More Therapeutic Ideas for the Coronavirus: Too Much Inflammation? – Science Magazine

So today Id like to talk about some of the other anti-coronativirus possibilities that I havent gone into yet these posts will never make a comprehensive list, but at least I can cover some of the more interesting ideas, I hope.

Interleukin-6 is an interesting story. This preprint from German researchers presents some evidence that IL-6 levels correlate with the likelihood of severe respiratory symptoms in coronavirus-infected patients: the more IL-6, the worse the outlook. That makes sense, because the protein is already well-established as a big player in immune and inflammation pathways. The question is whether in some patients the immune response gets out of hand; theres a very real chance that many of the worst outcomes are as much a problem with a patients reaction to the viral infection rather than the infection per se. There were early indications of this in the epidemic; this is the cytokine storm that you hear about so much these days, and the remedy for such a situation is to try to turn the immune signaling back down.

Anti-IL-6 antibody therapies have been developed for just that purpose, for patients with autoimmune disorders who need to turn the dial down in just that manner. Rheumatoid arthritis patients generally have elevated IL-6, for example, and tocilizumab (brand name Actemra) was approved by the FDA in 2010 as a therapy. Its since picked up other indications, such as use in cytokine release syndrome, a similar over-stimulation that can show up as a complication in the new CAR-T engineered T-cell therapies for cancer. So its use in the current epidemic seems like a reasonable idea. Its been approved for that purpose in China, there are anecdotal reports from there, from Italy and from other areas, and there are trials underway or planned in China, Switzerland, the US, Belgium, Greece, and Denmark at the very least. Theres another anti IL-6 antibody that was approved in 2017 (sarilumab, brand name Kevzara), and that one is also going into coronavirus trials.

Update: via the comments, there also siltuximab (brand name Sylvant), an antibody which targets the IL-6 protein itself rather than receptor, as the two above do. Its also being looked at in the clinic, and itll be interesting to see if there are different effects, since some of these proteins have functions beyond those mediated by their receptors.

A similar possibility is anakinra (brand name Kineret), which targets the IL-1 system. Interleukin-1 is also a big player in the immune response, and unraveling its complexities is an ongoing project, since there are 11 related interleukins in that family (isnt immunology great?) But they generally work through a limited set of IL receptors, and theres even a natural antagonist protein (IL-1R) that blocks one of them. Anakinra is a modified version of that antagonist, and its also in trials (in fact, its an arm of some of the same trials investigating the IL-6 antibody).And there are other ways to target the response. Heres a proposal to use antagonists of the alpha-1 adrenergic receptor such as prazosin, and heres oneto try low-molecular weight heparin. Sphingosine kinase 2 is involved in inflammation signaling, and an investigational inhibitor of the enzyme (opaganib) is being tried in Italy. Ruxolitinib (brand name Jakavi) is a Janus kinase inhibitor that also affects these pathways and is being looked at as well. Theres even a technique to filter out such signaling molecules from the blood thats getting a look.

Obviously turning down the inflammation response if there arent signs of overstimulatory trouble would (youd think) be a bad idea. Many of these drugs carry warning labels on them already about not using them during acute infections or noting that they can increase the risk of one. But if overstimulation of the immune response really is the problem, this approach could be just whats needed. Picking out the patients that will benefit will be the tricky part!

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More Therapeutic Ideas for the Coronavirus: Too Much Inflammation? - Science Magazine