Last summer, Synairgen quotas soared 300% in a study showing its inhaled form of interferon beta-1a being developed to treat COVID-19, reducing the chance that patients would progress to to a severe form of the virus.
But there was a significant shadow over the results: interferon is known to increase levels of ACE2 protein on the cell surface, which serves as the entry point for SARS-CoV-2, the virus that causes COVID-19. This sparked fears that interferon-based treatments would eventually fail in coronavirus treatment.
Now, researchers led by the University of Southampton, which is collaborating with Synairgen in the development of its drug, have found that interferon raises levels in a short form of ACE2 that prevents the entry of SARS-CoV -2 in the cells. In fact, it can have a protective effect, the team reports in the journal Nature Genetics.
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The short form of ACE2 discovered by researchers in the UK does not have a particular binding site that SARS-CoV-2 needs to enter healthy cells. Because this brief version of the protein increases in response to interferons, but not SARS-CoV-2, researchers believe it is somehow involved in the body’s natural immune response to viruses.
“We were thrilled to discover a new form of ACE2 and became even more interested when we did [realized] this may be protective against SARS-CoV-2 in the airways rather than a site of entry for infection, ”said University of Southampton professor Jane Lucas, MD, Ph.D., in a statement.Two of the study’s co-authors, Donna Davies, Ph.D., and Ratko Djukanovic, MD, are co-founders and shareholders of Synairgen, which was split from the university.
Investors applauded Synairgen when preliminary data from its trial of 101 patients showed that its interferon drug, SNG001, reduced the risk of progression to severe COVID-19 by 79% compared to placebo. An update of these results raised the company’s shares by another 30% in November, when the company reported that 75% of patients taking SNG001 showed clinical improvement on 15/16, as measured by a key scale of the World Health Organization.
The discovery of the short ACE2 could have implications for something more than Synairgen, the authors argued in the new study. The ability of researchers to distinguish between the two versions of the protein could generate ideas for more sophisticated coronavirus treatments, they said.
The team led by the University of Southampton is planning further studies to investigate the implications of the short ACE2 on the management of COVID-19.
In December, Synairgen announced that it had initiated a phase 3 trial of SNG001 in the UK and that the FDA had granted the drug a fast track status and authorized it for studies in the US.