In a new study, researchers have found a new therapeutic target for the treatment of gout, a common type of arthritis that causes episodes of painful and stiff joints.
Their study suggests that blocking a signaling molecule known as TAK1 can suppress inflammation caused by gout.
The research lays the foundation for the development of a new treatment that could strongly improve the quality of life of millions of people around the world who suffer from gout.
The research was conducted by a team at Washington State University and elsewhere.
In the United States alone, gout affects an estimated 8.3 million people or about 4 percent of the population.
Gout is caused by high blood levels of uric acid, a natural waste product from the digestion of foods that contain purines, such as red meat, seafood, dried beans, and beer.
Elevated uric acid levels can lead to the formation of monosodium uric acid (MSU) crystals that accumulate in joints.
The immune system will perceive these crystals as a threat and launch an immune response against them that increases the production of interleukin-1-beta (IL-1-beta), a cytokine protein that causes inflammation and triggers the intense pain and swelling people experience during gout attacks.
The team designed a study to identify the molecular mechanism by which MSU crystals produce IL-1-beta inflammation and the role of TAK1 in this process.
Using two different cell lines of human macrophages—immune cells that play a key role in inflammation—they found that MSU crystals could directly activate TAK1 and other proteins that were previously thought to be dependent on IL-1-beta signaling for activation.
Next, they showed that the use of a chemical that inhibits, or blocks, TAK1 could completely suppress any inflammation caused by MSU crystals, both in healthy human cells and in a rodent model of gout.
The team says their discovery has opened the door towards the development of new treatment strategies for gout.
One current treatment scientists have experimented with is Anakinra, a drug that blocks the binding of IL-1-beta to its receptor.
Though it has shown promise, the drug is not clinically used for gout, because it is given by infusion—which requires hospitalization; its effectiveness is limited, and it comes with a potential risk of infections when used long term.
Developing TAK1 inhibitor drugs that could be taken by mouth would allow patients with gout to manage flare-ups of the disease at home.
The team’s next goal is to confirm their findings in cells taken from patients with gout.
One author of the study is Salah-Uddin Ahmed, a professor of pharmaceutical sciences.
The study is published in the journal Cellular and Molecular Immunology.
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