. SCIENTISTS have isolated the protein responsible for causing arthritis.
They say the breakthrough will make it easier to develop drugs to combat the agonising condition.
It could also lead to cures for a host of other chronic problems, including inflammatory bowel syndrome, Crohn’s disease and psoriasis, which together affect more than 11 million people in Britain.
The protein, known as MLKL, triggers a process called necroptosis. When a cell is infected by a virus or has become too old to serve a useful purpose it usually self-destructs causing no harm to the rest of the body.
But in necroptosis the dying cell sends a message to the immune system telling it something has gone wrong and instructing it to mount a response by producing inflammation.
Scientists believe these messages lead to the development of inflammatory diseases such as arthritis. And, according to Australian researchers, it is the MLKL protein that starts the whole process off. Dr James Murphy, of the
Walter and Eliza Hall Institute of Medical Research in Melbourne, said: “This study provides the first genetic proof that MLKL is required for necroptosis.
“These discoveries are really exciting because they give us a new target to look at for developing treatments for people who suffer from an inflammatory disease.”
Dr Murphy, whose findings are published in the journal Immunity, added: “We discovered that MLKL needs to be switched on before it can activate necroptosis.
“MLKL could therefore be a perfect target for treatments because it is different from almost every other cell-signalling protein, making it easier to develop highly specific drugs and limiting potential side effects.”
Associate Professor John Silke said: “We are now trying to work out what MLKL looks like at the atomic level so we can begin to develop drugs that will block it.
“We are excited about this fundamental discovery and are already using this knowledge to develop specific, drug-like molecules to test in disease models. This could lead directly to treatments that will help patients who have chronic inflammatory diseases including rheumatoid arthritis, inflammatory bowel syndrome, Crohn’s disease and psoriasis.”
Professor Anisur Rahman, of Arthritis Research UK, said: “Under some conditions the necroptosis pathway is activated inappropriately, causing inflammation and potentially contributing to the development of inflammatory diseases such as rheumatoid arthritis.
“This study sheds new light on the process of necroptosis by suggesting a key role for the protein MLKL.
“A thorough understanding of the causes of inflammation, including necroptosis, is important to allow the development of new and effective treatments for inflammatory arthritis. Further work is now required to investigate the role of MLKL.”
Dr Jeremy Sanderson, consultant gastroenterologist at Guy’s and St Thomas’ Hospital, London, said: “This work looks exciting and we always welcome new developments that offer further insights into the complex pathways of the inflammatory bowel diseases, Crohn’s disease and ulcerative colitis.
“Gaining greater understanding of the molecular jigsaw puzzle surrounding Crohn’s and colitis is vital but the other factors such as the role of genetics must also be considered.”
By: Giles Sheldrick
express.co
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