Chinese Identify Proteins That Could Become Ankylosing Spondylitis Therapy Targets

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by Alice Melao |

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A re-analysis of the genetic landscape of ankylosing spondylitis patients led to Chinese researchers identifying two proteins that may help regulate the disease.

Another finding was that an existing drug called Indocid (indomethacin) might be used to bolster the anti-inflammatory role that one of the proteins plays and to curb the pro-inflammatory role of the other protein.

The findings not only increased understanding of the mechanisms underlying ankylosing spondylitis, but could also lead to new treatment options, the team said.

Their study, “Identification of potential target genes for ankylosing spondylitis treatment,” was published in the journal Medicine.

Ankylosing spondylitis is a chronic inflammatory disease affecting the spine and joints. It is commonly treated with drugs that target the immune system and its pro-inflammatory signals, such as interleukin and TNF inhibitors.

Scientists have learned more about the cell mechanisms behind the progression of ankylosing spondylitis and how to deal with them. But responses to treatments have varied from patient to patient, and researchers still need to know more about what drives the disease.

Trying to find additional mechanisms that contribute to ankylosing spondylitis, Chinese researchers re-analyzed genetic data collected from 16 patients and 16 healthy controls they  had obtained in a previous study. They analyzed patients’ blood samples with whole genome sequencing, which gave them an overview of the genetic landscape of ankylosing spondylitis.

The team used different computational analysis strategies to try to find potential ankylosing spondylitis therapy targets. They identified 136 genes that were more abundant in ankylosing spondylitis samples than in controls, and 198 that were less expressed.

They also found seven transcription factors and 14 microRNA molecules that played a role in the genes’ regulation and 215 proteins that appeared to be involved in the mechanisms underlying ankylosing spondylitis.

Combining all the genetic, regulatory, and protein-interaction profiles, the team identified six drugs that might be able to counteract many of the molecular changes related to ankylosing spondylitis. These were methotrexate, Azulfidine (sulfasalazine), Indocid (indometacin), diclofenac, ibuprofen, and Aredia (pamidronate).

Two proteins that help regulate inflammatory signals showed promise as therapy targets —  the MAPK7 enzyme and the NDUFS4 mitochondrial protein.

Researchers said MAPK7 may function as an anti-inflammatory agent in the progression of ankylosing spondylitis, while NDUFS4 may contribute to the disease’s progression.

Importantly, the team reported that Indocid, a non-steroid anti-inflammatory drug, could might be able to change the two proteins’ behavior. It would do this by enhancing MAPK7’s  activity and blocking NDUFS4’s activity.

Further studies are necessary to confirm the findings, including the proteins’ roles in ankylosing spondylitis, the team said.