New discoveries in the battle against arthritis

Researchers are getting closer to what initiates the disease process in arthritis and to developing new drug treatments.

The mystery surrounding arthritis is gradually being unravelled and with a deeper understanding of the disease comes the potential for new therapies. Importantly, many new discoveries relating to the disease are being made here in the Republic.

One of the country’s top arthritis researchers provided a 20-year look-back at the disease in a public lecture that described the work being done here and elsewhere to understand what triggers this debilitating affliction. Prof. Luke O’Neill, head of the Department of Biochemistry at Trinity College Dublin, delivered an engaging talk on the subject last Thursday to a large audience at the Royal Dublin Society’s concert hall in Ballsbridge. O’Neill studies the biochemical triggers that produce the joint inflammation seen with arthritis. Appropriately, the talk carried the title, ‘Arthritis, how close are we to a cure’, an approach that allowed him to track the progress being made in understanding its causes and in the development of new drugs against it.

The talk was organised jointly by The Irish Times and the RDS in association with the Irish Society of Immunology (ISI). Each year the Society honours one of its best researchers with an award given in recognition of work that contributes to a better understanding of immunology. Prof. O’Neill is this year’s ISI award winner and so was invited to deliver the lecture.

“I have worked on arthritis for the past 20 years or so at various levels,” Prof. O’Neill says. He worked with patients as a young researcher and in more recent years in the lab focusing on the disease in which joints become inflamed to produce pain. In some cases the arthritis is provoked by the body’s own immune system. “That is what happens in arthritis, you get a deregulation in the inflammation process caused by the immune system,” Prof. O’Neill explains. “The immune system is central to the development of arthritis.”

There are two forms of the disease, rheumatoid arthritis and osteo-arthritis, with the former involving aspects of the immune system. Both, however, are characterised by inflammation in the joints. “In rheumatoid arthritis the joint is chock-full of immune cells,” says Prof. O’Neill. His goal is to understand “what is going wrong in the immune system with arthritis”, what is triggering the inappropriate immune-cell invasion and the release of inflammatory substances that follow it.

“It could be that all rheumatoid arthritis is triggered by an infectious agent, but we haven’t found it yet,” he says. Infection by the bacterium that causes Lyme disease is known to cause joint inflammation. The problem is that if an infection actually is the trigger the agent that caused it is usually long gone by the time that joint inflammation sets in. “That is why people have had so much trouble tracking down the infectious agent,” explains Prof. O’Neill.

Whatever the trigger, the result is that the immune system “begins to see the body’s own tissues as foreign”, he says. It launches attacks against certain tissues, in turn causing the joint inflammation seen in arthritis. “What we do know now is we know the (immune) cells involved in joint inflammation and the chemicals these cells are making,” he explains. “People are designing drugs to target these chemicals.”

Prof. O’Neill’s own research has continued along a single route from the beginning. “My goal has always been to get to the start of the arthritis process.” The work has taken him step by step further up the cascade of events that lead to an arthritic outcome. “We now know what is driving the cytokines, they are known as toll-like receptors. We are getting closer to what initiates the disease process,” he says.

The work has also encouraged him to establish a campus company, Opsana Therapeutics, which will allow him to commercialise discoveries being made at Trinity College. “Academic research ultimately should be translated into the commercial world,” he says.

Thursday, 28 October 2004
Professor Luke O’Neill

TCD School of Biochemistry and Immunology: http://www.tcd.ie/Biochemistry/