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Anti-STING Therapy for Rosacea?

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STING crystal structure created by PDB protein workshop rendering PDB: 4EMU
Image courtesy of Wikimedia Commons - Wikipedia

"Here we report the discovery and characterization of highly potent and selective small-molecule antagonists of the stimulator of interferon genes (STING) protein, which is a central signalling component of the intracellular DNA sensing pathway." [1]

There is a theory that rosacea is a disorder of the innate immune system. In a recent article published In Nature, Targeting STING with covalent small-molecule inhibitors, [1] scientists at the Ecole Polytechnique Fédérale de Lausanne [EPFL] have discovered two small-molecule compound series that can effectively block a central pathway of the innate immune system. "STING plays an important role in innate immunity." [2] "To find out the compounds' mechanism of action, the researchers painstakingly mutated several of the amino acids that make up STING in order to find out which ones are targeted by the compounds. Doing so, the scientists identified a conserved transmembrane cysteine, which binds to the compounds irreversibly. As a consequence of this interaction, this particular cysteine residue can no longer undergo palmitoylation - a post-translational modification that attaches a fatty acid (palmitic acid) to STING." [3]

Andrea Ablasser, Assistant Professor at EPFL, explains, "“Our work uncovered an unexpected mechanism to target STING and provided the first proof-of-concept that anti-STING therapies are efficacious in autoinflammatory disease. Beyond specific monogenic autoinflammatory syndromes, the innate immune system is implicated in even broader ‘inflammatory’ conditions, so we are excited to learn more about the role of STING in human diseases.” [4]

The Nature article concludes, "In summary, our work uncovers a mechanism by which STING can be inhibited pharmacologically and demonstrates the potential of therapies that target STING for the treatment of autoinflammatory disease." [1] This may hold some hope for an 'Anti-STING Therapy for Rosacea." 

Independent Rosacea Research
Could a group of rosacea sufferers in a non profit organization like the RRDi collectively get together and sponsor their own research on rosacea? For example, if 10K members each donated a dollar, could it be possible that this money could be used to sponsor their own independent rosacea research on a anti-sting therapy?  What do you think? If you want to do something about this read this post

End Notes

[1] Nature, Letter, Published: 04 July 2018
Targeting STING with covalent small-molecule inhibitors
Simone M. Haag, Muhammet F. Gulen, Luc Reymond, Antoine Gibelin, Laurence Abrami, Alexiane Decout, Michael Heymann, F. Gisou van der Goot, Gerardo Turcatti, Rayk Behrendt & Andrea Ablasser 

[2] Stimulator of interferon genes (STING), Wikipedia

[3] New small molecules offer promising new way to treat autoinflammatory diseases, News Medical, Life Sciences, July 4, 2018

[4] New small molecules for the treatment of autoinflammatory diseases, EPFL News, July 4. 2018

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More has been uncovered in a report published in Cell Reports, April 7, 2020 by Balka et al. who report, "We further demonstrate that TBK1 acts redundantly with IkB kinase ε (IKKε) to drive NF- kB upon STING activation."  While this may be daunting to understand for a layman, James Ives, News Medical Net, explains the significance of this, "The two signalling arms of the cGAS-STING pathway were thought to be mediated by a single upstream kinase, TANK binding kinase (TBK1)...."That basically told us that the mechanism that drives the second cytokine pathway depends on both proteins, but that they act redundantly - if one's missing the other one does the job,"..." 

Read the clinical paper below: 


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