Jianjie Ma, PhD
A scientific discovery aimed at stopping dangerous immune-system overreactions could soon offer hope to patients facing some of the most dangerous medical emergencies—sepsis, acute respiratory distress syndrome (ARDS), and other forms of severe inflammation.
Sepsis and ARDS remain among the leading causes of death in intensive care units, yet no U.S. Food and Drug Administration (FDA)-approved therapy directly targets the underlying immune dysfunction that drives organ failure. By identifying a key molecular driver, a UVA research team led by Jianjie Ma, PhD, uncovered a precise target in a disease area long defined by nonspecific and ineffective treatments. This new target represents a new therapeutic strategy that focuses on interrupting a core biological mechanism rather than treating symptoms. If successful, this approach could shift the treatment paradigm for sepsis, ARDS and other inflammatory diseases that have few effective options
Stopping the Body From Hurting Itself
When the immune system overreacts during severe infections or trauma, it can cause catastrophic inflammation that damages blood vessels, floods the lungs, and harms organs. UVA scientists believe that a molecule called CitH3 plays a central role in this runaway process. Instead of helping the body fight infection, CitH3 can push the immune system into a dangerous cycle that worsens illness.
“We found that CitH3 is one of the key triggers that turns helpful immune responses into harmful ones,” said Dr. Ma, a UVA scientist, director of the Division of Surgical Sciences at the UVA School of Medicine, and founder of HTIC, Inc. “If we can block it, we can protect tissues and organs at the very moment they are most vulnerable.”
The new therapy, called hCitH3-mAb, is a carefully designed antibody that binds to CitH3 and neutralizes it. Developed through years of research and successful preclinical studies, it will first be tested in healthy volunteers and then in patients with sepsis-induced ARDS—a life-threatening condition with few effective treatments.
The Phase 1a study will be led by Alpha Fowler, MD, a sepsis and ARDS specialist at Virginia Commonwealth University (VCU). Imre Noth, MD, of UVA Health, a national leader in lung disease research, will co-lead the multicenter Phase 2a trial.
“With more than 35 years of caring for ICU patients with sepsis, I look forward to working with this outstanding group to execute the clinical trial,” said Dr. Fowler. “My hope is that we can finally ‘crack the code’ of sepsis and bring this first-in-class immunotherapeutic to patients who desperately need new options. This could save many lives.”
The milestone also reflects the growing impact of the Paul and Diane Manning Institute of Biotechnology at UVA. The institute’s mission is to accelerate the translation of discoveries into real-world therapies. This aligns directly with the development of this potential new therapy. “This is exactly what the Manning Institute was built to do, transform pioneering science into medicines with the potential to save lives,” said Dr. Mark Esser, Chief Scientific Officer and Head of the Paul and Diane Manning Institute of Biotechnology at UVA. “The hCitH3-mAb program showcases the innovation emerging from UVA investigators and the collaborative spirit required to move a complex biologic from the lab to first-in-human studies. It’s an exciting moment for UVA, HTIC, and most importantly, for sepsis patients who desperately need new therapies.
A Team Effort to Save Lives
Moving a new therapy from the lab to the clinic requires scientific collaboration, advanced manufacturing, and significant funding. The UVA spin-off company partnered with SparX Biopharmaceutical Corp. to produce the treatment and prepare it to meet FDA standards. Funding from the Virginia Catalyst Program helped propel the work forward.
“This is the kind of impact universities can have when discovery science, clinical expertise, and regional biotech innovation work together,” said Dr. Ma. “Our goal is simple: get a lifesaving therapy to patients who desperately need it.”
Media contact:
Catherine West: Hyk5sz@virginia.edu
Reprinted from the Office of the Vice President of Research
Filed Under: Research