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Researchers Receive $2.5 million NIH Grant to Study Potential Sepsis Drug Therapies

Tuesday, July 5, 2022

Every year, nearly 11 million people around the world die of sepsis, and there is currently no FDA approved drug to treat the condition. URMC researchers are out to change that.

When Anthony Pietropaoli, M.D., first met Minsoo Kim, Ph.D., over 15 years ago, they found they had common scientific and clinical interests, and started a fledgling translational research project combining a small cohort of septic patients with preclinical investigations using a mouse model of sepsis. In 2014, they earned a $4 million grant from the National Institutes of Health to study how immune cells would penetrate blood vessels. Fueled more recently by a URSMD Scientific Advisory Committee Faculty Pilot Incubator award, they have continued to build on that work and grow their collaborative sepsis research program.

This new grant from the NIH is for $2.5 million over four years, and will allow Pietropaoli, a professor of Medicine in Pulmonary & Critical Care Medicine, and Kim, the Dean’s Professor of Microbiology and Immunology, to conduct research for their ambitious proposal: determining whether a specific blood complement factor could be used as a drug treatment for sepsis.

With funding from previous grants and their intense study of blood markers, they discovered that the complement protein C1q, which occurs naturally in our blood and is one of the bacteria fighting molecules, has other functions, such as promoting resolution of inflammation. They aim to do a deep dive into C1q to see if harnessing its functions can lead to a new therapeutic treatment. 

Drug therapies for sepsis have been difficult to obtain so far because the patient population is so diverse. There is no one treatment for the wide variety of situations of septic patients.

“The goal of this new research,” said Pietropaoli, “is to determine whether the production of C1q by neutrophils in septic patients is an important prognostic marker in our cohort of critically ill patients with sepsis. If we can show this is true, independent of other things like age, and comorbidities, then we have something that might be a relevant target for therapy. Our preliminary work suggests that when neutrophils don't or can't produce C1q, they can't be effectively cleared, and thus they continue to promote organ failures and sepsis. We want to both prove that it's prognostically significant, and further investigate the reasons why neutrophil C1q is so important.”

Their work is also a very timely topic as we continue to see COVID cases in hospitals. “A lot of COVID patients,” said Kim, “they don’t really die because of the virus, they die because of the overall inflammation response. It’s not the virus that kills them, it’s what it does to their bodies, and a lot of COVID patients are dying of sepsis.”

Pietropaoli and Kim stress that all of this work is made possible by the enthusiastic assistance of the clinical ICU teams of nurses, respiratory therapists, and providers, and the selfless generosity of their patients and their families.

For the time being, their treatment studies will be conducted with lab mice, providing pre-clinical data that will be used to build rationale for potential human clinical trials down the road. Should their work prove successful, URMC may present the world with a new drug treatment for sepsis.