UCSD Researchers: Molecule, Via Cancer Drug, Can Prevent COVID-Related Organ Damage

A molecule that helps cancer cells survive could be used to prevent irreversible organ damage from infectious diseases such as COVID-19, researchers said this week.

Published in Science Translational Medicine, the researchers’ work showed the molecule “can be suppressed with a repurposed cancer drug,” according to a news release on Wednesday.

The finding also “represents a new approach” in stopping organ damage in methicillin-resistant Staphylococcus aureus, also known as MRSA, UCSD said.

Researchers first identified the molecule 12 years ago, and discovered it helps cancer cells survive by moving damaging inflammatory cells into tumor tissue,” UCSD announced.

Myeloid cells and an enzyme known as PI3K gamma are factors in that transfer. Myeloid cells are a factor in the immunity humans are born with before being exposed to environmental pathogen, and work swiftly to kill deadly viruses like SARS-CoV-2, which causes COVID-19, according to UCSD.

The research “shows that drugs that can prevent the recruitment of damaging myeloid cells into tissues that are infected with severe agents like COVID-19 or MRSA have a significant benefit in preserving tissue function if given early enough in an infection,” said Judith Varner, professor in the Departments of Pathology and Medicine at the UCSD School of Medicine.

Myeloid cells offer protection, but also do a lot of damage, said Varner, a senior author of the study and co-leader of the Solid Tumor Therapeutics program at UC San Diego Moores Cancer Center.

“If you have a little infection, myeloid cells come in, kill bacteria, release alerts that recruit even more potent killer immune cells and produce substances that can heal the damage,” Varner explained.

“But if you get an infection that’s too strong, you get overproduction of these alert signals, and the substances they release to kill these infective agents can also kill yourself. That’s what happens in COVID- 19.”

PI3K gamma allows myeloid cells to move into cancerous tissues, researchers learned in 2012. New findings show that PI3K gamma “also helps move myeloid cells into tissues infected with SARS-CoV-2,” according to UCSD. Researchers believe that the cancer drug Eganelisib, which inhibits PI3K gamma, might also be effective in subduing COVID-19 inflammation by suppressing the PI3K gamma enzyme’s ability to move myeloid cells into infected tissue.

In a test using the drug, “We sequenced COVID-19 patient lung tissue and showed that when patients have COVID-19, a lot of their lung cells are killed, and there’s a huge increase in myeloid cells,” Varner said. “We also found the same thing in infected mice.

“When we treated with the drug, we showed that Eganelisib prevents entry of myeloid cells into tissue, so they can’t do all that damage,” Varner said. “Further studies will determine if it can actually reverse damage.”

The research team also discovered the same results in mice infected with MRSA, UCSD reported. “Our work is significant because this is the first time this particular approach of targeting the myeloid cells specifically has been shown to be effective in COVID,” Varner said. She added that other drugs tested during the COVID-19 crisis were modestly successful.

The U.S. Food and Drug Administration fast-tracked Eganelisib for development in 2020, but has not approved it for treatment, according to UCSD.

Varner said she hopes the new findings will inspire drug manufacturers to consider making other inhibitors to treat infectious diseases. “We hope that this research will help us obtain funding to continue investigating this approach in other disease settings,” she said.