Researchers in Dublin have led an international study identifying a remarkable drug that may be able to block major diseases such as multiple sclerosis (MS), alzheimer’s, rheumatoid arthritis and most other inflammatory conditions.
Initial tests show it could instantly block MS and the effects of blood poisoning in mouse models. It also halted a rare inflammatory disease called Muckle-Wells syndrome using human blood samples as a test.
Muckle-Wells syndrome is a disorder characterised by episodes of skin rash, fever and joint pain. Progressive hearing loss and kidney damage also occur with this illness.
The drug, called MCC950, stops a very early trigger that sets off the inflammatory response to infection. While inflammation is good during infections it can cause a wide range of serious diseases if the inflammation remains in place.
“This is exciting, one of the biggest discoveries we have had,” said Prof Luke O’Neill, the chairman of biochemistry based in the Trinity Biomedical Sciences Institute. “It is fantastic, the thing we have been looking for for 30 years. This could be the missing compound.”
Their main discovery is being able to identify the pathway that allows the drug to block the action of a pro-inflammatory substance in the body called NLRP3.
They also confirmed that inflammatory diseases all share a common process, even though the parts of the body becoming inflamed might differ, he said.
This was shown in the treatment of three very different conditions in mice and also when using human samples. “It really showed that it could work in humans,” he said.
Trinity’s collaborators included the Universities of Queensland, Michigan, Massachusetts and Bonn and their findings were published on Monday in the journal Nature Medicine. He was co-senior author with Prof Matt Cooper of Queensland, and lead author was Dr Rebecca Coll who worked with Prof O’Neill.
Pharmaceutical giant Pfizer developed the original compound about 20 years ago, said Prof O’Neill. It knew the drug was anti-inflammatory but it could not establish its “pathway”, how it actually worked.
“It was serendipity. I knew they had an interesting drug back in 2001 and I wondered if it targeted the pathway we were looking at,” he said.
The drug formula was in the public domain and he asked Prof Cooper if he would make the drug so it could be studied and tested in Dublin.
“The results began to roll in, it was one of those rare occasions where everything we did seemed to come out positive,” said Prof O’Neill.
It “worked wonders” in curing mice of MS and in blood poisoning where the entire body becomes inflamed. “That really told me we have a common pathway for all of these diseases.”
This was further confirmed when it stopped Muckle-Wells syndrome using human blood cells from affected patients. “This could be the first disease to be cured in humans using the drug.”
It may not cure all conditions but it would certainly halt their progression, he said. “It is the escalation of those diseases that cause all the problems,” he said.
He and Prof Cooper are considering setting up a company to develop the drug further. “We seem to have got there first with a small molecule that can block inflammation.”
Prof Cooper has compounded several unique forms of the drug based on the original formula and these can now be patent protected.
Funding came from Science Foundation Ireland and the European Research Council.