Could a New Type of Medicine Help People with Rheumatoid Arthritis?

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Image credit: https://openai.com/index/dall-e/

Rheumatoid arthritis (RA) is a condition where the body's immune system attacks its own joints, causing pain, swelling and difficulty moving. It's a long-term illness, and currently, there isn't a cure. But what if we could find a way to 'reprogram' the cells that cause this inflammation, without changing the person's actual DNA? That's where a new area of research, called epigenetics, comes in.

Understanding epigenetics: Imagine your DNA as a cookbook, containing all the instructions for your body. Epigenetics is like the notes and bookmarks you add to that cookbook; they don't change the recipes themselves, but they can affect how they're used. In RA, some of these 'notes' cause the immune cells to become overactive, leading to inflammation.

Histones and their role: One important part of epigenetics involves structures called histones. Histones are proteins that act like spools that DNA wraps around. The way the DNA is wrapped can affect how easily the genes can be read and used. Enzymes called histone acetyltransferases (HATs) and histone deacetylases (HDACs) control this wrapping by adding or removing chemical tags called acetyl groups. When there are more acetyl groups attached, the DNA is more easily read and expressed.

Targeting histone acetylation: Scientists are exploring whether they can use drugs to change these epigenetic 'notes'. The aim is to calm down the overactive immune cells and reduce inflammation in RA. This could be done by targeting the enzymes that modify histones.

A new study: In a recent study, researchers looked at 25 different drugs that could affect these histone-modifying enzymes. These drugs targeted different enzymes, including HAT inhibitors: These stop HATs from adding acetyl groups, HDAC inhibitors: These stop HDACs from removing acetyl groups and BET inhibitors: These prevent certain proteins from binding to acetylated histones.

The study involved taking blood samples from both healthy people and people with RA. The researchers tested the drugs on immune cells from these samples. They then used special techniques to look at how the drugs affected the cells, including which genes were being expressed.

What the study found: The researchers found that the drugs could change the way immune cells behave. They also found that some drugs were better than others at reducing inflammation. Here are some of the key findings:
  • Some drugs had a greater impact on specific cell types such as monocytes and NK cells.
  • The effects of the drugs depended on their concentration.
  • Drugs that targeted histone acetylation (HDAC inhibitors, HAT inhibitors and BET inhibitors) had the greatest impact on gene expression, especially in areas related to the immune system.
  • Some of the drugs, like Ricolinostat, showed effects that were similar to existing RA treatments.

Specific HDAC inhibitors: The study found that drugs targeting HDAC6 (a specific type of HDAC) were especially promising. These drugs could reduce inflammation while having fewer side effects than drugs that block all HDACs.

What does this mean for people with RA? This study shows that epigenetic drugs, particularly those affecting histone acetylation, could be a new way to treat RA. These drugs could help to reduce inflammation, rebalance the immune system and potentially have fewer side effects than existing drugs.

Next Steps: While this research is promising, there is still more work to do. Scientists need to test the drugs in larger studies, develop more specific drugs with fewer side effects and conduct clinical trials to see if these drugs are safe and effective for people with RA.

Conclusion: Epigenetics is opening up new possibilities for treating RA, and drugs that modify histone acetylation are a promising avenue. With further research, these findings could lead to new treatments that could greatly improve the lives of people with RA. This study highlights the potential for using targeted epigenetic drugs to calm the immune system and reduce inflammation without changing a patient's DNA.
It is worth noting that the sources are from a scientific study and not all the findings have been fully verified in clinical trials, which is something that would need to happen before these sorts of treatments would become available to patients.
 
Additional information: Targeting histone acetylation enables epigenetic modulation of inflammatory pathways, a novel therapeutic strategy for rheumatoid arthritis. BioRxiv (2025). https://doi.org/10.1101/2025.01.14.632975

Journal information: https://www.biorxiv.org/


Location: Oxford, UK

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