for treating severe and steroid-resistant asthma. Elevated levels of IL-17A have been detected in asthmatic lung tissues and are positively correlated with neutrophil-predominant severe and steroid-resistant asthma. Deficiency of IL-17A signaling components leads to diminished neutrophilic pulmonary inflammation and airway hyper-responsiveness (AHR) in both allergic- and non-allergic asthma mouse models. Therefore, IL-17A signaling is a promising therapeutic target for inhibiting IL-17A-dependent pulmonary inflammation, particularly for the treatment of severe and steroid-resistant asthma. Through computer-aided virtual screening based on the crystal structure of IL-17 RA/IL-17A complex, we have identified one small molecule lead compound, A18 that exhibited excellent ability to inhibit IL-17A binding to IL-17RA. To achieve the goal, we will optimize the structure of A18 for better bioactivities; validate A18 and the best A18 derivative in IL-17A-induced pulmonary neutrophilia and Aspergillus-induced severe asthma model. Asthma NCAI-CC image of external link icon Mark Low
Development of SMASH technology as a next-gen sequencing diagnostic for congenital heart disease Combination Cardiovascular Health Technology for "Short Multiply Aggregated Sequence Homologies" ("SMASH") which has the potential to provide a drastic improvement in detection of de novo and inherited copy number variants in congenital heart disease. This would help provide geneticists with earlier information on the presence of potentially harmful (or helpful) mutations in newborn infants Congenital heart disease LIBH image of external link icon Diane Fabel
Electric Nitric Oxide Generation for Medical Purposes Therapeutic Device Lung To develop and test a portable, affordable, and lightweight NO generator. Inhaled NO treatement for neonates with persistent pulmonary hypertension of the newborn (PPHN) and for adult patients with chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), or chronic pulmonary arterial hypertension (PAH) B-BIC image of external link icon Erin McKenna
Elimination of Pathogenic IgE in Cystic Fibrosis Biological Therapeutic Lung Project will continue the development of an IgE neutralizing biologic designed to suppress the inflammatory allergic response to aspergillosis in the lungs of CF patients. The therapeutic is a modified version of an IgE receptor that acts as a decoy to prevent binding of IgE with its target cell while also blocking aggregation of bound IgE to prevent degranulation. Allergic bronchopulmonary aspergillosis in Cystic Fibrosis patients B-BIC image of external link icon Ron Blackman
Erythroferrone antibodies and assays to support drug development for anemia and iron disorders Combination Blood The project is focused on the development of antibodies against erythroferrone, a newly discovered regulator of iron metabolism. These antibodies will have likely utility for the differential diagnosis of anemias and iron overload disorders, and as companion diagnostics for new agonists and antagonists of the erythroferrone pathway that are under development. Anemias and iron overload disorders. Companion diagnostics for therapeutics directed at the erythroferrone pathway. UC CAI image of external link icon Ben Dibling
Evaluating SynthoPlateTechnology in Porcine Traumatic Bleeding Therapeutic Blood We have developed a unique Synthetic Platelet technology (the SynthoPlate) that integrates natural platelet's injury site selective adhesion and aggregation functionalities on a single synthetic platform. Our prior research has resulted in establishing superior hemostatic efficacy via emergency and prophylactic administration in mouse bleeding models. Building on this we will advance the technology towards translation by testing its hemostatic efficacy and systemic safety in a large animal (pig) bleeding model (trauma). Blood Platelet Transfusion NCAI-CC image of external link icon Mark Low
EYA Inhibitors in the Treatment of Peripheral Vascular Disease and Pulmonary Arterial Hypertension Therapeutic Lung The goal of this NCAI funded project is to validate a small molecule treatment for pulmonary arterial hypertension (PAH) that targets a newly identified molecular pathway involved in survival of hypoxia-damaged cells, hence addressing the molecular basis for the vascular remodeling in PAH. There is a large unmet need to identify new therapeutic targets in the treatment of PAH, a progressive, life threatening disorder. Approximately 50% of patients diagnosed with PAH die within 5 years. Current treatments do not inhibit pulmonary remodeling, a key pathology of PAH. Furthermore, they are associated with significant hospitalization cost. Recent evidence points to a role of DNA damage repair in PAH in pulmonary remodeling. EYA protein plays a fundamental role in promoting survival of cells after DNA damage. This project is focused on developing EYA tyrosine phosphate inhibitor as a novel and druggable option for the development of new PAH therapeutic. Using our lead compound, we plan to develop potent and pharmacologically favorable compounds, and to perform pre-clinical assessment of these agents in an animal model of PAH. Pulmonary Arterial Hypertension NCAI-CC image of external link icon Mark Low
fMRI Dynamic Phantom for Improved Detection of Resting State Brain Networks Research Tool Medical Imaging, Neurology Device to provide quantitative feedback to users in optimizing fMRI acquisition parameters for dynamic fidelity. Will identify scanner-induced distortion produced for a particular set of acquisition parameters, and then will employ algorithms to automatically correct that distortion. Task-free fMRI calibration LIBH image of external link icon Diane Fabel
Gene-modified mesenchymal stem (stromal) cells for the Treatment of the Acute Respiratory Distress Syndrome Therapeutic Lung The acute respiratory distress syndrome (ARDS) is a major cause of morbidity and mortality in critically ill patients. This project is designed to develop a novel therapeutic based on enriched conditioned media from gene modified human bone marrow derived mesenchymal stem cells (MSC). There is an ongoing phase 2 clinical trial of MSCs for ARDS, but experimental data indicates that the conditioned media of MSC may also be effective. This project will enrich the conditioned media with transfection into MSCs of three genes that appear to be responsible for much of the therapeutic efficacy of MSCs themselves. The efficacy of the cell-free conditioned media will be tested in both in vitro and in vivo models. Acute Respiratory Distress Syndrome (ARDS) UC CAI image of external link icon Debbie Alexander
HemeChip: Point-of-Care Sickle Cell Disease Diagnosis in Low Resource Settings Diagnostic Blood The objective of this NCAI-CC project is to translate HemeChip technology as a point-of-care (POC) platform for diagnosing hemoglobin disorders, specifically sickle cell disease (SCD). In this project, we focus on translating the technology in resource-limited countries of the Sub-Saharan Africa, where the prevalence of SCD is the highest. HemeChip technology addresses a real unmet need for low-cost, easy-to-use, POC newborn screening platforms for SCD in low-income and under-resourced environments. This NCAI-CC project will focus on large volume manufacturing by a third party, field testing, and regulatory approval pathway in Sub-Saharan Africa. Sickle Cell Disease NCAI-CC image of external link icon Mark Low
Hydrogel device for preventing cardiac adhesions post-cardiothoracic surgery Device Heart Two main approaches exist for reducing or attempting to prevent cardiac adhesions: pharmacological therapy and physical barriers. Drugs that prevent or reverse adhesion processes disrupt biochemical pathways of inflammation and fibrin deposition. Unfortunately, these processes are also vital for wound healing. We propose a new approach to prevent postsurgical cardiac adhesions using rapidly forming poly(ethylene glycol) (PEG) hydrogels that are cross-linked by oxime bonds. As part of this proposal, we will demonstrate proof-of-principle for using the PEG oxime system to prevent cardiac adhesions in a rat cardiac surgery model. Cardiac adhesions post-cardiothoracic surgery UC CAI image of external link icon Denise Lew
Impedance-Based, Continuous Hematocrit Monitoring in the Trauma Population Diagnostic Blood To develop and validate an impedance-based approach to the continuous, real-time measurement of hematocrit in traumatically injured patients, and incorporate this into an IV catheter technology platform. Hematocrit measurement/diagnostic use in trauma, other surgical applications being explored. B-BIC image of external link icon Erin McKenna
Inhibition of CD40-TRAF signaling for the treatment of vascular inflammatory disorders Therapeutic Heart Our NCAI funded project is to develop an Inhibitor of CD40-TRAF signaling for the treatment of vascular inflammatory disorders.  The CD40 - CD154 pathway drives vascular inflammatory disorders and a broad variety of other diseases including neointima formation after arterial injury, atherosclerosis, allograft rejection, and ischemia/reperfusion induced tissue injury, inflammatory bowel disease, microvascular complications of diabetes, lupus, rheumatoid arthritis and other autoimmune diseases. Animal studies demonstrated that blockade of CD40 - CD154 interaction effectively controls vascular inflammatory disorders and various non-vascular inflammatory and autoimmune diseases. Moreover, clinical trials of CD40 blockade by administration of anti-CD154 mAb diminished disease activity in patients with lupus.  We have identified an inhibitor of CD40-TRAF signaling that diminishes inflammation. In this project, we plan to generate and test analogues of the lead compound to determine if they have improved ability to inhibit CD40-TRAF interaction and diminish pro-inflammatory responses in vitro. The most active compound will be tested in animal models relevant to major cardiovascular disorders in need of better treatment.   Vascular Inflammatory Disorders NCAI-CC image of external link icon Mark Low
Instrumented urethral catheter for distributed pressure and EMG measurements Diagnostic Device Urology To produce a robust and well-tested prototype instrumented catheter that simultaneously measures both bladder and urethra function, enabling differentiation between structural and neural problems and evaluation during clinically relevant provocative manoeuvres Urinary incontinence MN-REACH image of external link icon Amy Moore
Intracardiac MRI Ablation-Monitoring Catheter Device Heart To develop an intra-cardiac MR Imaging (ICMRI) catheter that will improve MRI image quality and reduce imaging time for EP therapeutic interventions. To support MR imaging and allow for EP ablation procedures to be performed under MR. B-BIC image of external link icon Erin McKenna
Intravenous probenecid as an inotrope for the treatment of acute decompensated heart failure Therapeutic Heart The goal of this project is further development of a reformulation of the generic drug probenecid into an intravenous formulation for the treatment as a safe and effective inotrope for patients with acutely decompensated heart failure. The current oral formulation has demonstrated significant inotropic properties in preclinical studies and in and patients with stable heart failure. The project plan is to obtain GMP quality IV formulation and to conduct stability and and small animal testing in preparation for an IND filing. Heart Failure NCAI-CC image of external link icon Mark Low
LTS: Lung Texture Score Tool Lung The project is to develop an efficient, objective, and quantifiable approach to chest CT image analysis using Lung Texture Scoring (LTS) scale.  Developed at the Ohio State University, the LTS scale is the result of clinical research conducted by the project's co-Principal Investigator.  Pulmonary function testing is currently the standard tool for objectively assessing lung disease severity in chronic parenchymal and alveolar lung diseases, such as pulmonary sarcoidosis. High-resolution chest CT imaging is very sensitive for detecting lung pathology, and unlike pulmonary function tests (PFTs), which are subject to variability (e.g. patient effort, technical laboratory methodology, different interpretive algorithms) chest CT of lung parenchyma results are a better indicator of lung state.  Current approaches to CT scan result interpretation are poorly standardized with radiologist qualitative bias (mainly due time-consuming volumetric tracing in identifying pathological features), making its clinical applications difficult when evaluating interstitial lung disease (ILD). At present, there is no convenient, well-standardized, radiologist-generated CT image analysis approach that provides a reliable quantitative assessment of lung disease. Intended to fill this gap, the proposed software tool is an efficient, objective, and quantifiable approach to chest CT image analysis using an OSU published and peer-reviewed LTS scale. Lung imaging NCAI-CC image of external link icon Mark Low
Lung Assist Device Device Lung Patients with acute lung failure who are refractory to mechanical ventilation have poor prognosis and utilize significant healthcare resources. Veno-venous Extra-Corporeal Membrane Oxygenation (vv-ECMO) is being increasingly used to salvage such patients, as accumulating data indicate that it is effective and may improve survival. However, the currently used vv-ECMO catheter has two major shortcomings that render it subject to positional changes and re-circulation of oxygenated blood, thereby affecting its efficiency. This project will develop a newly designed/improved catheter system for patients in respiratory failure in need of vv-ECMO. Acute Lung Failure UC CAI image of external link icon Emily Loughran
MicroRNA Antisense Therapeutics in Cardiometabolic Diseases Therapeutic Heart Project will continue development of antisense oligonucleotides directed against a master regulatory microRNA controlling lipid and energy homeostasis. The therapeutic has been shown to decrease fat accumulation and inflammation in mouse obesity models. As part of this project, novel oligos will be tested for efficacy in obesity and NASH mouse models. Cardiometabolic disorders and nonalcoholic steatohepatitis (NASH) B-BIC image of external link icon Ron Blackman
Minimally Invasive Tissue Engineering Therapies for Acute Airway Injury Therapeutic Device Lung This project will develop and evaluate two formulations of a matrix embedded cellular device for treatment of airway inhalation injury. The formulations would be developed and evaluated in vitro and for efficacy in large animal trials. Airway inhalation injury B-BIC image of external link icon Erin McKenna
MMG22, a potent analgesic for chronic inflammatory pain associated with metastic/primary bone cancer Small Molecule Drug Cancer To evaluate optimal routes of delivery of MMG22, a potent analgesic without tolerance Bone Cancer MN-REACH image of external link icon Amy Moore
Motion-activated system (MAS) to prevent chest tube clogging Device Blood Chest tubes are extensively used to drain blood after every cardiothoracic surgery procedure until bleeding stops. About 2.7 million cardiothoracic surgeries are performed in the United States each year, with two chest tubes used per case on average. Chest-tube complications are serious clinical and economic burdens. Patients with clogged tubes must undergo additional open-chest procedures, raising the average cost of care 55% (over $20,000 vs. non-complicated surgery).  In cases of blood drainage-related complications, length of stay is prolonged by ~5 days versus 1 to 2 days for standard in-patient hospitalization.  In this NCAI funded project we plan to develop a novel, motion activated system (MAS) that can be attached to the outside of a chest tube to prevent clot build-up and associated obstruction of chest tubes and to improve patients' recovery, outcomes, and hospitalization costs. The initial project development plan is to optimize the MAS device and to conduct a pilot clinical study to prove device readiness for assessment of patient's and clinical user's feedback from device application for further refinement or modifications. Thoracic surgery NCAI-CC image of external link icon Mark Low
MRI-compatible Voltage Device Tracking for Multimodality Electrophysiology Device Heart Refinement and testing of an EP catheter with Voltage Device Tracking (VDT) electrodes, an associated acquisition front-end, and signal-processing algorithms that will allow catheter use during MRI, thereby providing time-efficient and accurate incorporation of MRI data into the EP procedure workflow. Atrial Fibrillation (AF) and Ventricular Tachycardia (VT) B-BIC image of external link icon Paul Tessier
Nano-engineered, non-thrombolytic small diameter synthetic vascular grafts Device Heart We are developing non-thrombogenic small caliber synthetic vascular graft comprising nano-engineered surfaces. This development will allow us to significantly decrease complications associated with synthetic vascular grafts, thereby increasing patient quality of life, while at the same time contributing to a reduction in healthcare costs. Thrombosis UC CAI image of external link icon David Fung
Nanofiber Tissue Engineered Vascular Graft (TEVG) Using 3D Printing Technology Device Cardiovascular Tailor-made nanofiber Tissue Engineered Vascular Grafts created by utilizing pre-operative 3D imaging data combined with a computer aided design (CAD) model, 3D printing and nanofiber technology will result in dramatically improved patient care. The mold for the nanofiber scaffolds will be printed from the pre-surgery 3D imaging data combined with a computer aided design (CAD) model. The nanofiber scaffold will then be coated around this custom mold for the creation of a patient-specific TEVG. Congenital Single Ventricle Anomalies NCAI-CC image of external link icon Mark Low
Neuromodulatory Implant Device (NI) for the Treatment of Obstructive Device Sleep The goal of this project is to develop a prototype that includes a miniaturized, multi-channel nerve monitoring and stimulation system and an external remote control device, and then to test the system by implanting it in an anatomically pre-determined area of the hypoglossal nerve in three human subjects. Functionality of the system will be assessed via both periodic post implantation monitoring and chronic, unilateral stimulation of the hypoglossal nerve. Based on the results of the study, the next step will be to develop clinically representative components for use in a commercial-grade, chronic implantable stimulator system. Sleep Apnea NCAI-CC image of external link icon Mark Low
Noncrushable Pills for Prevention of Opioid Abuse Therapeutic Drug abuse Drugs like oxycodone are misused by crushing or liquefying pills for immediate dosage, causing a euphoria, which perpetuates abuse. Few robust abuse deterrent formulations are currently FDA approved. The proposed research prevents illegal use of such prescription drugs by encapsulating the drug within a biodegradable elastomer that is unable to be crushed or liquefied and will also be stable to microwaving and freezing, which many current formulations are not. The drug will only be released in the stomachs of patients who take the pills as intended. Prevention of illegal use of prescription drugs UC CAI image of external link icon Ben Dibling
Novel Anti-Inflamatory Drug Targeting NOX2 in Acute Lung Injury Therapeutic Lung Project to develop a novel class of anti-inflammatory drugs that specifically target neutrophil NOX2, to ameliorate lung damages by ALI/ARDS. The project focuses on further developing rationally designed p67phox small molecule inhibitors, NOX2-I, to improve drug-like properties that maximally inhibit organ damage related to inflammation in preclinical models of ALI. Acute Lung Injury, Acute Respiratory Distress Syndrome NCAI-CC image of external link icon Mark Low
Novel Approach for prevention of vein graft intimal hyperplasia Device Heart To fund a proof of concept large animal study to show that Photochemical Tissue Passivation (PTP) treated veins reduce intimal hyperplasia. These projects are considered too early to have well defined clinical indications. B-BIC image of external link icon Lesley Watts
Novel Approaches for Platelet Storage Other Blood Continue development of a platelet additive solution containing glycosidase inhibitors allowing cold storage preservation of platelets with low storage lesion and high survivability after transfusion. Project will use in vitro and in vivo analyses to optimize storage conditions and assess improved survival. Blood platelet storage B-BIC image of external link icon Ron Blackman
Novel Therapeutics for Difficult-to-Treat Breast Cancer Small Molecule Drug Cancer To develop drug candidates that inhibit tumor glycolysis while limiting toxic side effects to normal cells. Cancer MN-REACH image of external link icon Amy Moore
Optical platform for rapid high-throughput screening of cellular mechanotransduction Tool Heart The initiation and/or progression of numerous pathologies has been linked to the dysregulation of cellular mechanotransduction. These pathologies include arteriosclerosis, hypertension, cardiomyopathy, and asthma which are relevant to the mission of NHLBI. We aim to develop and deploy a novel high-throughput screening (HTS) technology, that is compatible with standard image cytometry based HTS platforms, to screen for the efficacy of compounds to modulate cellular mechanotransduction processes in 2D cell cultures. Our objective is to use our technology to identify drugs that display the ability to modulate mechanosignaling as opposed to biochemical activity alone. Arteriosclerosis, Hypertension UC CAI image of external link icon Alvin Viray
Oral solid dosage formulation of Cholera toxin B subunit Biologic Drug Gastroenterology This proposal aims to develop an orally available targeted treatment for ulcerative colitis (UC) that utilizes plant-made cholera toxin B subunit (CTBp) as the active ingredient. In an animal model, oral administration of CTBp in liquid form can mitigate UC by facilitating mucosal wound healing, but requires prior ingestion of a large volume of bicarbonate buffer to neutralize stomach acid. It is anticipated that the combination of CTBp's unique wound healing effect and the convenience of a solid dosage form will represent a highly desired "first-in-class" treatment with the potential to transform UC standard of care. Ulcerative Colitis UofL-ExCITE image of external link icon Paula Bates
Oral THU-decitabine, a novel non-cytotoxic epigenetic therapeutic Therapeutic Blood Project to formulate oral tetrahydrouridine (THU)-decitabine into a single dual release formulation that releases THU prior to decitabine. This dual release formulation would offer patients pharmaceutically rationalized, low burden, long-term, outpatient, non-cytotoxic, normal stem cell sparing, p53-independent treatment of Sickle Cell Disease and Myelodysplastic Syndrome. Sickle Cell Disease, Myelodysplastic Syndrome NCAI-CC image of external link icon Mark Low
Peripherally restricted cannabinoids for chronic pain Therapeutic Drug abuse Chronic pain represents a major socioeconomic and clinical challenge, in part because even the most efficacious of the currently available remedies are limited by their side effects. We developed synthetic peripherally-restricted cannabinoids (PRCBs) that don't cross the blood-brain barrier, thereby providing pain relief without the side effects associated with central nervous system (CNS) cannabinoid receptor activation. These PRCBs are the first in their class to exhibit potent and repeated suppression of chronic pain symptoms, without development of tolerance, and with a complete lack of CNS-mediated side effects. Their effectiveness was demonstrated in widely used rodent models of chronic pain induced by peripheral nerve injury, burn injury, or chemotherapeutic drugs, and in cancer pain, where PRCBs also showed anti-tumor properties. Clinical implementation of PRCBs for treatment of targeted patient populations could provide relief of their chronic pain and suffering without affecting mental acuity, motor coordination, or memory. This project aims to conduct several crucial investigational new drug enabling studies including FDA-compliant assessment of safety pharmacology & toxicology, as a prerequisite to clinical implementation of PRCBs. Chronic pain UC CAI image of external link icon Steven Huyn
Pharmacokinetics of multifunctional nanochelators in iron overload disorders Therapeutic Blood Project will develop ultrasmall nanoprobes coated with iron chelators that will harvest excess iron from tissues and plasma. The bound iron complex will be cleared by the kidneys and eliminated via urine. The objectives of the project are to identify an optimized nanoparticle formulation and characterize its therapeutic efficacy in rat models. Iron overload disorders B-BIC image of external link icon Paul Tessier
Portable Magnetic Resonance Device for the Pulmonary ICU Device Lung To demonstrate that absolute lung density can be measured during breath-holds and whiel subjects are freely breathing using a prototype magnetic resonance lung density monitor (MR-LDM). These projects are considered too early to have well defined clinical indications. B-BIC image of external link icon Lesley Watts
Preclinical and Clinical Studies of a Novel Read-Through Drug Capable of Restoring Cardiac and Muscle Function in Duchenne Patients Therapeutic Heart Duchenne muscular dystrophy (DMD) is the most severe of the neuromuscular disorders and affects 1 in 3500 newborn males. Approximately 13% of the mutations that cause DMD are nonsense mutations that lead to lack of dystrophin. The affects skeletal and cardiac muscles and is characterized by progressively loss of ambulation and premature death by cardiac or respiratory failure by the age of 30. Pulmonary symptoms also develop, such as shortness of breath and fluid accumulation or congestion in the lungs. This project will focus at developing and optimizing a drug capable of suppressing nonsense mutations and restore normal, full-length dystrophin expression. The same drug could also be used to treat virtually any genetic disease known to be caused by nonsense mutations (30% of the genetic disorders known to date). Duchenne muscular dystrophy UC CAI image of external link icon Steven Huyn
Rapid antimicrobial susceptibility testing from a colony (rapid AST) Diagnostic device Bacterial infection To develop a technology that enables rapid antimicrobial susceptibility testing from a colony in less than an hour. Bacterial Products MN-REACH image of external link icon Amy Moore
Rapid Perfusion Catheter Device Blood Refinement and testing of a novel catheter system that allows fast, easy insertion of a large diameter catheter in constricted vessels of hypovolemic patients for rapid infusion of IV fluids. Hypovolemic hypotensive shock B-BIC image of external link icon Paul Tessier
Reducing health-care utilization in pulmonary embolism Diagnostic Lung To develop an image analytic software platform to assess the vascular remodeling and heterogeneteity of the pulmonary vascular bed and its impact on cardiac remodeling with the ultimate goal to predict recurrence in patients suffering from PE. These projects are considered too early to have well defined clinical indications. B-BIC image of external link icon Lesley Watts
Reducing sepsis-related mortality in cancer patients through microbiome therapy Biologic Drug Sepsis To develop a rapid early diagnostic method to predict incidence of bloodstream infection in patients undergoing chemotherapy by evaluation of patient microbial DNA Sepsis MN-REACH image of external link icon Amy Moore
Selective targeting of TGF-b activation for airway remodeling with engineered monoclonal antibodies Therapeutic Respiratory Chronic obstructive pulmonary disease (COPD) is now the third leading cause of death in the United States (2) Current treatments provide incremental palliative benefit in COPD patients. There are currently no therapeutics which have been demonstrated to change the course of the disease. This project focuses on developing diagnostic and therapeutic antibodies which target TGFb mediated inflammation and fibrosis in COPD. These will be used to identify the sub-populations of COPD patients where modification of TGFb activation has the greatest potential impact and to develop a TGFb activation targeted therapeutic. Pulmonary diseases such as COPD and IPF UC CAI image of external link icon Debbie Alexander
Silencing airway nociceptors for treatment of cough and airway inflammation Therapeutic Lung Project will continue development of a novel class of permanently charged cationic sodium channel blockers for the treatment of cough. The project will pursue preclinical proof-of-concept efficacy and PK studies to advance lead candidates toward clinical development. Cough B-BIC image of external link icon Ron Blackman
SpheraHance, a Cancer-Targeted Contrast Agent for MRI and CT Imaging Contrast agent Cancer The product proposed is a cancer-targeted contrast agent with improved specificity for malignant vs. benign lesions and improved sensitivity. This product consists of gold nanoparticles (for CT contrast) coated with gadolinium (MRI contrast) and a cancer-targeting aptamer that causes particles to concentrate inside malignant cells. For detection, diagnosis, treatment planning, and monitoring of most types of cancer. UofL-ExCITE image of external link icon Paula Bates
Stem Cell-derived islets for treatment of type 1 diabetes Biologic Drug Diabetes Mellitus To demonstrate proof-of-concept of an encapsulated stem cell-derived islet product for treatment of diabetes Type 1 Diabetes Mellitus MN-REACH image of external link icon Amy Moore
Targeting Erythropoietin-based Therapeutics Therapeutic Blood Project will continue development of a safer erythropoiesis stimulating agent. Current treatments carry a black box warning because of undesirable thrombotic effects and more, due presumably to the on-target effects of erythropoietin (EPO) on non-RBC lineage cells. This project will study a modified EPO that is designed to avoid these detrimental effects. The therapeutic will be used in mouse model studies to assess its PK, PD and efficacy and prepare it for downstream development work in primates. Anemia B-BIC image of external link icon Ron Blackman
Technology for Diagnosis of Cystic Fibrosis in Two-Week-Old Newborns Diagnostic Lung The goal of this project is to develop an alpha prototype of a diagnostic device for testing for cystic fibrosis (CF) in newborns 2 weeks of age. The gold standard test for CF is the sweat chloride test which currently requires 15-75 microliter of sweat, however many infants younger than 3 months cannot produce this much sweat. Therefore a definitive diagnosis is not available until 3 months or later. At that time irreversible damage has already occurred, mainly to the pancreas, intestines, and most importantly, lungs. Our technology, based on unique and protected IP, makes it possible to accurately sample and analyze sweat 2 microliters in volume, which can be obtained at 2 weeks of age. Unique inventions in iontophoresis, micro-sampling, microanalysis, and control contribute to enable this performance. Cystic Fibrosis NCAI-CC image of external link icon Mark Low
Therapeutic Apheresis by Microfluidic Acoustic Separation Device Blood To develop an acoustic apheresis device that will meet or exceed the performance of traditional, centrifugal apheresis without detriment to blood health. Apheresis B-BIC image of external link icon Erin McKenna
Thiocaccharides as novel mucolytics for lung disease Therapeutic Lung This program is to develop a novel mucolytic treatment for mucus pathology in airway disease. Highly elastic mucus is difficult to clear and it results in airflow obstruction and airway infection, but there are currently no mucolytic drugs that can be given to patients by hand held inhaler. We recently discovered a mechanism of oxidant-induced increases in mucus elasticity that identifies excessive numbers of mucin disulfide bonds as a therapeutic target in stiff mucus gels. We are optimizing a series of inhaled mucolytics for Cystic Fibrosis, COPD and asthma. Mucus disease of the lung (Cystic Fibrosis, COPD, asthma) UC CAI image of external link icon Shikha Sharma
Treatment of vein graft disease by suppressing D114-Notch Signaling Therapeutic Heart To develop therapeutic anti-human D114 antibiodies, screen and test antibody candidates, and test the effects of the most efficient antibody in large animal models of vascular diseases. These projects are considered too early to have well defined clinical indications. B-BIC image of external link icon Lesley Watts
U of M Food and Nutrient Database API to Support mHealth, teleHealth and wearable Health Applications mHealth, teleHealth, wearableHealth Nutrition-related chronic diseases such as coronary heart disease, stroke, hypertension, diabetes, renal disease, and gastrointestinal conditions To create global access to the University of Minnesota Food and Nutrient Database? through development of an application programming interface (API) in order to meet software developer needs for a comprehensive, complete, up-to date, and reliable food and nutrient database to support patients living with nutrition-related chronic diseases. No disease or organ indication (platform technology) MN-REACH image of external link icon Amy Moore
Variable Stiffness Microcatheter for Navigation of Tortuous Vessels Therapeutic Device Heart To develop a steerable tip design microcatheter to improve endovascular navigation and reduce procedure time. To access distal, tortuous vasculature and support the controlled and selective infusion of diagnostic, embolic, or therapeutic materials into vessels. Potential for peripheral and neurovascular clinical indications. B-BIC image of external link icon Erin McKenna
VisiTube: Revolutionizing Chest Tube Insertion With Balloon Variable Rigidity, Real-Time Visual Guidance, and Advanced Anesthetic Management Device Lung Pleural chest tube placement performed routinely for fluid and/or air collection inside the chest can have significant complications and even result in patient deaths. This project will develop a video-guided device that provides physicians with visual aid during the chest tube insertion process, greatly reducing the risk of pneumothorax. Chest tube insertion UC CAI image of external link icon Emily Loughran
Shear Activated Nanothrombolytic Therapeutic Lung Project will continue development of a nanotechnology-enabled thrombolytic delivery system that targets drug selectively to sites of flow obstruction based on local increases in fluid shear stress, thereby focusing the drug activity at the site of the blood clot. This approach aims to reduce systemic exposure to free thrombolytic and minimize unwanted systemic side effects including bleeding and neurotoxicity. The project milestones include: (i) demonstration of enhanced clot dissolution in in vitro and in vivo models using nanoparticles produced by an optimized manufacturing protocol, and (ii) development of storage methods that maintain the active formulation in a stable form. Radial Artery Spasm B-BIC image of external link icon Ron Blackman
Novel Treatment for Long QT Syndrome Therapeutic Heart Project will continue development of a candidate series of compounds that will shorten the QT interval in a self-limiting fashion in patients with LQTS. The project will undertake a med chem program to identify lead candidates with preferred physiologic properties. The lead candidates will then be tested in a panel of newly generated iPSC-derived cardiomyocytes from LQTS patients of multiple etiologies. The aim is to have identified a Lead molecule that can used in IND-enabling studies. Long QT Syndrome B-BIC image of external link icon Ron Blackman
Development of an electroceutical for treatment of comorbidity between hypertension and major depression Therapeutic Device Heart Hypertension is a leading cause of morbidity and mortality in the United States with an overall prevalence of approximately 29%, corresponding to 70 million of Americans. Despite the benefits of existing blood pressure lowering drugs, 50% of hypertensive patients are inadequately controlled while taking medication and reduction in cardiovascular disease (CVD) incidence remains an important goal. A chronic withdrawal of vagal tone has been involved in treatment-resistance, structural cardiac remodeling and progression to CVD in hypertensive subjects, suggesting this marker as a potential novel therapeutic target. Hypertension is also frequently associated with major depression, with an estimated comorbidity of 22%. Patients with hypertension and comorbid depression are particularly prone to present cardiac vagal dysregulation, and have an increased risk for the development of CVD. Furthermore, this particular group of patients represents a challenge to physicians and healthcare providers who are unable to reach blood pressure target reductions with available antihypertensive medications, and need to consider cardiac adverse events and complicated cardiovascular prognosis with the use of some antidepressants. Hypertensive patients, and in particular those with comorbid depression, could greatly benefit from an intervention oriented to regulate vagal activity, with subsequent effects in blood pressure and cardiovascular risk reduction. Given preliminary work from our group, we are proposing the development and validation of an enhanced transcutaneous vagus nerve stimulation system by gating the stimulation to specific variations in respiratory and cardiac activity, which will optimize its effects in blood pressure reduction and cardiovascular autonomic modulation in hypertensive patients with comorbid depression. Hypertension B-BIC image of external link icon Erin McKenna
SQPAN Therapeutic Device Heart The field of the invention is systems and methods for cardiac electrical stimulation and electrocardiographic monitoring for autonomous device-based diagnostic and therapeutic decision-making. A method for a fully implantable, subcutaneous, powered, wireless, personal area network (PAN), or ?body bus?, for long-term, ambulatory, electrocardiographic surveillance using an array of physically independent but cooperating sensors, coupled with implanted devices that provide timed electrical stimulation, or pacing, to generate improvement in cardiac structure and function, is provided. Such electrical therapy systems may include multiple stimulation electrodes at various locations within and outside the cardiac surface in various combinations. The exemplary implementation addresses the controlled initiation and propagation of single or multiple opposing radial wavefronts generated by pacemaker stimulation and fused with spontaneous cardiac electrical activity to normalize electromechanical activation in heart failure, termed ?cardiac resynchronization therapy (CRT)?. The sum of these electrical waves is expressed as the body surface QRS complex, which is characterized and quantified using a novel method of wave interference superposition between 2 or more point sources (?fusion?). The autonomous, body-worn SQ PAN technology solution integrates near- and far-field human cardiac electrical wave recordings with computational firmware for subcutaneous electrocardiographic recording and analysis for QRS complex-based fusion titration during CRT. The subcutaneous short range wireless network uses low-power integrated circuits and physiologic signals to achieve a wireless body-worn electrocardiographic sensor network. The implanted sensors collect various physiological signals designated for therapy titration and clinical event prediction. The physically separate devices can automatically and quickly associate, or ?pair? electronically. B-BIC image of external link icon Erin McKenna
PR1P, an inhaled novel short peptide for emphysema Small Molecule Drug Lung Emphysema is a chronic progressive pulmonary disease characterized by destruction of alveoli leading to impaired lung function that threatens human health worldwide. Disease progression is due in part to dysregulation of the survival factor Vascular Endothelial Growth Factor (VEGF). Emphysema has no cure: there are no drugs to prevent disease progression or restore lung tissue to health. We recently designed a novel 12 amino-acid peptide, PR1P, that upregulates endogenous VEGF, and that based on recent preliminary data we hypothesize could be used in humans to treat emphysema. Here, we propose to carry out proof of principle testing in animal emphysema models. Emphysema B-BIC image of external link icon Ron Blackman
Molecular Imaging of Dysregulated Angiogenesis in Pulmonary Arterial Hypertension Diagnostic Device Lung Pulmonary arterial hypertension (PAH) is a disorder of elevated pulmonary vascular resistance characterized by progressive remodeling and obliteration of resistance-determining vessels of the pulmonary circulation. Despite current therapies, transplant-free survival following the diagnosis of PAH remains slightly better than 50% at 5 years, due primarily to right heart failure. Outcomes in PH could be improved with earlier diagnosis, and with deployment of therapies that directly target pulmonary vascular remodeling before irreversible changes have occurred. Here we describe a pre-clinical development program for a positron emission tomography (PET) molecular imaging diagnostic test for PAH. This strategy utilizes a radioisotope-conjugated (89-Zr) humanized monoclonal antibody directed against VEGF (bevacizumab) to detect abnormal angiogenic activity in the pulmonary vessels of individuals in the early stages of pulmonary vascular disease. The rationale is based on histopathologic evidence of disordered angiogenic activity in the affected vessels of human disease, and molecular and histologic data from animal models of PAH demonstrating dysregulated angiogenic signaling. Our molecular probe is retained avidly in remodeled small pulmonary arterioles and vascular lesions in a robust animal model of PAH, and binds avidly to vascular lesions in sectioned human lung tissues affected by PAH. This pre-clinical development program would advance the first molecular imaging agent specifically designed for the diagnosis and management of pulmonary vascular disease, and provide a technology which would enable non-invasive identification of disease at earlier stages to permit earlier intervention, and could help to identify treatments which have the ability to modify the natural history of disease. Pulmonary Arterial Hypertension B-BIC image of external link icon Erin McKenna
A plasma microRNA lab-on-a-chip assay with high specificity and sensitivity for colorectal neoplasm diagnosis and monitoring Diagnostic Cancer The envisioned product is a diagnostic platform based on magnetic micro-bead extraction and electrochemical detection of a clinically-proven, proprietary panel of 7 plasma miRNAs (Colo-miR) that is capable of distinguishing patients with colorectal cancer from patients without cancers with 90% sensitivity and 100% specificity as well as distinguish patients with colorectal polyps from individuals without polyps or cancers with 65% sensitivity and 95% specificity. Colorectal cancer UofL-ExCITE image of external link icon Paula Bates
An Immunogenicity and Partial Toxicity Test of Mutated Human Parvovirus B19 in Macaques to Generate a Vaccine to Prevent Aplastic Anemia in Congenital and Acquired Anemias and Bone Marrow Transplants Vaccine Viral We are producing mutated Virus-Like Particless and testing their immunogenicity and side effects in the only animal model that is suitable for B19 testing: the macaque monkey. If successful, we envision that the B19 vaccine would be given to high-risk populations (SCD and HS patients) during infancy to help prevent aplastic crisis. The use of the vaccine could eventually be expanded to the general population because B19 (like other viruses such as rubella and zika), though generally benign, can cause fetal death or defects, if a woman is infected during the first or second trimester of pregnancy, particularly during epidemics. Human Parvovirus B19 UofL-ExCITE image of external link icon Paula Bates
Adenosine Deaminase as a Novel Immunotherapeutic Agent for the Treatment of Cancer Therapeutic Cancer We propose to develop a cancer immunotherapy involving intratumoral administration of adenosine deaminase (ADA)?an enzyme that irreversibly converts adenosine into inosine, a non-immunosuppresive nucleoside. A pegylated version of bovine ADA, is already FDA-approved for use as an enzyme replacement therapy in children with ADA-associated severe combined immunodeficiency. We propose to perform preclinical studies in mice in order to determine the optimal dose/ schedule for PEG-ADA treatment and to confirm that PEG-ADA is synergistic with ICI treatment, and we propose to perform a human Phase I/II clinical trial of PEG-ADA in combination with an ICI (Pembrolizumab) in patients who have inoperable late stage malignant melanoma. Although the initial indication for PEG-ADA would likely be unresectable malignant melanoma, it is potentially useful in many additional cancers types (e.g. non-small cell lung cancer, renal cell carcinoma, bladder cancer, and prostate cancer Melanoma UofL-ExCITE image of external link icon Paula Bates
Non-invasive real-time assessment of coronary stenosis using RBCAGE Diagnostic Cardiovascular Our technology provides an accurate, highly sensitive, non-invasive method to assess the significance of coronary stenosis through coronary angiography without i-FFR measurement. When performed in real-time, this allows the cardiologist to make an informed decision regarding stent placement. Notably, such a method would deliver the benefits of i-FFR measurement in terms of cost savings and improvement in patient outcomes, while simultaneously avoiding the disadvantages such as extra cost for the procedure and time burden. These funds will be used to: fully develop a correlation between our RBCAGE and i-FFR by conducting a retrospective study in 50-100 patients with known CAD who have already undergone coronary angiography & i-FFR; achieve real time processing; and develop dedicated software that integrates rendering and modeling with a user friendly interface to be used in future prospective studies. Coronary stenosis UofL-ExCITE image of external link icon Paula Bates
Avaren-Fc lectibody for liver graft protection against hepatitis C virus reinfection Therapeutic Virus The goal of this project is to develop a new biologic drug for liver transplant recipients with chronic hepatitis C virus (HCV) infection. Our solution is a chimeric antibody-like antiviral protein, Avaren-Fc lectibody, which would be infused during and after LT so that the graft liver is protected from HCV. Additionally, unlike other similar products under clinical development, Avaren-Fc lectibody is efficiently bioproduced in plants and exhibits potent inhibitory activity against HIV and cancer cells, in addition to HCV. Hence, if the safety and efficacy of Avaren-Fc is demonstrated for the proposed use, the product may also offer a new treatment option for HIV/HCV co-infection. To facilitate the preclinical development of Avaren-Fc lectibody, this two-year project will perform basic safety and efficacy studies in preclinical rodent models in collaboration with qualified contract research organizations. Hepatitis C UofL-ExCITE image of external link icon Paula Bates
Development of carbapenemase detection test Diagnostic Bacterial We have developed a test which rapidly detects gram-negative superbugs. The most dangerous superbugs produce a carbapenemase enzyme which inactivates carbapenems (drugs of last resort) and related antibiotics. Antibiotic resistance UofL-ExCITE image of external link icon Paula Bates