Diseases affecting the joints, muscle and bone, (rheumatic diseases), such as rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA) and psoriatic arthritis (PsA) are chronic, disabling conditions that affect millions of people worldwide. These diseases have no cure and half of the patients do not respond well to available treatments. Therefore, there is a need to identify novel effective treatments for rheumatic diseases. However, identifying novel therapies is difficult because the biological mechanisms that are altered in rheumatic diseases are not completely understood.

Genetic studies can help identify the genes that cause these diseases. This type of study has recently been used in drug discovery programmes. The hope is that by targeting the cause of the disease, any treatments will be more effective than just relieving symptoms. Genetic studies have been successful in finding DNA changes which influence these diseases, but it is still unclear what these changes do. This is because they do not directly affect genes, but lie in non-coding parts of the genome. This was previously known as “junk DNA”. However, we now know that these parts actually have a very important role in turning genes on and off.

In our previous work we looked at how the DNA is folded in the cell. To do this, we used a technique called Capture Hi-C. This allowed us to link these changes, which influence the disease, to the genes they turn on or off for RA, JIA and PsA.

In this study, we have used this information and identified genes which could be involved in these diseases. Using these genes, we searched an online catalogue of currently used drugs, DrugBank, to identify potentially useful drugs which are already used to treat other diseases. These drugs are safe and could be used or ‘repositioned’ to treat rheumatic diseases. We found 367 existing drugs, used to treat other conditions, which could be used to treat rheumatic diseases, including many already in use.

We have shown that by using this approach we can identify existing drugs which could be repositioned to treat rheumatic diseases. This work could identify new ways to treat patients. This will reduce the economic impact on healthcare providers but, more importantly, enhance patient’s quality of life. As we carry out more research in patient samples, we will improve this method and our chances of finding different drugs which could be used to treat rheumatic diseases.

Publication

(Martin P, Ding J, Duffus K, Gaddi VP, McGovern A, Ray-Jones H, Yarwood A, Worthington J, Barton A, Orozco G. Chromatin interactions reveal novel gene targets for drug repositioning in rheumatic diseases. Ann Rheum Dis 2019 May 15;78(8):1127-34
DOI:10.1136/annrheumdis-2018-214649)

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Diseases affecting the joints, muscle and bone, (rheumatic diseases), such as rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA) and psoriatic arthritis (PsA) are chronic, disabling conditions that affect millions of people worldwide. These diseases have no cure and half of the patients do not respond well to available treatments. Therefore, there is a need to identify novel effective treatments for rheumatic diseases. However, identifying novel therapies is difficult because the biological mechanisms that are altered in rheumatic diseases are not completely understood.

Genetic studies can help identify the genes that cause these diseases. This type of study has recently been used in drug discovery programmes. The hope is that by targeting the cause of the disease, any treatments will be more effective than just relieving symptoms. Genetic studies have been successful in finding DNA changes which influence these diseases, but it is still unclear what these changes do. This is because they do not directly affect genes, but lie in non-coding parts of the genome. This was previously known as “junk DNA”. However, we now know that these parts actually have a very important role in turning genes on and off.

In our previous work we looked at how the DNA is folded in the cell. To do this, we used a technique called Capture Hi-C. This allowed us to link these changes, which influence the disease, to the genes they turn on or off for RA, JIA and PsA.

In this study, we have used this information and identified genes which could be involved in these diseases. Using these genes, we searched an online catalogue of currently used drugs, DrugBank, to identify potentially useful drugs which are already used to treat other diseases. These drugs are safe and could be used or ‘repositioned’ to treat rheumatic diseases. We found 367 existing drugs, used to treat other conditions, which could be used to treat rheumatic diseases, including many already in use.

We have shown that by using this approach we can identify existing drugs which could be repositioned to treat rheumatic diseases. This work could identify new ways to treat patients. This will reduce the economic impact on healthcare providers but, more importantly, enhance patient’s quality of life. As we carry out more research in patient samples, we will improve this method and our chances of finding different drugs which could be used to treat rheumatic diseases.

Publications

Martin P. et al. Chromatin interactions reveal novel gene targets for drug repositioning in rheumatic diseases. Annals of the Rheumatic Diseases, 2019;78:1127-1134. DOI:10.1136/annrheumdis-2018-214649 | Publication link: f545b7a3-1d98-44c3-acff-aabb42ef00bc

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