Transgenic Mouse That Models Immune Disease’s Cytokine Storms Could Point to Treatment Solution for COVID-19

By HospiMedica International staff writers
Posted on 05 Jun 2020

A transgenic mouse developed at Cincinnati Children’s Hospital Medical Center (Cincinnati, OH, USA) to model the deadly childhood immune disease HLH (hemophagocytic lymphohistiocytosis) could play a key role in saving lives during the COVID-19 virus pandemic.

The so-called cytokine storm that inundates the bodies of severely ill COVID-19 patients with inflammatory cells produced by the immune system is a common feature of children battling secondary HLH, which happens in patients where initial HLH treatment has not worked. This common clinical feature of both illnesses was noticed by Gang Huang, PhD, one of the inventors of the genetically engineered mouse strain and a cancer pathologist at Cincinnati Children’s. He also noticed that severe COVID-19 disease clinical manifestations are very similar to those seen in transgenic laboratory mice created to faithfully mimic human secondary HLH in the lab. That preclinical laboratory research, some of it in collaboration with researchers in Wuhan, China, helped identify the drug ruxolitinib for treating secondary HLH. The anti-inflammatory drug is also used to treat other blood diseases, including leukemia.

Image: This is a microscopic photo of a blood smear from a transgenic mouse that mimics the human immune disorder, secondary HLH (Photo courtesy of Cincinnati Children’s Hospital Medical Center)

During their work, Huang and researchers in China found other clinical studies involving other diseases where ruxolitinib also had worked well at quieting inflammation, and proceeded to successfully test the drug which dramatically reversed respiratory and multi-system inflammation in severely ill COVID-19 patients. A larger Phase III clinical trial RUXCOVID by Incyte and Novartis is now testing up to 400 severely ill COVID-19 patients with ruxolitinib, according to Huang, and preliminary clinical data from the study is expected during the summer.

“This is the first therapy we know of that appears to work effectively to quiet the cytokine storm and inflammation in severe COVID-19 disease, and there are no significant toxicities to patients who take the drug by two pills a day,” said Huang. “This is critical until we can develop and distribute enough effective vaccine to help prevent people from becoming infected.”

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Cincinnati Children’s Hospital Medical Center