Commercial Profile - Science Foundation Ireland:Ireland is fourth in the world in terms of the prevalence of asthma. A parasitic worm could hold the solution to this statistic, says Prof Padraic Fallon

WITHIN THE next five years research being carried out by a team at the Institute of Molecular Medicine in Trinity College Dublin could result in the development of new drugs for the treatment of asthma and other auto-immune conditions such as rheumatoid arthritis. And a key role in this Science Foundation Ireland (SFI) funded research has been played by a parasitic worm known as schistosoma mansoni.

While the jump from a normally harmful or pathogenic worm to a treatment for a debilitating and potentially life-threatening illness may appear quite large at first sight, it’s not actually that great when it is explained by Prof Padraic Fallon, who leads the research and heads up the Inflammation and Immunity Research group at the Institute.

“The research really started by asking why developed societies experience an explosion in immunological-related diseases like asthma,” he says. “Thirty years ago it was relatively rare to meet children with asthma. Now if you go to a sports event up to one third of the children there will have inhalers. Ireland is now fourth in the world in terms of the prevalence of asthma and we have to ask ourselves why this is the case.”

Around 470,000 Irish people suffer from asthma and Irish adults with the condition lose an average of 12 days from work each year while up to 24,000 bed days a year are used to treat patients admitted due to asthma.

He says that part of the reason for Ireland’s undesirably high ranking is genetic predisposition – we’re just unfortunate that quite a few of us are prone to the condition. But a lot more of it is due to environmental factors.

“One hundred years ago the way we lived was very different,” he points out. “We didn’t have air conditioning, we didn’t have carpets everywhere and we didn’t have antibiotics to treat diseases. Going back further to a few thousand years ago we were living out on the savannah or in caves and diseases and other pathogens were a fact of life.

“Now, thanks to modern medicine, we are free of many of the pathogens that we evolved with.”

And this is what led him to parasitic worms. “Sixty years ago one third of the world’s population had parasitic worms, today we don’t have worms in the western world. And if you go to Africa or Asia or places where they do have worms you will find a much lower prevalence of these allergic conditions. The presence of the worms there changes the immune system in ways that prevent allergies.”

Having established this link Fallon and his team then set about creating models to mimic what happens in humans with worms. “We were looking for the mechanism or the process that somehow protects against allergies.”

The idea that having worms could somehow be good for us may sound a little far-fetched but it is not all that strange when we consider the role that bacteria play in human life. The human body contains about 10 times as many bacteria as it does human cells and they play a vitally important role in our various physiological and metabolic functions. It should, therefore, come as no surprise that worms may play a similar role.

“Bacteria are part of our evolutionary origins and so are worms. Worms play a role in the education of the immune system and if the system is not educated we get inflammation and diseases that we shouldn’t get. There is a whole range of things about modern living which is totally different to the way we lived 3,000 years ago. This is part of the reason why we are getting all these diseases now. The modern immune system is a by-product of evolution and pathogens had a role to play in that.”

In other words, having worms builds up our immune systems in ways that we haven’t previously understood and our advanced hygiene and healthcare systems in the western world are actually robbing us of this education to our immune system and making us more vulnerable to certain allergic conditions.

The big breakthrough came in the past month when Fallon’s team, in collaboration with Dr Andrew McKenzie from the Medical Research Council Laboratory for Molecular Biology in Cambridge, identified a previously undiscovered white blood cell, called the nuocyte that is involved in allergic responses. The discovery has implications for the development of new treatments of asthma and other allergic diseases.

The new cell was discovered by using the parasitic worms to experimentally drive allergic-like responses. The cell produces a chemical called Interleukin 13 (IL-13) and initiates the early generation of responses that can lead to asthma or other allergic conditions. The name nuocyte, is from nu the 13th letter of the Greek alphabet, reflecting the cell as a major source of IL-13.

“We are very excited to have identified a new cell type that initiates the generation of allergic immune responses that leads to conditions such as asthma,” says Fallon. “Its discovery opens novel opportunities for developing drugs for allergic diseases. This development also sheds new light on the response to parasitic infections and could provide insights into poverty-related diseases worldwide.”

He describes the cell as being the first step in a cascade-type reaction that leads to inflammation. “We want to find the pathway to this inflammation and then find how to suppress it. We will look at the cells in humans in more detail to see if it is part of different conditions and see how it causes inflammation. After that we will see if we can therapeutically change its function. This will involve the development of new drugs.”

This is what makes this discovery so important. “All of the therapies in use for allergies at present don’t take account of the nuocyte cell,” Fallon explains.

“Now with the discovery of the cell we can develop targeted therapies to treat the inflammation at source rather than just the symptoms. It is a very significant breakthrough.”

He is quick to credit the role of Science Foundation Ireland in this breakthrough. “The number of major discoveries in medicine that researchers from Ireland have published in international journals over the past number of years has been very significant and this would have been impossible without the support of SFI,” he says.

“SFI is playing a very important role in helping Ireland compete at the top level in international research.”

He believes that we will see the benefits of this latest breakthrough within the foreseeable future.

“I would say that within the next five years you will see the results of this research in the pre-clinical trial stages. That would be a goal for us.”

But the research goes on in the meantime. “There is a clear link between obesity and allergies and obesity is a big problem in Ireland at present,” he says.

“Obesity changes the immune system and the nuocyte cell we have discovered is associated with fat and we are researching that link at the moment.

“This is very important research as childhood obesity is a growing problem here and these are the adults of the future who will be more susceptible to asthma and other allergic conditions if something isn’t done about it.”