Imagine a bioactive dressing to help diabetic wounds heal faster, or a wearable device to catch septic shock before severe symptoms emerge, or a new therapeutic that prevents addiction in patients managing chronic pain with opioids.
These are three of a dozen new diagnostics, treatments, and products that teams of Arizona scientists and clinicians will work to develop over the next 18 months under the Flinn Foundation’s Seed Grants to Promote Translational Research Program.
The foundation is awarding $100,000 grants to 12 research groups in the eighth year of the seed-grants program, which focuses on projects addressing significant clinical needs. At the end of the grant period, two of the most successful grants will be awarded follow-on grants of up to $100,000 more.
The 2023 grantee cohort is the largest yet for the program, thanks to $200,000 in funding from the Tom and Catherine Culley Charitable Trust for two cancer-specific projects.
“We are honored to be joined in this grant program by the Culley Trust,” said Mary O’Reilly, Flinn Foundation vice president, bioscience research programs. “Their funds are enabling two projects of great promise: one to validate non-invasive diagnosis of gynecological cancers, another to make surgical treatment of neuroendocrine tumors more effective.”
Seed grants were awarded to four lead institutions: Arizona State University (3), Barrow Neurological Institute, Grand Canyon University, and University of Arizona (7). The selected projects, which include partnerships with Mayo Clinic, Banner University Medical Center, Banner MD Anderson Cancer Center and two private companies, were identified from a pool of more than 70 applications in an open process that drew proposals from 10 Arizona institutions.
While pursuing their projects, the grantee teams will work as a cohort, meeting quarterly to discuss progress, troubleshoot challenges, and learn from invited experts on product development and commercialization.
Since 2013, the Flinn Foundation has awarded 63 seed grants totaling about $7.5 million.
2023 Seed Grants
Arizona State University with Immunoshield Therapeutics: High-Throughput Biomanufacturing of Encapsulated Cell Products
Cell therapies are a new type of treatment with the potential to functionally cure a range of chronic diseases. However, allogeneic cell therapies require immune suppression, presenting serious acute risks to the patient, so that only a small fraction of patients currently qualify for cell therapy to treat their disease. The team’s method maximizes patient safety by containing cell therapies within an encapsulation device that can (1) reduce or eliminate the need for immune suppression and (2) enable the retrieval of cell therapies in the case of adverse events. This method has a distinct advantage in that it enables scalable, high-throughput biomanufacturing of encapsulated-cell products; this advancement will enable the production of sufficient doses to treat large numbers of patients. Principal Investigator: Jessica Weaver, Ph.D.
Arizona State University with Mayo Clinic: HistaHeal: Bioactive Dressing for Diabetic Wounds
The research team has developed a bioactive dressing, HistaHeal, to aid in healing complex wounds, including diabetic wounds. More than 6 million chronic and complex wound cases incur over $20 billion in health-care costs in the United States annually; diabetes delays repair and leads to chronic ulcers with high morbidity and mortality. Using biomaterial engineering and biomimetic cargo delivery, HistaHeal stimulates multiple reparative wound-healing signaling pathways to accelerate wound closure and improved functional recovery of skin. Combining a safe, naturally derived biopolymer with an endogenous pro-repair small molecule or specific receptor-targeting analogs, HistaHeal promotes rapid re-epithelialization of wounds to accelerate closure, while stimulating a pro-healing immune signature. Principal Investigator: Jordan R. Yaron, Ph.D.
Arizona State University with Mayo Clinic: A Point-of-Care Test for the Rapid Diagnosis of Valley Fever
In parts of central and southern Arizona, and in California’s Central Valley, up to 30% of patients with pneumonia have valley fever, a respiratory disease caused by inhalation of Coccidioides fungus spores. Unfortunately, it is difficult to distinguish valley fever from other pneumonia-causing viral and bacterial infections. Without a rapid, sensitive, specific test, an urgent-care physician is unlikely to order a valley fever test, because results may not be available until four days after the patient has been discharged. This team’s rapid test provides a clinically actionable answer in 10 minutes with a single drop of blood. Compared to the only other commercially available test for valley fever, this team’s rapid test is faster, quantifiable, more accurate, can use whole blood, and is amenable to consistent, high-quality production. Principal Investigator: Douglas Lake, Ph.D.
Barrow Neurological Institute: Neurostimulator Device for Assessment of Consciousness
Successful clinical management of critically ill patients with neurologic and traumatic pathologies or injuries centers on understanding the functional status of their central nervous system; level of consciousness is the most important clinical indicator of a patient’s neurologic status, and the Glasgow Coma Scale (GCS) is the standard examination of level of consciousness for clinical practice. Widespread use of the GCS has led to significant improvements in patient management, and the GCS has been incorporated into many widely used clinical decision-making algorithms, but it has several problems that limit its potential and have caused some experts to question its use. This team is developing a new device and methodology for the GCS that will not rely on mechanical pain stimulation. Principal Investigator: Brandon Fox, M.D.
Grand Canyon University: Sepsis Dx: A Septic Shock Screening Device
Sepsis—wherein serious organ/tissue failure is caused by a systemic inflammatory response from either a viral or bacterial infection—is typically detected via fever, breathing, heart rate, and lethargy. To decrease mortality rate and reduce drug resistance, sepsis needs to be diagnosed as early as possible following infection. To accomplish this, a simultaneous sepsis biosensor sensing system will be developed to monitor three biomarkers indicating the presence of sepsis, enabling clinicians to quickly diagnose all cases of sepsis regardless of origin and thus decrease the mortality rate. The goal of this project is development of a multi-biosensor, wearable device to diagnose sepsis more rapidly. Principal Investigator: Jeff LaBelle, Ph.D.
University of Arizona: Development of a Novel Therapy to Treat COPD
Chronic obstructive pulmonary disease (COPD), the third leading cause of death worldwide, is a group of lung diseases, including emphysema and chronic bronchitis, characterized by recurrent infections and inflammation. Recent studies have reported decreased levels of club cell secretory protein (CC16) in COPD patients, and this team has found that CC16 delivered into the bloodstream rescues lung function, limits immune-cell migration into the lungs, and enhances epithelial host responses to pathogens; it protects from COPD as an anti-inflammatory protein in circulation and by promoting secretion of defensive factors in the respiratory epithelia to aid in pathogen clearance. The team is developing CC16-derived peptidomimetics and is working to enhance solubility, efficacy, and stability, while minimizing size and toxicity. Principal Investigator: Julie Ledford, Ph.D.
University of Arizona: Targeting TDP–43 for Neurodegenerative Diseases
TDP–43 (transactive response DNA binding protein of 43 kDa) is the common hallmark disease protein for various major neurodegenerative diseases. Mitochondria are closely linked to neurodegeneration, and have recently emerged as a critical target of TDP–43. The project team has reported a novel peptide-based TDP–43 inhibitor named “PM1” that was specifically designed to disrupt the association of TDP–43 with mitochondria and has been shown to prevent and even reverse disease progression in different neurodegeneration models. The promising prior work warrants further development and optimization of this novel TDP–43 inhibitor. The work proposed in this project will enable the project team to commercialize TDP–43 inhibitors as a common disease-modifying care for neurodegenerative diseases. Principal Investigator: Xinglong Wang, Ph.D.
University of Arizona with Banner University Medical Center: Gynecologic Cancer and Disease Diagnostic with At-Home Test Collection
Diagnostic options for uterine diseases are limited to biopsy or suboptimal imaging. Biopsy can cause anxiety, physical discomfort, and pain, and some uterine conditions, such as adenomyosis, can only be diagnosed after surgical removal of the uterus; this invasive diagnostic approach creates a barrier for early detection and treatment. This project team has previously demonstrated that minimally invasive cervicovaginal lavage (CVL) sampling allows detection of biomarkers for a range of gynecologic conditions and that these biomarkers can predict disease severity. The team’s ultimate goal is to create an at-home test for gynecologic diseases, which will benefit women by improving detection and consequently decreasing health inequities throughout Arizona and including underserved and rural populations. Principal Investigator: Melissa Herbst-Kralovetz, Ph.D.
University of Arizona with Banner University Medical Center: A Targeted Therapy for Intracranial Hemorrhage
Bleeding in the brain, or intracranial hemorrhage (ICH), is a devastating medical condition, and no medical therapy improves outcomes. Primary ICH affects 5.3 million people worldwide each year, 60% of patients die, and most survivors are left disabled. Data suggests that matrix metalloproteinase–9 (MMP–9) worsens ICH and contributes to brain damage. The project team is already developing an MMP–9 inhibitor that markedly decreases brain bleeding in patients with another condition, ischemic stroke. For this project, the team will test whether this MMP–9i can also reduce bleeding in ICH. Data that MMP–9 inhibition is effective for ICH would provide the rationale to support development of this MMP–9i to treat this devastating disease. Principal Investigator: Guy Reed, M.D.
University of Arizona with Banner University Medical Center: Transcranial Acoustoelectric Imaging of Deep Brain Stimulation Currents
Deep brain stimulation (DBS) is used to alleviate symptoms of Essential Tremor and Parkinson’s Disease, with increasing demand for treating conditions like depression and Alzheimer’s disease. The effectiveness and failure rate of DBS strongly depends on location of the leads and specific parameters for stimulation; however, there remains an unmet clinical need for an in vivo method to safely and noninvasively pinpoint electrode contacts to guide placement of the DBS device during insertion, image current flow during behavioral assessment and setting stimulation patterns, and long-term monitoring of device integrity after implant. This project would devise a real-time transcranial acoustoelectric brain imaging (tABI) system capable of remotely mapping DBS currents at the millimeter scale. Principal Investigator: Russell Witte, Ph.D.
University of Arizona with Banner University Medical Center and M.D. Anderson Cancer Center: Neuroendocrine Tumor Surgical Localization
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are the second most common digestive cancer and would greatly benefit from next-generation intraoperative imaging systems to enable accurate localization and margin definition. The key to improving GEP-NET resection is to develop a laparoscopic imager for minimally invasive surgery that enables wide-area tumor localization and high-resolution inspection for margin definition. This team has worked toward implementing a contrast agent for GEP-NETs for wide-field fluorescence imaging and has shown that multiphoton microscopy can differentiate clear margins between tumor and normal tissue. The team has designed the architecture for a laparoscope implementing this technology for GEP-NET resection and the next step is to build and test the device. Principal Investigator: Travis Sawyer, Ph.D.
University of Arizona with Innoventyx LLC: Novel Approach to Eliminate Opioid Addiction in Pain Management
Opioid analgesics (OA), are the most efficacious drugs for the management of chronic pain. In 2020, about 143 million opioid prescriptions were dispensed in the United States; unfortunately, 21–29% of patients with chronic pain misuse prescribed OA, and 8–12% develop opioid addiction (so-called Opioid Use Disorder or OUD). To prevent drug addiction in pain management, the project team proposes to use novel first-in-class drug candidates that, in combination with OA, can control/prevent addiction while analgesic properties remain unchanged. The team has developed a library of compounds that target key biological activities involved in pain and OUD. The project team’s front-runner drug candidate prevents development of addiction when used in combination with morphine, while showing improved analgesic effects. Principal Investigator: John Streicher, Ph.D.