FEB 27, 2024 11:00 AM PST

Popular asthma drug treats rheumatoid arthritis

WRITTEN BY: Amielle Moreno

Rheumatoid Arthritis (RA) is a challenging autoimmune disease affecting millions worldwide. A 1992 clinical trial found that the asthma drug Zileuton alleviated RA symptoms, but the promising results did not lead to FDA approval. A recent paper in Science Signaling could reinvigorate efforts for FDA approval by identifying the mechanism behind Zileuton's effects on RA.

RA involves the immune system attacking the body's own tissues, with a key aspect being the inflammation of the synovium, the soft tissue lining the spaces around joints and tendons. The paper's findings shed light on a previously overlooked aspect of the disease's pathogenesis by delving into the role of pyroptosis—an inflammatory type of programmed cell death—in RA progression.

First, the study identified pyroptosis of CD4+ T cells in the blood as a "major effector cells of abnormal immunity in patients with RA." This cell death process releases inflammatory signals, exacerbating synovitis.

MorScience CC by 3.0

Second, a transcriptional analysis of T cells from RA patients revealed over 50 with altered expression in RA CD4+ T cells, including the upregulation of the gene for an enzyme called arachidonate 5-lipoxygenase (ALOX5). Mapping the cascade of molecular events associated with ALOX5, the researchers detailed precisely how the enzyme enacts its pyroptotic effects.

Third, the study identified ALOX5 as a significant factor in CD4+ T cell pyroptosis, with high levels of ALOX5 associated with more severe RA symptoms. In patient populations, low levels of ALOX5-containing T cells were associated with disease remission.

Finally, treating a humanized mouse model of RA with Zileuton inhibited ALOX5, reducing CD4+ T cell pyroptosis, inflammation, and synovial inflammation.

There's little to no evidence why Zileuton's asthma applications took priority over further testing and FDA approval for RA. The findings of this study likely explain the pharmacological effects of Zileuton on RA back in 1992 and suggest that other ALOX5-associated proteins are potential therapeutic targets for managing this autoimmune condition.

Sources: Journal of Rheumatology, CDC, Science Signaling

About the Author
Doctorate (PhD)
Amielle Moreno earned her doctorate in neuroscience from Emory University and has dedicated her career to science communication, news coverage, and academic writing/editing. She is a published researcher who has branched out to author articles for various science websites. She recently published an original research article detailing her findings on how sensory areas of the brain respond to social sound. When she's not writing or editing, you can find her spinning the latest neuroscience news into comedy gold, hosting her podcast "Miss Behavior Journal Club." This fortnightly humorous podcast features the latest in behavioral research. Her goal in life is to defend and discover scientific truths.
You May Also Like
Loading Comments...