LITTLE ROCK —The first rapid diagnostic test for acetaminophen toxicity has cleared a major hurdle on its long road to the marketplace from the University of Arkansas for Medical Sciences (UAMS).

The test’s inventors, UAMS’ Laura James, M.D., Jack Hinson, Ph.D., and Dean Roberts, Ph.D., received a three-year, $3.2 million National Institutes of Health (NIH) Small Business Technology Transfer (STTR) grant to conduct the final phase of study before seeking Food and Drug Administration (FDA) approval of the blood test.

The grant will include the final development of the new laboratory test AcetaSTAT, a rapid assay to diagnose acetaminophen liver injury, and a clinical trial involving multiple centers to evaluate the test’s performance.

The new blood test can detect blood markers for liver injury from acetaminophen overdose in about 20 minutes. Acetaminophen is the most common drug for pain and fever, and it is the most common cause of liver failure in the United States.

“It has been a long journey, but it has been fun and exciting because we’re moving toward a big contribution in health care,” said James, who founded her company, Acetaminophen Toxicity Diagnostics (ATD) LLC, in 2006 with Roberts and Hinson. James also serves as the director of the UAMS Translational Research Institute.

ATD developed the test in conjunction with UAMS and Arkansas Children’s.

Physicians have no FDA-approved test to confirm the diagnosis of acetaminophen liver injury. They must rely on patient history and nonspecific tests of liver injury when evaluating patients with liver injury due to acetaminophen overdose.

William M. Lee, M.D., a liver disease specialist at the University of Texas Southwestern Medical Center at Dallas, is a co-investigator on the clinical trial and has been involved in prior testing of the assay. James also credits him for giving her the idea to pursue a rapid, point-of-care test.

“I have been impressed that the assay provides a reliable yes/no answer as to whether acetaminophen is responsible for the liver injury,” Lee said. “I look forward to seeing AcetaSTAT being available in any Emergency Department worldwide. Having the test will ensure that more patients receive the right diagnosis and appropriate treatment.”

James is optimistic about the assay’s prospects for FDA approval, given its past performance. She has assembled a strong, interdisciplinary team to conduct the multisite clinical trial. The team members include (in alphabetical order):

• David Baker, CEO of ATD
• Hans Boehringer, Ph.D., vice president, Technology Development, DCN Diagnostics; consultant
• Ruofei Du, Ph.D., UAMS Department of Biostatistics; co-investigator
• Maryam Garza, Ph.D., College of Medicine Department of Biomedical Informatics; co-investigator
• Hinson, chief scientific officer; co-investigator
• Brendan O’Farrell, Ph.D., president, DCN Diagnostics; consultant
• Jeannette Lee, Ph.D., professor, UAMS Department of Biostatistics; co-investigator
• Fred Prior, Ph.D., distinguished professor and chair, College of Medicine Department of Biomedical Informatics; co-investigator
• Roberts, director of Research and Development; co-investigator

Jessica Snowden, M.D., associate professor and chief, Division of Pediatric Infectious Disease, College of Medicine Department of Pediatrics; and co-leader of the NIH-funded IDeA (Institutional Development Awards Program) States Pediatric Clinical Trials Network Data Coordinating and Operations Center; co-investigator

Principal Investigator: Jeffrey Stambough, M.D., Assistant Professor, Hip and Knee Reconstruction, Department of Orthopaedic Surgery, College of Medicine

Summary: A randomized trial evaluating a preoperative, medically supervised weight loss program. The program includes meal plans, nutritional supplements, and daily engagement via a smartphone app. 

Significance: Patients with body mass indexes above 40 are prohibited from having certain elective surgeries, such as hip and knee replacements. The study will help determine if the intervention is effective in helping patients achieve weight-loss goals that are known to improve surgery outcomes.
 

TRI Services: Budget development, Medicare coverage analysis, regulatory services.

Sponsor: 20Lighter, LLC

TRI’s KL2 Mentored Research Career Development Scholars Program announced nine new scholars for 2022-2023, its largest-ever class.

These promising early-career researchers receive two years of funded support and mentored translational research training. The program selects scholars through a competitive application process and provides 75% salary support and up to $25,000 a year for research, tuition, travel and education.

Additional scholars were selected this year thanks to funding support from the College of Medicine, Winthrop P. Rockefeller Cancer Institute, Arkansas Children’s Research Institute and Central Arkansas Veterans Healthcare System. 

The scholars, their project titles and primary mentors are:

Jennifer Andersen, Ph.D.

Jennifer Andersen, Ph.D., assistant professor, Northwest Regional Campus, Office of Community Health and Research

“Feasibility and Acceptability of a Remote Glucose Monitoring Program for Pregnant Marshallese Women whose Pregnancies are Complicated by Diabetes”

Primary Mentor: Hari Eswaran, Ph.D.

Timothy “Cody” Ashby, Ph.D., M.S.

Timothy “Cody” Ashby, Ph.D., M.S., assistant professor, College of Medicine Department of Biomedical Informatics

“Determining Multiple Myeloma Risk and Heterogeneity at a Single-Cell Resolution”

Primary Mentor: Fenghuang Zhan, M.D., Ph.D.

Nishank Jain, M.D.

Nishank Jain, M.D., assistant professor, College of Medicine Department of Internal Medicine, Division of Nephrolog

“Platelet, Inflammation and Thrombosis in Chronic Kidney Disease”

Primary Mentor: John Arthur, M.D., Ph.D.

Akilah Jefferson-Shah, M.D., M.Sc.

Akilah Jefferson-Shah, M.D., M.Sc., assistant professor, College of Medicine Department of Pediatrics, Division of Allergy and Immunology. 

“Delineating Individual and Population-level Factors that Contribute to Disparate Pediatric Asthma Outcomes and to Develop Predictive Models for Identifying Children at Risk for Poor Outcomes”

Primary Mentor: Tamara Perry, M.D.

Nakita Lovelady, Ph.D., MPH

Nakita Lovelady, Ph.D., MPH, assistant professor, Fay W. Boozman College of Public Health, Department of Health Behavior and Health Education.

“A Feasibility Study for the Implementation of a Hospital-based Violence Intervention Program in the Rural South”

Primary Mentor: Nickolas Zaller, Ph.D.

Sayem Miah, Ph.D.

Sayem Miah, Ph.D., assistant professor, College of Medicine Department of Biochemistry and Molecular Biology

“Targeting BRK with PROTAC to Halt Metastatic Triple Negative Breast Cancer”

Primary Mentor: Alan Tackett, Ph.D.

Deepa Raghavan, M.D.

Deepa Raghavan, M.D., assistant professor, College of Medicine Department of Internal Medicine, Division of Pulmonary and Critical Care; medical director, VA Medical ICU

“Implementation of COPD Clinical Practice Guidelines with Incorporation of Telehealth”

Primary Mentor: JoAnn Kirchner, M.D.

Jennifer Rumpel, M.D.

Jennifer Rumpel, M.D., assistant professor, College of Medicine Department of Pediatrics, Neonatology Section

“Advancing Care of Neonates with Acute Kidney Injury Utilizing the Children’s Hospitals Neonatal Consortium Database”

Primary Mentor: Laura James, M.D.

Amy Sato, Ph.D.

Amy Sato, Ph.D., assistant professor, College of Medicine Department of Physiology and Cell Biology

“Identification of Cardioprotective Signatures Induced by Targeting MuRF1 and Vitamin D Signaling in Glucocorticoid-Associated Cardiac Disease”

Primary Mentor: Marjan Boerma, Ph.D.

A new video sponsored by the Translational Research Institute is being used to help raise awareness among researchers about the inclusion of older adults in research. The five-minute video also has tips for helping researchers recruit more adults over age 65.

The video was produced in collaboration with the UAMS Northwest Regional Campus, the Center for Health Literacy and Office of Communications and Marketing. It features Jennifer Vincenzo, Ph.D., MPH, PT, an associate professor in the UAMS College of Health Professions and a TRI KL2 Research Career Development scholar.  

Vincenzo said adults over 65 are often overlooked or excluded from research, jeopardizing efforts to ensure that new drugs and other prescription health interventions are safe and effective for this population.   

Older adults are excluded in 20% of clinical trials, and nearly half of trials have eligibility criteria that disproportionately impact older adults, based on an analysis of 109 clinical trials.

For example, although heart disease is a leading cause of death in the U.S., over 50% of clinical trials of potential treatments for ischemic heart disease excluded patients over ages 75 or 80.

Similarly, because of age limits and medical exclusions, older adults have been prohibited from participation in more than 50% of COVID-19 clinical trials and up to 100% of vaccine trials.

Watch the video here.

A virus test developed at the University of Arkansas for Medical Sciences (UAMS) to help prevent a common cat cancer won the top $25,000 prize at the Arkansas Governor’s Cup Collegiate Business Plan Competition on March 31.

Shana Owens, Ph.D., a postdoctoral fellow in the UAMS College of Medicine Department of Microbiology and Immunology, invented the test as her project in the UAMS Translational Research Institute’s Health Sciences Innovation and Entrepreneurship (HSIE) Training Program. The Governor’s Cup victory was followed by two more in the national Heartland Challenge April 16, bringing the total prize amount to $29,500.

The program, conducted in partnership with the University of Arkansas Sam M. Walton College of Business, provides two years of training to postdoctoral fellows selected through a competitive application process.

After inventing the test, a lateral flow assay that Owens named GammaFlow, she formed a company, GammaVet. Her Governor’s Cup win March 31 was following by a $3,000 Investor Roundtable competition and the $1,500 special award Woman-Run by Wright Lindsey Jennings at the Heartland Challenge.

She and her team will use the prize money to support commercial development of GammaFlow.

Owens was aware that, like humans, cats are susceptible to viruses that cause cancers. Interviews with local veterinarians revealed that gastrointestinal lymphoma, which stems from a virus, is the most common cat cancer they treat. Importantly for Owens’ entrepreneurial goal, there is currently no diagnostic test for Felis catus gammaherpesvirus 1, which causes the deadly cancer of the digestive tract.

In March 2021, Owens first proposed her virus test to program leaders at an HSIE class. By September, she was pitching it to the UAMS Patent Committee, and by November, she had a provisional patent filed on her technology.

“This really snowballed. If you had asked me a year ago if I would be working on an assay for cat right now, I probably would have told you you’re crazy,” Owens said. “Now we’re looking at dimensions for shipping in boxes and thinking about where we would manufacture and store our products.”

Once completed, the rapid test will allow a veterinarian to use a small blood sample to determine within minutes if a cat has the virus that would predispose it to GI lymphoma.

“GI lymphomas are such a big problem that local vets want answers, so they’ve been helping our team develop the prototype,” Owens said.

The GammaFlow prototype received additional help from $2,000 that her team won at a 2021 pitch competition by the Office of Entrepreneurship at the University of Arkansas.

Owens is CEO of GammaVet, whose other founding members are:

• Zach Waldrip, Ph.D., chief scientific officer; HSIE scholar and postdoctoral fellow in the College of Medicine Department of Surgery, Division of Surgery Research.
• Brett LittleJohn, chief finance officer; also director of product development and sourcing at Sam’s Club and an executive MBA candidate.
• Braden Bateman, chief marketing officer; a former John Deere sales representative and a master’s candidate in agricultural economics.

“The HSIE Program has really changed how I view my science,” Owens said. “Learning how to see basic bench science from an entrepreneurial perspective has been an amazing experience.”

Other HSIE trainees have also been part of teams that won recent competitions. They are:

• John Sherrill, Ph.D., MPH, with Horizon Health Solutions, which won $5,000 for third place at the Stu Clark New Venture Championships in Manitoba, Canada; and $3,000 for first place in the elevator pitch competition at the Heartland Challenge. The company is commercializing a software-as-a-service called PriceView, the first of its innovative solutions for pharmacies. Sherrill is a postdoctoral fellow in the College of Medicine Department of Orthopaedic Surgery.
• Emily Darrigues, Ph.D., with CiphrX Biotechnologies, which won $5,000 for fourth place in the Heartland Challenge. The brain cancer diagnostics company has a patent-pending test kit for same-day genetic sequencing within the hospital. Darrigues is a postdoctoral fellow in the College of Medicine Department of Neurosurgery.

The HSIE Program is supported by the UAMS Translational Research Institute, which is funded by a National Institutes of Health Clinical and Translational Science Award through the National Center for Advancing Translational Sciences.

A UAMS team’s article on COVID-19 vaccine hesitancy recently received the 2022 Clinical and Translational Science Award from the American Society for Clinical Pharmacology & Therapeutics (ASCPT).

The study, “COVID-19 Vaccine Hesitancy: Race/Ethnicity, Trust and Fear,” became the most downloaded paper in 2021 from ASCPT’s journal Clinical and Translational Science. The study used TRI’s ARresearch registry of potential research volunteers and was conducted by researchers at the Office of Community Health and Research, directed by Pearl A. McElfish, Ph.D., MBA. Don Willis, Ph.D., an assistant professor, is the paper’s lead author.

John Wagner, M.D., Ph.D., the Clinical and Translational Science journal’s editor-in-chief, said the award recognizes the paper that most reflects ASCPT’s goals of advancing diversity, equity and inclusion (DEI).

“This paper best fit the bill as a terrific example both of DEI and translational science,” Wagner said.

The award was announced by ASCPT during its annual meeting in March.

The paper resulted from a survey of Arkansans who have joined the UAMS Translational Research Institute’s ARresearch registry, which by March included more than 8,400 residents from all 75 counties.

“We used the ARresearch database exclusively, and the sample was really good and really diverse in terms of race and ethnicity,” Willis said.

The ARresearch registry generated a 31.6% survey response rate (1,288 of 4,077 registrants contacted), a high percentage considering the extensive length of the survey, Willis said. The high number and diversity of respondents helped generate the paper’s high quality results.

The Study Highlights section of the paper states, “This study was the first to look at sociodemographic differences in COVID-19 vaccine hesitancy in a highly vulnerable rural state that ranks third for prevalence of individuals at high risk for serious illness from COVID-19. The COVID-19 vaccine hesitancy was highest among respondents with lower household income, some college and little to no fear of infection from COVID-19.”

Willis said access to the free registry made it possible to conduct the study much more quickly. It also avoided the high cost of purchasing valid emails or phone numbers for a random sample survey.

“The registry is an incredible resource because it includes people who are already motivated to participate in research,” he said. “It’s very different from random sample surveys in which you’re emailing or calling people who may not want to be bothered, and the response rate with those can be very low.”

By March, the comprehensive survey had led to five published papers and more were in production.

TRI’s Inaugural Research Day 2022 on Tuesday drew 125 attendees and included a poster session with 33 poster presenters.

Held at Heifer International Headquarters in Little Rock, the full-day program included two keynote speakers and six presentations from researchers whose work has been supported by TRI.

The posters represented TRI-funded programs including pilot awards, Health Science Innovation and Entrepreneurship Training Awards, NCATS Supplemental Awards, KL2 Mentored Research Career Development Awards, Implementation Science Scholar Awards, Data Science Scholar Awards, Team Science Voucher Awards, and the Clinical Informatics Fellowship Program in the Department of Biomedical Informatics.

The poster winners are:

Overall Visual:
Cody Ashby, Ph.D., M.S., Assistant Professor, College of Medicine Department of Biomedical Informatics (Pilot)
Racial Differences in Multiple Myeloma Genomics and Outcome in Rural Populations

Overall Content:
Yasir Rahmatallah, Ph.D., Assistant Professor, College of Medicine Department of Biomedical Informatics (Data Science)
Disease Trajectory Analysis From Electronic Health Record

Overall Oral/Discussion:
Melissa Zielinski, Ph.D., Assistant Professor, College of Medicine Department of Psychiatry (Pilot)
Incarcerated Pregnant Women in Arkansas: Expanding Foundational Knowledge and Building Research Capacity

Overall Impact:
Isabelle Racine Miousse, Ph.D., Assistant Professor, College of Medicine Department of Biochemistry and Molecular Biology (KL2)
Dietary Methionine Restriction Improves the Response to Immune Checkpoint Inhibitors

People’s Choice:
Nishank Jain, M.D., Assistant Professor, College of Medicine Department of Internal Medicine (Data Science) (with assistance from Layth Al-Hindi, medical student)
Event Rates and Risk Factors for Intracranial Bleeds Among Dialysis Patients on P2Y12 Inhibitors

The posters were judged by a who’s who of UAMS research leaders, including College of Medicine Dean Susan Smyth, M.D., Ph.D. Other judges were: Paul Drew, Ph.D., Laura Dunn, M.D., (new chair of the Department of Psychiatry) Bradley Martin, Pharm.D., Ph.D., Richard Owen, M.D., and Jessica Snowden, M.D.

View all of the poster entries in the Research Day Program.

Principal Investigator: Vivian Shi, M.D., Associate Professor, Department of Dermatology, College of Medicine.

Summary: A five-year longitudinal observational study tracking outcomes of patients with chronic inflammatory skin conditions, including atopic dermatitis (eczema), alopecia, hidradenitis suppurativa, vitiligo and psoriasis.

Significance: Characterization of disease activity over time, including response to treatments and analysis of biospecimens, will inform clinical practice by identifying the occurrence and impact of comorbid medical conditions and aid the design of more targeted therapies.

TRI Services: Budget development, Medicare coverage analysis, regulatory and research nurse coordinator services.

Sponsor: TARGET PharmaSolutions

In this issue of The TRIbune newsletter, we highlight the work of two researchers who used TRI’s Team Science Voucher Program to help obtain large federal grants. Craig Porter, Ph.D., received a five-year, $2 million award from the National Institute of General Medical Sciences.

Corey Hayes, Pharm.D., Ph.D., MPH, leverage his team science voucher to earn a $1 million Veterans Affairs Career Development Award.

This issue also features Vivian Shi, M.D., in our TRI Study of the Month and the mentorship awards to implementation scientists Geoffrey Curran, Ph.D., Taren Swindle, Ph.D., and Melissa Zielinski, Ph.D. They took three of the six UAMS mentorship awards announced at Mentors Appreciation Day in January.  Read The TRIbune.

Principal Investigator: Subodh Devabhaktuni, M.D., Assistant Professor, Division of Cardiology, Department of Internal Medicine, College of Medicine.

Summary: A phase 3 multi-center efficacy and safety study of Etripamil Nasal Spray to treat spontaneous episodes of Paroxysmal Supraventricular Tachycardia (PSVT), an arrhythmia.

Significance: While not lethal, PSVT episodes can cause panic that sends patients to the emergency department. If approved by the FDA, Etripamil Nasal Spray could be used in the home to stabilize patients’ heart rhythms.    

TRI Services: Budget development and negotiation, Medicare coverage analysis, and regulatory management

Sponsor: Milestone Pharmaceuticals Inc.