Genetic discovery could herald new rheumatoid arthritis drugs

A group of genes linked with a heightened risk of rheumatoid arthritis have been discovered in a new study, reshaping understanding of what causes the disease and pointing to possible treatments.

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Scientists found 16 genes associated with the painful condition, with six in particular producing proteins known as immune checkpoints. When these proteins malfunction, the immune system can over-react and attack the body’s own cells. 

Experts say that targeting the checkpoints with drugs could treat or even cure people with rheumatoid arthritis, a disease which causes pain, swelling and stiffness in joints for 400,000 people in the UK.

Core genes

To pinpoint the core genes for rheumatoid arthritis, researchers from the University of Edinburgh looked at genetic data from 450,000 individuals in the UK Biobank. They used a new approach to add up the small effects of hundreds of common mutations on each gene.

The main core gene they identified produces an immune checkpoint called programmed death protein 1 (PD-1). 

Drugs that target the protein to prevent the immune system over-reaction have proved effective in treating rheumatoid arthritis in recent trials, though these drugs are not yet licensed for use in patients. 

The research team will now study whether the activity of these core genes can help guide treatment decisions for people with the disease.

Combined effect

Previous genetic studies have identified specific differences in the DNA of people with and without the condition, but studying genes near these mutations has failed to discover new treatments. 

Recently, scientists proposed that small changes in many genes could combine to affect a few core genes directly linked with the disease. Experts say this helps explain why genes found in earlier studies are not the best drug targets as they affect the main genes but do not directly cause the disease.

This work reshapes our understanding of the causes of rheumatoid arthritis. We expect drugs that target the causes of the disease to be more effective than the drugs used now, which only target inflammation. We’re encouraged by the promising results of trials of drugs that target PD-1 in rheumatoid arthritis. Our research can help identify which other autoimmune diseases these drugs are likely to be effective in.

The study was funded by the UK Medical Research Council and also involved researchers from the University of Manchester and Queen Mary University London. 

Related links

Read the study in the journal Arthritis and Rheumatology

Usher Institute

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