2020 MBArC Funded Projects

Non-resistant Combination Antibiotic for Hospital Acquired Pneumonia and Ventilator Associated Pneumonia (HAP/VAP) (UMSL)

Antimicrobial resistance is a major healthcare concern as identified by the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO). Hospital acquired infections have a high financial burden on the healthcare system and contribute significantly to inpatient morbidity and mortality in the United States. One such hospital acquired infection is Hospital Acquired Pneumonia and Ventilator Associated Pneumonia (HAP/VAP) that affects over 350,000 patients annually with a primary target market of approximately $200 Million in the US. HAP/VAP that are caused by multidrug resistant (MDR) Gram-Negative bacteria (GNB), are difficult to treat and lack effective first line therapies. To address this unmet need, the team is developing a non-resistant, broad-spectrum combination antibiotic that can be administered once-a-day intravenously to hospitalized patients suffering from HAP/VAP. The innovation is in the new adjuvant that allows for passage of an antibiotic into the bacteria and inhibition of the bacterial resistance mechanism. The adjuvant also holds promise as a platform as it can be combined with multiple different antibiotics for the treatment of other multidrug resistant infections. This novel therapy has the potential to be fast-acting and effective, thereby benefiting patients and saving lives.

Fistula Fix: Fistula Closure Device (KUMC/KU)

A fistula is a communication between two hollow or tubular organs. While various types of fistulas can develop inside the human body, the most common and problematic is the enterocutaneous fistula (ECF), an abnormal communication between the small or large bowel and the skin. More than 71,000 hospitalizations for enteric fistulas occur yearly in the US. Common causes of ECF formation include surgery, inflammatory bowel disease (e.g. Crohn’s disease), trauma, malignancy and foreign body. The associated mortality rate is substantial (6-33%). Estimates also suggest that the development of an ECF can increase ICU length of stay (LOS) nearly 4-fold and the hospital LOS 5-fold. Hospital costs can increase accordingly. While therapeutic options are limited, medical devices such as clips, plugs and fibrin-based sealants have very low success rates. Conservative therapy that includes withholding of food along with intravenous delivery of fluids, nutrition and antibiotics for many weeks to months is prescribed initially to nearly all patients. However, it fails in 70-80% of cases. Surgical intervention is typically the treatment of choice when the fistula fails to close, however, 14-34% of those who undergo a fistula takedown surgery develop a new fistula. To address this widespread clinical problem, the team plans to develop a non-surgical intervention that can effectively close fistulas. Cyanoacrylate (‘superglue’)-based adhesives like Trufill® are approved for use of wound closure. However, the inability to control these adhesives after their injection through a delivery device (i.e. catheter) has substantially limited their use internally. The proposed device, Fistula Fix, offers precise delivery and control of these powerful tissue adhesives to achieve closure of many fistula types that currently have no effective treatment options. Fistula Fix is designed to be a non-surgical, catheter-based procedure that has the potential to offer accurate control and placement of adhesive accomplished by mixing a proprietary magnetic nanoparticle with the cyanoacrylate tissue adhesive, and controlling the position of the adhesive/nanoparticle solution with an electromagnetic field near the end of the delivery catheter until the adhesive polymerizes.

Late Acting Therapeutic Against Acetaminophen Induced Liver Injury (KUMC)

Acetaminophen (APAP), one of the most commonly used analgesics worldwide, is present in many prescription drugs and over-the-counter medicines. Though safe at therapeutic doses, APAP overdose induces liver cell death, ultimately compromising liver function, and resulting in acute liver failure. It is the most common cause of acute liver failure in the United States and leads to around 56,000 emergency room visits, 30,000 hospital admissions and 500 deaths annually. The only FDA approved treatment for an APAP overdose is N-acetyl-cysteine (NAC), which is most effective when administered early after APAP consumption. However, patients typically present much later to the clinic once symptoms are evident, by which time liver injury is already progressed and effectiveness of NAC is diminished. Thus, there is a critical need for a late-acting therapeutic option which, when administered in the clinic, could prevent development of acute liver failure even in patients with ongoing liver injury. The proposed product, MSCTC-0010, being developed by the Midwest Stem Cell Therapy Center, is one such intervention. In targeting liver regeneration, it is uniquely different from the standard of care, NAC, and has promising therapeutic potential.

Targeted Nanoparticle Therapeutic for Hematological Cancers (MU)

Hematological cancers are malignancies of blood-forming tissues for which over 170,000 new diagnoses are expected this year according to the Leukemia & Lymphoma Society. The most common hematological cancer is lymphoma which is characterized by the development of tumor masses in the lymph nodes. The most frequently diagnosed type of lymphoma is the non-Hodgkin’s subtype, designated diffuse large B cell lymphoma (DLBCL). Though frontline treatment consisting of infusion chemotherapy sometimes supplemented with radiation or intrathecal chemotherapy is quite effective in treating DLBCL, relapse or refractory disease occurs in 30-50% of all patients, and is associated with a very poor prognosis. There is a significant need for a new treatment, and while a variety of promising therapeutics are currently being developed to improve frontline and/or intensification treatment approaches, they possess considerable drawbacks. To address this unmet need, the team of translational researchers has created a targeted nanoparticle-based composite drug delivery system that is envisioned to be a safer and more efficacious alternative treatment modality for difficult to treat, relapsed or refractory DLBCL. The novel therapeutic will also have the potential to be expanded into an adjunct to or replacement for standard of care R-CHOP (Rituximab, cyclophosphamide, doxorubicin, vincristine, and predisone) therapy in the future. Additionally, DLBCL is one of the most common and deadliest malignancies in canines, presenting a comprehensive pathway to translation in both companion animals and humans.