Nitro-fatty acids — a type of fatty molecule naturally produced in the body — could act as natural inhibitors of the stimulator of IFN genes (STING), a protein involved in inflammatory diseases such as systemic lupus erythematosus (SLE), according to a study.
The study, “Nitro-fatty acids are formed in response to virus infection and are potent inhibitors of STING palmitoylation and signaling,” was published in the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS).
STING is a key molecule of the immune system that responds to viral infections by increasing the number of interferons (IFN) and other inflammatory molecules that activate immune cells.
In some cases, however, STING causes an overproduction of these inflammatory molecules. This contributes to diseases including SLE and Aicardi-Goutières syndrome, a disease that mostly affects the brain and skin. STING also is a stimulator of IFN gene-associated vasculopathy with onset in infancy (SAVI) — abnormal inflammation involving the skin, blood vessels, and lungs.
Treatments for STING-related diseases are limited, and researchers have long been searching for a molecule that could inhibit STING activity. Now, a team in Denmark, along with colleagues in Germany, Japan, the United States, Canada, and United Kingdom, have discovered nitro-fatty acids, which have the ability to block STING.
Nitro-fatty acids are modified lipid molecules with anti-inflammatory properties, naturally produced by the body as a response to viral infections. According to the study, the molecules can regulate STING activation and apparently act as STING inhibitors.
Researchers tested the action of nitro-fatty acids in cells from SAVI patients. They found that the lipid molecules were able to control STING by directly interacting with and modifying it. The modified protein was unable to trigger type I interferon production and inflammation was reduced.
SAVI causes abnormal inflammation throughout the body and starts affecting patients in the first months of life. Treatment options are limited. But the results of the study indicate that nitro-fatty acids can serve as the base to develop a therapy to treat the disease.
“Our results bring hope that we can develop effective medicine for the affected children. We also hope that the discovery can be of significance for the treatment of lupus, which is an inflammatory disease of the connective tissue, where STING also plays a role,” Christian Holm, an associate professor in the Department of Biomedicine at Aarhus (Denmark) University and co-author of the study, said in a press release.
Becasue nitro-fatty acids are naturally produced by the body, they might present fewer secondary effects than a treatment derived from artificial substances. The acids are currently under Phase 2 clinical testing as a treatment for focal segmental glomerulosclerosis and pulmonary hypertension (NCT02460146 and NCT02313064). So far, patients have tolerated them well.
More research is needed to develop an effective therapy, but researchers think their findings have “considerable medical potential, as [nitro-fatty acids] might either be used directly as [anti-inflammatory] drugs or be used as a tool for designing highly efficient drugs that specifically target STING.”