Abstracts

University of Missouri

Antiviral Compounds for the Treatment of Coronaviruses Such as SARS, MERS and MHV

The current invention developed at MU presents a unique technology for the treatment of coronavirus infections, for which there are currently no approved treatments. This technology involves a new class of enzyme inhibitors of coronavirus replication that block the helicase activity of a specific region of the virus. These helicase inhibitors block the nucleic acid unwinding activity of the virus to prevent the spread of viral infection. Coronaviruses, such as Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS) and related viruses present the real possibility of future outbreaks based on past coronavirus epidemics.

Coronaviruses are a group of RNA viruses responsible for illnesses ranging from the common cold to deadly infections. SARS is a highly contagious and sometimes life-threatening infection caused by the SARS-CoV coronavirus. MERS is a severe acute respiratory illness that is caused by the MERS-CoV coronavirus. Both of these illnesses carry high mortality rates and currently have no approved treatments or vaccines. Coronaviruses, such as the type that causes Mouse Hepatitis Virus (MHV), also affect animals and frequently result in death. The current technology presents novel antiviral compounds for the treatment of these previously untreatable viral infections.

Potential Areas of Application
  • SARS, MERS and MHV antiviral
  • Broad spectrum antiviral against many other coronaviruses
Patent Status

Patent issued

Inventor(s)

Stefan G. Sarafianos, Adeyemi O. Adedeji and Kamlendra Singh

Contact Info

Samuel E. Bish, bishs@missouri.edu or 573-882-5016; Nancy Parker, parkern@missouri.edu or 573-884-3553

Constrained Prosthetic Acetabulum

Dislocations can be a painful and expensive outcome after artificial hip replacement. This inventive prosthetic is a constrained ball-and–socket joint and is designed to prevent dislocations. The prosthetic consists of a D-shaped femoral head with the flat surface capable of attaching to any commercially-available femoral stem, a concave cavity liner that is slightly more than a hemisphere, i.e. the edges extend beyond the equatorial plane and a shell cavity is compatible to the liner.

The device’s unique liner design allows for the femoral head to be inserted at a particular alignment and rotationally constrained within the liner. In essence, the ball is keyed into the socket by virtue of its unique design and, much like a key in a door lock, any rotation of the head away from the point of insertion creates inherent stability in the construct, precluding component dislocation.

Potential Areas of Application
  • Hip replacement
Patent Status

Patent pending

Inventor(s)

Sonny Bal, Mohamed Rahaman and Mitch Tarka

Contact Info

Charlie Hanford, hanfordc@missouri.edu or 573-882-0477

Device and Technique for Tibial Plateau Allografting With or Without Attached Meniscus

This invention, developed by MU researchers, is a unique surgical instrumentation system that allows for standardized preparation of a tibial allograft from donor tissue with precisely matched preparation of the patient’s proximal tibia to receive a meniscal-tibial plateau allograft. This technology has the potential to revolutionize knee surgery by allowing for biological joint replacement of this difficult-to-treat region of the knee, increasing the use of organ donor tissue and improving outcomes for patients with this common knee problem.

Currently, patients with extensive damage to their tibial articular cartilage and/or meniscus in the knee have few treatment options that allow them to return to highly functional activities. Current standard-of-care allograft cartilage and meniscus transplantation techniques do not address these types of extensive injuries due to limitations in surgical site access, effective instrumentation and stabilization of viable and functional tissues. Complications arising from graft functionality, placement, and fixation to the tibia (as well as functionality of the underlying tibial cartilage) also inhibit success of current methods. Total and partial joint replacements using synthetic materials also do not allow return to these activities and have a limited functional lifespan. Younger, active patients want better options as surgeons search for biological treatments that consistently provide them with more optimal outcomes. MU’s technological advancement has the potential to address all of these limitations.

Potential Areas of Application
  • Human orthopaedic surgery
  • Veterinary medicine – orthopaedic surgery
Patent Status

Patents pending

Inventor(s)

Ferris Pfeiffer, James L. Cook and James P. Stannard

Contact Info

Samuel E. Bish, bishs@missouri.edu or 573-882-5016; Nancy Parker, parkern@missouri.edu or 573-884-3553

Device to Assist Delivery of the Well-Applied Fetal Head at Cesarean Section

Caesarean sections are the most common major operation performed in the U.S. and the industrialized world. Arrest disorders affect up to 20 percent of labors and are the most common indication. Between 100,000 to 400,000 of the deliveries can be complicated by a strong seal formed between the fetal head and the lower uterine segment (“well-applied” fetal head) during the second stage of labor. The breaking of such a seal is difficult, requires additional procedures, presents risk to the fetus and can introduce vaginal bacteria into the patient’s uterine cavity.

This invention is a novel obstetric device designed to assist in the delivery of the “well-applied” fetal head during caesarean section. The device is crafted of sterile, pliable material designed to allow a surgical assistant to easily and comfortably palpate the fetal head and break the suction between the head and the lower uterine segment. The device decreases the force needed to facilitate delivery and reduces potential trauma to the mother and fetus.

Potential Areas of Application
  • Caesarean section delivery
Patent Status

Patents issued and FDA-approved

Inventor(s)

Breton F. Barrier and Gary F. Clark

Contact Info

Charlie Hanford, hanfordc@missouri.edu or 573-882-0477

Dual Colorimetric-Fluorescent Sensor for Early Detection of Diabetic Retinopathy: DR-Sensor

Diabetic retinopathy (DR) is a major micro-angiopathic complication that arises in both Type 1 and Type 2 diabetic patients. According to International Diabetes Federation (IDF) 2013 statistics, nearly 8.3 percent of adults (382 million people) have diabetes, and that number is expected to exceed 592 million in less than 25 years. DR damages the blood vessels in the retina resulting in vision loss or blindness. In fact, DR is considered a major cause of blindness in both Indian and American adult populations. The prevalence of DR shows large variations globally.

Depending on the severity of the disease, DR is classified in four stages: mild, moderate, severe and proliferative retinopathy. Although the complications are overwhelming, patients even in an advanced stage of DR often show no symptoms. Vision loss is preventable by timely detection and treatment; therefore, diabetic patients are required to have frequent eye exams.

A typical eye exam in diabetic patients includes a visual acuity test, a dilated eye exam and tonometry. These tests are expensive and time-consuming. An in-home sensor could solve this problem, but developing a sensor requires a validated biomarker that needs to be secreted by urine, or other body fluids. A simple nanotechnology-based sensor for in-home applications will help in early detection of diabetic retinopathy patients and help prevent vision loss for diabetics.

MU researchers have developed an in-home sensor for early detection of diabetic retinopathy. It features a test strip onto which a sample of urine is placed, and a positive test result is indicated by the appearance of a fluorescent red color on the test portion when exposed to a hand-held UV light source. Results are obtained in less than 10 minutes.

Potential Areas of Application
  • Early detection of diabetic retinopathy
Patent Status

Patent pending

Inventor(s)

Raghuraman Kannan, Sandhya Saranathan, Anandhi Upendran and Uzma Khan

Contact Info

Charlie Hanford, hanfordc@missouri.edu or 573-882-0477

Electrocardiogram (ECG) Biomarkers for Pre-Symptom Detection of Infectious Diseases

This invention from MU uses electrocardiogram (ECG) to identify intervals in an individual’s heart rhythm as biomarkers for pneumonic plague and other infectious diseases. Device applications of this ECG biomarker technology can be used to identify exposure to infectious agents befoe the onset of detectable disease symptoms. This technology also has the potential to identify ECG biomarkers that can correlate responses of protective and non-protective therapeutic treatments.

Traditional methods of testing for pathogens and other infectious agents can take up to 72 hours to obtain reliable results. More rapid methods of detection are needed to combat fast disease progression and transmission of the infection. Currently available methods for rapid detection of pathogens include various kinds of PCR that involve expensive DNA extractions and sometimes the inability to confirm bacterial viability in the test sample. Therefore, implementing a more cost effective and rapid method to detect exposure to infection before the onset of symptoms would enable more timely and effective treatment of affected individuals.

Potential Areas of Application
  • Non-invasive and efficient hardware and software applications to identify oncoming and progressing infectious diseases
  • Wearable bio-warfare technology for military to detect exposure to infectious agents
  • Evaluate the success of various therapies for infectious diseases during the course of treatment
Patent Status

Patent pending

Inventor(s)

Deborah Anderson, Eric Coate, Miqdad Dhariwala and Joshua Willix

Contact Info

Samuel E. Bish, bishs@missouri.edu or 573-882-5016; Nancy Parker, parkern@missouri.edu or 573-884-3553

Element 1 Antisense Morpholinos Gene Therapy

Spinal Muscular Atrophy (SMA) is a lethal genetic disease in infants that causes degeneration of SMN protein in the spinal cord. In humans, SMN protein is produced by a gene called Survival Motor Neuron 1 (SMN1). Loss of the SMN1 gene in newborns leads to the development of SMA and ultimately death. An identical gene to SMN1 – known as Survival Motor Neuron 2 (SMN2) – is expressed in humans, but can only make a fraction of SMN protein. SMN2 lacks a final coding exon (exon 7) that permits SMN1 to create an abundant amount of SMN protein. However, infants with SMA retain a copy of SMN2, thereby making an ideal target to modulate its splicing patterns and produce more SMN protein.

The current invention developed by MU researchers uses morpholino chemistry to create an SMN2-specific antisense oligonucleotide (ASO). This antisense oligonucleotide anneals to a repressor region of SMN2 exon 7 called Element 1 (E1). Uninhibited E1 activity leads to the reduced production of SMN protein by the SMN2 gene. The antisense oligonucleotide blocks E1 repressive activity and allows the SMN2 gene to express large amounts of SMN protein. This gene therapy can help replenish the defect
of SMN protein seen in infants with the disease.

Potential Areas of Application
  • Pharmaceutical companies developing SMA-specific therapies
Patent Status

Patents pending

Inventor(s)

Christian Lorson and Erkan Osman

Contact Info

Samuel E. Bish, bishs@missouri.edu or 573-882-5016; Nancy Parker, parkern@missouri.edu or 573-884-3553

Gold Nano Rod-Based Diagnostic Platform

Gold Nano Rod HistoChemistry (GNR-HC) is a platform technology. The technology can be extended to biomarkers of interest in cancers and other pathologies by careful variation of the biomolecule attached with the nanoparticles. In addition to histochemical detection of tissue proteins, this methodology also has the capacity to identify RNA and DNA in situ.

MU’s team has applied GNR-HC for identifying and quantifying EGFR-expression (EGFR-Sure) and c-MET expression (cMET-Sure) in a human tissue sample. The technology employs a synthetic biomolecule that is anchored to gold nanorods. The biomolecule is highly selective for binding to the targeted protein, and the gold nanorods provide a unique imaging agent. The combination of gold nanorods with bound ligands specific for binding to EGFR provides a simple “stain” that quickly allows a histologist to determine if a tumor is over-expressing EGFR. The use of a metal nanoparticle provides a reproducible intensity that will not diminish with repeated observation allowing repeat cataloging of results. In addition, the technique is highly specific, cost-effective and user-friendly.

Potential Areas of Application
  • Tumor analysis and diagnosis of other diseases
Patent Status

Patent pending

Inventor(s)

Raghuraman Kannan, Mythili Ramachandran, Charles W. Caldwell, Charles W. Caldwell, Jr., Nripen Chanda, Ajit Prakash Zambre and Gerald Arthur

Contact Info

Charlie Hanford, hanfordc@missouri.edu or 573-882-0477

Hybrid Synthetic Biologic Joint Arthroplasty Systems

The current invention developed by MU researchers comprises a group of related implants, instruments and techniques that provide a variety of options for performing joint replacement and resurfacing surgeries. The implants will be composed of a synthetic component and a biologic component. The hybrid implants are designed to optimize long-term success in joint replacement and resurfacing surgery of all major joints by combining the advantages of synthetic and biologic arthroplasty techniques while minimizing the disadvantages of each.
The demand for joint replacement surgeries is expected to rise exponentially in the coming years, based on rising elderly populations and an increase in a sedentary lifestyle in the United States. However, existing methods of implanting joint replacements are not capable of measuring forces from a variety of real-life impact situations and cannot be tailored to an individual patient’s needs.

Potential Areas of Application
  • Treatment for focal cartilage defects of the knee, ankle, elbow and shoulder
  • Partial and complete hemi-arthroplasties for trauma or arthritis
  • Total joint arthroplasty of the knee, shoulder, hip, ankle, elbow, wrist, TMJ, fingers and toes for trauma and/or arthritis
Patent Status

Patents issued and pending

Inventor(s)

James L. Cook, Clark T. Hung, Gerard Ateshian, Eric Lima and Li Ming Bian

Contact Info

Samuel E. Bish, bishs@missouri.edu or 573-882-5016; Nancy Parker, parkern@missouri.edu or 573-884-3553

Improved Dual Gold-Iron Alloy Nanoparticle Conjugates for Selective Separation of Globin or Trophoblast Cells From Biological Matter and Methods

Based on the current available technique, the inventors have developed a method for selective isolation of globin or trophoblast cells from biological matter using core-shell magnetic nanoparticles containing multiple copies of antibodies on the surface. The selective separation is based on antigen-antibody interaction of nanoparticles. The material used for separation contains multiple copies of a selected antibody on the surface with high affinity toward a chosen antigen of interest.

Globin or trophoblast cells separated from the biological matter retain structural and biological identity and are therefore ready to be investigated by conventional analytical techniques.

The method described for selective separation and enrichment of analyte is adequate for subsequent analysis. The separation of globin from the feces enables early detection of colorectal cancer. In similar fashion, separation of trophoblast cells obtained from a vaginal swab (or other biological matter) aid in subsequent genetic analysis of cells for predicting the health of a baby.

Potential Areas of Application
  • Separation of globin for analysis
  • Separation of trophoblast cells for analysis
Patent Status

Patent pending

Inventor(s)

Raghuraman Kannan, Sandhya Saranathan, Anandhi Upendran and Shreya Ghoshdastidar

Contact Info

Charlie Hanford, hanfordc@missouri.edu or 573-882-0477

Instrument to Close Fascia During Laparoscopic Surgery

After a laparoscopic surgery procedure, a surgeon must often accurately close a trocar port site in the anterior abdominal wall following removal of a large trocar cannula from the port site. Failure to close the site, or an improper closure of the port site can sometimes lead to a herniation of the bowel and subsequent bowel obstruction. Because the standard closure technique for the trocar port site is through a small incision, the present mode for closure of a trocar port site is to reach down to the desired tissue layer with pickups and a loaded needle driver to grasp the needle through the abdominal wall and withdraw the needle with the pickups to secure a stitch across the port site. Many times the skin incisions must be extended to accomplish suturing the port site closed.

This surgical instrument can be introduced through a current trocar puncture site. Using a “pitch and catch” mechanism, the device places a suture in the deep fascia and peritoneum of the anterior abdominal wall, reducing needle sticks and resulting in a more complete closure of the site. It is a lightweight and easy-to-use instrument that can be operated quickly and efficiently to close a trocar puncture wound in a simple and economical manner.

Potential Areas of Application
  • Laparoscopic surgery closures
Patent Status

Patent pending

Inventor(s)

Jaya Ghosh, Ellie Koehly, Yaw Sarpong and Roger de la Torre

Contact Info

Charlie Hanford, hanfordc@missouri.edu or 573-882-0477

Nano-Ayurvedic Medicine Through Green Nanotechnology-Production of Gold Nanoparticles Using Traditional Ayurvedic Principles

Ayurvedic medicine is an ancient healing modality originating in India about 5,000 years ago. This is the oldest medical system in the world, advocating holistic medicine principles aimed at achieving prevention and curative therapies to restore balance in the human body to prevent long-term illness and to promote natural wellness. In most countries, across the world, Ayurveda medicine is still considered to be an "alternative" medical modality. However, in the United States, Japan and Germany and in many other countries, Ayurveda is gaining prominence because of its inherent power of providing a healing mechanism addressing the entire body to treat diseases by identifying primary causes of illness — all with minimal or no toxic side effects.

Globally, Ayurvedic medicine has penetrated less than 2 percent of the population, suggesting an unprecedented growth potential for this important medical modality. Ayurveda medicines are always administered in combination with a plethora of herbs, metals and metal ions (in the form of ash or referred to as “Bhasma” in the Ayurvedic literature). Gold ash, mixed with a cocktail of herbs, has been extensively used in the treatment of cancer, arthritis (both osteo and rheumatoid), various infectious diseases and also in opening-up blocked arteries in cardiovascular therapy. Gold ash formulations are also used in treating various neurological disorders.

The undefined chemical formulations of gold ash have always resulted in irreproducible chemical species causing high unpredictability in administering the well-defined active ingredient through scientifically acceptable measured doses. These challenges have often resulted in high toxicity of metallic species, or sometimes less than optimal bioavailability of biologically active species – all causing significant challenges for wider acceptability by regulatory agencies such as the U.S./European FDAs.

This invention reports on the discovery of herbally-initiated, green nanotechnology-derived, production of gold nanoparticles using strict 'Ayurvedic Principles' (without the use of any toxic or man-made chemical). The process is 100 percent reproducible, and scale up for commercial production has also been achieved, thus paving the way for the rapid expansion and wider acceptability of the field of Ayurvedic medicine through our new approach referred to as ‘Nano-Ayurvedic Medicine.’ Our green nanotechnology approaches will rejuvenate Ayurveda medicine in order to provide universally acceptable medical standards for launching a series of Ayurnano products for treating a myriad of human diseases and disorders.

Potential Areas of Application
  • Cancer therapy
  • Arthritis
Patent Status

Patent pending

Inventor(s)

Kattesh Katti, Menka Khhobchandani, Kavita Katti, Chintamani Joshi and Vinay Mutalik

Contact Info

Charlie Hanford, hanfordc@missouri.edu or 573-882-0477

New Surgical Tools and Techniques to Make Patient Anatomy-Specific Osteochondral Grafts Possible

The current invention developed by MU researchers includes the surgical instrumentation and method for creating custom anatomic osteochondral allografts (OCA), or autografts to treat damaged areas of joints. The revolutionary instrumentation allows for contouring of grafts to the patient’s anatomy and precise preparation of the recipient site for an OCA (or autograft of complex geometry), rather than simple cylindrical grafts as currently performed.

Between 600,000 and 900,000 patients in the U.S. undergo surgical treatment for articular defects resulting from osteochondritis dessicans, injury, trauma and osteoarthritis. Currently, surgeries using OCA (or autograft) comprise a small portion of the total number of procedures performed to treat these conditions due to their limitations. Though current allografts/autograft techniques are relatively easy to perform, they are not optimal for treating large articular defects in joints with complex geometries. The use of cylindrical grafts for these types of joint damage results in sub-optimal use of donor tissues, inability for anatomic reconstruction of defects, comprised graft stability and removal of significant amounts of healthy cartilage to replace all damaged tissue. All of these downfalls can lead to unsuccessful outcomes for patients, such as graft failures and disease progression, mainly due to the function of the non-patient-specific geometry of a standard cylindrical OCA (or autograft). MU’s technology is predicted to overcome current OCA and autograft procedural pitfalls to improve outcomes and increase the number of patients who can be effectively treated with OCA and autografts.

Potential Areas of Application
  • Human or veterinary orthopaedic surgery (treating focal cartilage defects in joints)
Patent Status

Patent pending

Inventor(s)

Ferris Pfeiffer, James L. Cook and James P. Stannard

Contact Info

Samuel E. Bish, bishs@missouri.edu or 573-882-5016; Nancy Parker, parkern@missouri.edu or 573-884-3553

Novel Nano-Graft Designed to Improve the Efficacy of ACL Reconstruction

An anterior cruciate ligament (ACL) is one of the most commonly injured ligaments of the knee. A current problem experienced by many ACL-reconstruction patients is joint instability caused in part by lack of cellular integration and remodeling, leading to deterioration of the graft. Thus, there is a critical need for a new graft material that promotes cellularity, integration and recapitulation of natural joint function. This new nano-graft may provide joint stability in ways superior to existing grafts for soft tissue repair.

MU’s team has developed a patented technology where nanomaterials are conjugated to a cellular tissue. The nanomaterials provide a 3-D tissue network that has enhanced remodeling and controlled degradation. In addition, the innovative material promotes cellular in-growth and provides good mechanical behavior, which will improve with time due to the recapitulation of tissue and ligament remodeling. The transformative technology uses a functionally graded nano-graft. The nano-graft material is a platform technology.

Potential Areas of Application
  • ACL reconstruction
  • PCL and MCL reconstruction
  • Soft tissue replacement, such as rotator cuffs
  • Achilles, patellar, quadriceps and biceps tendons
Patent Status

Patent pending

Inventor(s)

Sheila Grant, David Grant, Richard White, Sharon Bachman, Daniel Grant and Matthew Cozad

Contact Info

Charlie Hanford, hanfordc@missouri.edu or 573-882-0477

Novel Sodium Channel Blockers

A new family of voltage-gated sodium channel blockers has been synthesized that potentially provides therapeutic alternatives to currently used analgesics, antiarrhythmics, anticonvulsants and antidepressants. The sodium channel is an integral part of nerve and cardiac cell conduction pathways. The small, structurally unique sodium channel blockers described here differ from current sodium channel blockers such as lidocaine. Preliminary studies of the physiology and neurobehavior of these compounds show that they are functional sodium channel blockers. In cell expression studies these compounds block brain type sodium channels in a manner typical of local anesthetics. These compounds provide analgesia after sciatic nerve injection and have a longer duration of action than lidocaine in vivo. Importantly, their unique structures make them poised to show selectivity among sodium channel subtypes in excitable cells.

Potential Areas of Application
  • Inflammatory and neuropathic pain
  • Abnormal cardiac rhythms
  • Depression
  • Seizures
Patent Status

Patent issued and pending

Inventor(s)

George R. Kracke, Yulia Sevryugina and M. Frederick Hawthorne

Contact Info

Charlie Hanford, hanfordc@missouri.edu or 573-882-0477

Novel Dystrophin Membrane-Binding Domains (MBDs)

Duchenne muscular dystrophy is a lethal muscle-wasting disease caused by mutations in the dystrophin gene. Dystrophin plays an important role in maintaining the integrity of the sarcolemma (muscle cell membrane). Lack of functional dystrophin leads to membrane leakage and disruption. Damage of the muscle membrane initiates chain reaction that eventually ends up in muscle necrosis, fibrosis, inflammation and loss of muscle function.

Traditionally, dystrophin is divided into four functional domains: N-terminus (NT), the mid-rod domain, the cysteine-rich (CR) domain and C-terminus (CT). The mid-rod domain consists of 24 spectrin-like repeats (R) and four hinge regions (H). Dystrophin is a subsarcolemmal protein. It maintains sarcolemmal integrity by providing a mechanical and signaling link between the actin cytoskeleton and the extracellular matrix {ECM}. A critical aspect of this link is the direct interaction of dystrophin with the muscle cell membrane. The prevailing theory suggests that the CR domain anchors dystrophin to the sarcolemma through direct binding to the trans-membrane protein β-dystroglycan. Β-dystroglycan then connects with the ECM. In this model, the CR domain is the sole component of dystrophin that can bind to the muscle membrane.

Membrane binding is essential for dystrophin to maintain membrane integrity. In this work, novel synthetic dystrophins were developed that bound dystrophin independently of the CR domain. This has important therapeutic implications, potentially allowing for new novel synthetic dystrophins with superior function for the treatment of muscular dystrophy.

Potential Areas of Application
  • Muscular Dystrophy
  • Duchenne Muscular Dystrophy
Patent Status

Patent pending

Inventor(s)

Dongsheng Duan, Yi Lai, Junling Zhao and Yongping Yue

Contact Info

Charlie Hanford, hanfordc@missouri.edu or 573-882-0477

Optical Polarization Tractography: A New High-Resolution Imaging Technology for Early Detection of Diseased Tissues

The current invention from MU uses non-destructive optical polarization tractography (OPT) to generate high-resolution, 3-D images of tissue fiber organization from cellular to organ levels. This technology can be used in clinical diagnosis to identify various abnormal and diseased tissues of various types, such as skeletal muscle, nerve fiber, dental tissue, cartilage, heart muscle and blood vessel. The technology is portable, low-cost to implement and can identify fiber disorganization/damage in skeletal and cardiac muscle for early detection of heart diseases and other tissue fiber abnormalities.

Current tissue imaging technologies, such as optical coherence tomography (OCT), cannot provide accurate images of the fiber architecture in fibrous tissues. Changes to the fibrous structure of various biological tissues generally occur under disease or pathological conditions, such as the onset and progression of heart failure or atherosclerosis. Cellular level fiber architecture changes are excellent biomarkers for early disease diagnosis and for monitoring disease progression and response to therapy. Unfortunately, current tissue imaging technologies do not have the resolution to detect fiber organization changes at the cellular level. The current invention of OPT technology represents a revolutionary advancement in tissue imaging technology that can improve our understanding of pathogenesis, monitoring of progression of disease conditions and assist in treatment modalities by offering unique imaging capabilities, such as detailed 3-D tissue visualization with cellular resolution.

Potential Areas of Application
  • An effective, low-cost, portable imaging tool to reveal tissue fiber abnormalities in skeletal muscles, nerve fibers, dental tissue, cartilage, heart muscles and blood vessels
  • Provide more detailed images of complicated tissues by offering 3-D capabilities, high imaging speed and cellular-level spatial resolution
Patent Status

Patent pending

Inventor(s)

Gang Yao, Dongsheng Duan and Yuanbo Wang

Contact Info

Samuel E. Bish, bishs@missouri.edu or 573-882-5016; Nancy Parker, parkern@missouri.edu or 573-884-3553

Osteoarthritis Biomarker Panel

Osteoarthritis (OA) is the most common form of arthritis in humans and affects almost 10 percent of the population in the U.S. and Europe. Currently, there is no commercially available assay(s) for diagnosis, staging or monitoring of the disease. The most common clinical approach uses physical examination and radiographic (X-ray) findings for evaluation of subjects that are exhibiting symptoms. This approach results in osteoarthritis being definitively diagnosed after it has significantly impaired function and quality of life. At this point, therapeutic options may be less efficacious.

The current invention developed by MU researchers is a human biomarker panel that may be useful for determining presence, severity and extent of OA. The panel uses readily available fluid samples, which are analyzed for specific biomarkers associated with OA. By comparing the levels of biomarkers in the fluid samples to normal values, the panels will allow for diagnosis, screening, staging and judging of the effectiveness of treatments with high certainty.

Potential Areas of Application
  • In-clinic tests for diagnosis, screening, staging, treatment monitoring and prognostication of OA
Patent Status

Patents issued and pending

Inventor(s)

James L. Cook, Aaron M. Stoker, Keiichi Kuroki, Bridget Garner, Cristi Reeves Cook, Richard Evans, Brandon Roller and Prakash Jayabalan

Contact Info

Samuel E. Bish, bishs@missouri.edu or 573-882-5016; Nancy Parker, parkern@missouri.edu or 573-884-3553

Osteochondral Allografts for the Ankle

The current invention from MU is directed to the development of viable osteochondral allografts for functional biologic ankle joint replacement in patients with severe ankle trauma and/or arthritis. The invention is a surgical instrumentation system for creating allograft implants and recipient graft sites with a precise fit for joint movement. This technology should replace current standard-of-care salvage procedures for ankle injuries and arthritis, such as ankle fusion, to return patients to pain-free, highly functional activity.

The ankle joint is the most commonly injured joint in the body. Ankle fractures occur in cases of high-energy trauma, such as motor vehicle, extreme sports and cycling accidents, and those of low-energy trauma, such as falls, athletic events and other repetitive impact activities. Patients with ankle arthritis are usually younger than those with knee or hip osteoarthritis. The longer projected life span, combined with the substantial decrease in health-related quality of life, underscores the profound effect that ankle trauma and osteoarthritis have on patient disability. Total ankle replacements using metal and plastic implants have not resulted in consistently successful outcomes, and the alternatives of ankle fusion or amputation are not functional alternatives. Given the available options, the current invention provides a new and attractive system for treating ankle arthritis and traumatic injury.

Potential Areas of Application
  • Demonstrates novel method to address ankle trauma and arthritis with a higher predicted probability of surgical success for functional outcomes
Patent Status

Under evaluation

Inventor(s)

Ferris M. Pfeiffer, James L. Cook and James P. Stannard

Contact Info

Samuel E. Bish, bishs@missouri.edu or 573-882-5016; Nancy Parker, parkern@missouri.edu or 573-884-3553

Shell Cutter Instrumentation for Patient-Specific Osteochondral Allografts

The current invention developed at MU presents a system to create a recipient site in a patient’s joint and matching osteochondral allograft (OCA) of a shape, contour and thickness specific to the joint for allograft transplantation. This technology uses surgical guides made from medical-grade materials that contours to the patient’s joint surface(s) to create an anatomy-specific recipient site, followed by instrumentation of the donor tissue to create a precisely matched OCA for transplantation. Most current OCA instrumentation systems do not allow for patient-specific implants, but MU’s shell cutter system allows the donor tissue to be created in an anatomy-specific shape, precisely matched to the recipient site for more complete joint restoration. MU’s technology presents a more accurate joint geometry and improved function compared to OCA instrumentation systems that are not patient-specific.

OCA transplantation is a proven and growing orthopedic procedure for patients needing restoration of the articular surfaces of joints. Organ donor tissues from accredited tissue banks are used to create allografts for transplantation into the recipient site(s) in patients. MU’s shell cutter system improves this method of treatment.

Potential Areas of Application
  • Treatment of damaged joint surfaces in the knee, hip, ankle, shoulder and elbow of human and veterinary patients
  • Alternative to partial or total joint arthroplasty options
Patent Status

Under evaluation

Inventor(s)

James L. Cook, Ferris M. Pfeiffer and James P. Stannard

Contact Info

Samuel E. Bish, bishs@missouri.edu or 573-882-5016; Nancy Parker, parkern@missouri.edu or 573-884-3553

Stem Cells Synergize With Immune Modulation for Treatment of Type I Diabetes

MU researchers have developed a novel method to treat type I diabetes (T1D). While insulin is necessary for survival, it does not treat the disease. The inventors have previously shown that an Ig-GAD2 regimen given to non-obese diabetic mice prevented disease progression. By accompanying their previous methods with the transfer of bone marrow cells from healthy donors, researchers were able to induce immune modulation of islet inflammation, repair islet vasculature and sustain regeneration and function of insulin-producing cells, leading to the reversal of overt T1D.

While the bone marrow cells gave rise to the endothelial cells in the pancreas, the new β-cells were of host origin. Also, the treatment ablated insulin-resistance associated with the onset of T1D. Thus, overcoming T1D requires both immune modulation and repair of the vascular niche to preserve the newly formed β-cells.

Potential Areas of Application
  • Type I diabetes treatment
Patent Status

Patent pending

Inventor(s)

Habib Zaghouani, Renu Jain and Randal Gregg

Contact Info

Charlie Hanford, hanfordc@missouri.edu or 573-882-0477

Sustained Delivery of Therapeutic Agents to the Retina

MU researchers have invented a novel technology to treat retinal degenerative disorders. This approach will allow continuous delivery of therapeutic agents, such as replacement enzymes, to the retina over long periods of time after a single treatment. They are performing preclinical studies treating the late-infantile form of Neuronal Ceroid Lipofuscinosis (NCL) using a canine model they have developed.

The canine model will allow assessment of safety and efficacy in using enzyme replacement, stem cell and gene therapies for this and related diseases. As a result, this new technology has the potential to provide an economic solution to treat retinal degenerative disorders with lower risk.

Potential Areas of Application
  • Diabetic retinopathy
  • Retinal degenerative disorders
  • Age-related macular degeneration
  • Neuronal Ceroid Lipofuscinosis (NCL)
Patent Status

Patent pending

Inventor(s)

Martin Katz, Joan R. Coates, Christopher Tracy, Rebecca E.H. Whiting and Jacqueline Pearce

Contact Info

Charlie Hanford, hanfordc@missouri.edu or 573-882-0477

Targeted Nano Platform for Delivery of siRNA and Drug

The present technology utilizes a gelatin nanoparticle to introduce both siRNA and a drug into a cell of interest. The drug is encapsulated in the nanoparticle while an antibody and the siRNA are conjugated to the surface of the nanoparticle.

The present work has demonstrated an effective means for treating un-druggable cancer mutations, in particular the KRas mutation. Once the nanoparticle is taken up into the KRas cell, the siRNA drives the cancer cell to use an alternate cellular mechanism. This alternate mechanism is then treated via the encapsulated drug, which causes cell death.

Potential Areas of Application
  • Oncology
  • Non-small cell lung cancer treatment
Patent Status

Patent pending

Inventor(s)

Srikar Raman and Raghu Kannan

Contact Info

Charlie Hanford, hanfordc@missouri.edu or 573-882-0477

Tool and Process Alignment and Site Preparation of Novel Rotator Cuff Grafts

Rotator cuff tears are one of the most common shoulder joint injuries. This injury occurs when one or more tendons that connect shoulder muscles to bone become torn, leading to pain and dysfunction of the arm. Between 1998 and 2004, more than 5 million physician visits were associated with rotator cuff problems. There are multiple options to help repair a rotator cuff injury depending on the severity. Smaller tears can be managed non-operatively; however, larger injuries require surgical reconstruction to restore arm function. In the U.S. alone, there are more than 50,000 surgeries completed every year. Tissue allografts are a common surgical technique used to repair tendon damage and fully restore function to the shoulder. However, without proper site preparation for the allograft site, failure rates of surgery can range from 20% to 70% leading to increased discomfort and additional surgeries later in life.

The current invention from MU researchers is an FDA-approved biomaterial used for rotator cuff repair/allograft site design as well as an improved surgery method that could increase surgery success rates.

Potential Areas of Application
  • Rotator cuff surgical repair
  • Rotator cuff reconstruction
Patent Status

Patent pending

Inventor(s)

Ferris Pfeiffer, James L. Cook and Matthew J. Smith

Contact Info

Samuel E. Bish, bishs@missouri.edu or 573-882-5016; Nancy Parker, parkern@missouri.edu or 573-884-3553

University of Missouri - St. Louis

Detecting and Treating Tb Using Lipase Inhibitors

Tuberculosis continues to kill nearly 1.5 million people annually, making it the most deadly infectious disease worldwide – especially in Sub-Saharan Africa, Russia and Eastern Europe. With the recent emergence of multiple drug-resistant strains, the increasing number of HIV cases, as well as the disappointing failures of the Gates-backed TB vaccine (MV85A), the need for novel therapeutic approaches is more pressing than ever. While there is growing awareness of the need for diagnosing tuberculosis and for drugs that can treat the disease, many of the promising new molecules in development are either repurposed drug compounds or new derivatives of known anti-mycobacterial drugs; none are reported to target intracellular lipid metabolism.

Researchers at UMSL, in collaboration with scientists at the National Center for Scientific Research in France, have developed powerful lipase inhibitors from enolphosphonate and enolphosphate families that show promising anti-tuberculosis activities on M. tb with no cytotoxicity effects. Additionally, fluorescently labeled compounds were shown to easily identify mycobacterial proteins that react with the inhibitors. Selective inhibition of lipolytic enzymes (both extracellular and intracellular) from M. tb by this new class of enolphosphonates may be used to develop more selective anti-microbial agents and, more specifically, anti-mycobacterial compounds.

Potential Areas of Application
  • Research tool
  • Diagnostics
  • Therapeutic
Patent Status

Patent pending

Inventor(s)

Christopher Spilling, Ben Martin, Stephane Canaan and Jean-Francois Cavalier

Contact Info

Craig Weilbaecher, weilbaecherc@umsl.edu or 314-516-4248

Novel Bis-Amino Acid-Based Compounds to Recover or Enhance Efficacy of Existing Antimicrobials

Antibiotic resistance has become a major health crisis. Bacteria have developed resistance to most of the known antibiotics, and the rate of discovery of new antibiotics has decreased dramatically in recent years. Patients who suffer from multidrug resistant (MDR) bacteria have few treatment options.

UMSL researchers have found that novel bis-amino acid-based compounds can be used as antimicrobials or used to recover or enhance efficacy of existing antimicrobials. These compounds have been tested against two Escherichia coli strains and an Staphylococcus aureus strain and were found to reverse antimicrobial resistance activity by up to 16-fold with minimum toxicity in mammalian cells.

Potential Areas of Application
  • Therapeutic against MDR bacteria or “superbugs”
  • Membrane-active antimicrobials
  • Adjuvant antibiotics
Patent Status

Patent pending

Inventor(s)

George Gokel, Joseph Meisel and Mohit Patel

Contact Info

Craig Weilbaecher, weilbaecherc@umsl.edu or 314-516-4248

University of Missouri - Kansas City

Biocompatible Bone Cement

Currently available commercial bone cements are composed of polymethyl methacrylates and have several notable disadvantages, including toxicity, lack of bioactivity, volumetric shrinkage, tissue necrosis and the generation of heat upon polymerization. Due to the high temperatures produced during polymerization, antibiotic treatment with bone cement is limited.

The current invention developed by UMKC researchers is a chemically initiated cement that is composed primarily of a monomer that has already proved effective in commercial dental composites. Our extensive testing of this new cement has found that this system is biocompatible, has a peak exotherm that is below 45 degrees C, has low shrinkage and contains excellent mechanical properties. This system provides a biocompatible alternative bone cement while maintaining good mechanical properties.

Potential Areas of Application
  • Orthopedics and dental
    • Use as a lower toxicity bone cement
    • Use in kyphoplasty or other procedures
    • Use in revision surgeries of implants with bone loss
Patent Status

Patent issued

Inventor(s)

Kathleen Kilway, Lynda Bonewald and Thomas Schuman

Contact Info

Eric Anderson, ericwa@umkc.edu or 816-235-5091

Dental Etching Gel With Collagen-Stabilizing Functionality

Current dental restorations may use a composite or an amalgam material. For various reasons, such as cosmetic preference, one may choose to utilize a composite material in a dental restoration. However, certain current composite tooth restorations exhibit a shortened lifespan compared to a tooth restoration performed with a traditional amalgam filling. This shortened lifespan may be due to a breakdown of at least a portion of the dentin collagen that interfaces with the composite material. Therefore, there is a need for compositions that can be used in a dental restoration process, such as a composite or ceramic dental restoration process that increase the stability of dentin collagen. One countermeasure to the issue is to incorporate a collagen cross-linker in the bonding procedure to stabilize dentin collagen against these degradations, and consequently, elongate the lifetime of restoration. Grape seed extract (GSE) is extremely valuable because it is non-toxic, and affords full protection of dentin collagen in a clinically acceptable 30 seconds. This use of GSE is thus far the only collagen cross-linker that exhibits un-compromised efficacy in acid.

Potential Areas of Application
  • Dental restorations
Patent Status

Patent pending

Inventor(s)

Yong Wang and Yi Liu

Contact Info

Eric Anderson, ericwa@umkc.edu or 816-235-5091

Light-Activated Insulin Depot

Worldwide there are tens of millions of insulin dependent diabetics. These patients must either subject themselves to multiple daily injections of insulin or have an insulin pump deliver the insulin to their abdomen by cannula. Insulin pumps can be inconvenient and carry the risk of infection, while daily injections are burdensome and prone to patient non-compliance and poor blood sugar control. Poorly controlled blood sugar is known to cause a wide range of serious short-term and long-term health problems in diabetic patients.

The current invention developed by UMKC researchers is a light activated insulin depot, in which a single injection under (or within) the skin contains potentially hundreds of injections worth of insulin. The insulin is then released as needed by subjecting the skin above the injection to a specific wavelength of light.

The depot material has three main elements: an insoluble polymer material, insulin and a light cleavable linker to join the polymer and insulin. The polymer keeps the insulin physically near the site of injection, while the light cleavable linker then joins insulin to this polymer. When transdermal irradiation occurs via pulses of LED light, the bond breaks, releasing a controlled amount of insulin that is proportional to the intensity and duration of the irradiation.

Potential Areas of Application
  • Weekly or monthly delivery of insulin via depot injection
  • Use in conjunction with a continuous glucose monitor to provide constant blood sugar levels
Patent Status

Patent pending

Inventor(s)

Simon Friedman, Piysh K. Jain, Dipu Karunakaran and Bhagyesh R. Sarode

Contact Info

Melanie Roberts, robertsmel@umkc.edu or 816-235-5090

Solubility Enabling Coating for Pharmaceuticals

UMKC researchers have developed a process to increase solubility of various pharmaceuticals in by applying a coating that utilizes sodium acetate during nanoencapsulation of pharmaceuticals for improved physiochemical and biological properties. Sodium acetate is an FDA-approved substance for human use. The nanoparticles exhibited higher encapsulation efficiency (~90%) of water soluble drugs such as tenofovir.

Potential Areas of Application
  • Improved delivery and solubility of poorly soluble drugs
  • Prevents the degradation of protein based drugs
  • Protects against moisture, oxidation, light and microbial growth
  • Increases the shelf-life of the pharmaceutical
  • Control of release rate of pharmaceutical
Patent Status

Patent pending

Inventor(s)

Bi Botti Youan and Albert Ngo

Contact Info

Eric Anderson, ericwa@umkc.edu or 816-235-5091