Novel Asthma Gene Discovery
- Friday, August 21, 2009, 13:49
- Asthma
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- Erin:
- What is the discovery of this asthma gene, and why is it so important?
- Dr. Holgate:
- There are two answers to your question. The first relates to the fact that asthma is an inherited disorder, but inheritance alone is insufficient to account for the disease. Inheritance does make one person more susceptible to developing the disease when compared to another. And what we’ve discovered with our collaborators in the United States is a novel gene that makes a novel protein that appears to be linked to the susceptibility of this disease and, as you said, accounts for up to 40 percent of its clinical expression. “What we’ve discovered is a novel gene that appears to account for up to 40 percent of asthma’s clinical expression.”
The second aspect of this research is what the gene means to patients. If we are able to identify, as we have done in this particular case, a novel protein that’s linked to the initiation of asthma in families who develop the disease, then we could develop new drugs to target this protein and produce an entirely new way of preventing and treating the disease.
- Erin:
- So a lot of hope comes out of this discovery.
- Dr. Holgate:
- Indeed it does, and in my experience of 25 years in asthma research, this to me is the greatest discovery that’s been made, and you can imagine how thrilled we all are about that.
- Erin:
- Yes, I can. What do researchers now know about the genetic causes of asthma? What does this discovery mean in terms of that?
- Dr. Holgate:
- Asthma is a disease where both genes and environment are important, and there are going to be multiple genes involved in asthma. Indeed, many of these have already been described, but each one of the genes so far described only accounts for a tiny amount of the clinical expression of asthma, and what we found here, quite by surprise in some respects, is a gene that accounts for a much larger amount of the clinical expression. And it’s because of that finding that we’re really so thrilled about it.
- Erin:
- Does this change the way we look at the disease?
- Dr. Holgate:
- It certainly does. Previously, we felt that environment was the key factor in driving asthma, and many people in the asthma community know that allergen exposure, cigarette smoke exposure, virus infections, and even diet have been linked to the development of asthma, especially during early childhood. What this new discovery tells us is that if there’s a genetic abnormality running in parallel, then the risk of these children developing asthma is increased by 100,000 to one. So, basically it tells us that we’ve got a major – major – key to the understanding of this disease mechanism.
- Erin:
- Is this gene passed along to any particular ethnic groups?
- Dr. Holgate:
- That’s a good question, and I can’t clearly answer it at this stage. I should add that our collaborators, GTC [Genome Therapeutics Corporation] and Schering-Plough in the United States, collected, in addition to the English families that we collected here, 110 U.S. families to study. These were of different ethnic backgrounds, and as I understand it, the gene that we found in the European families has also now been found in these American families, as well. This is why we’re so convinced that this new gene is a major gene: because it’s crossed various cultural and national barriers. “This is why we’re so convinced that this new gene is a major gene: because it’s crossed various cultural and national barriers.”
- Erin:
- Since our DNA closely resembles each other’s, the asthma gene is present in many of us, it seems.
- Dr. Holgate:
- It would seem that’s the case, and I suppose one might predict that, especially if a single gene is predicting 40 percent of the clinical expression of the disease.
- Erin:
- Is this the first asthma gene that has been discovered?
- Dr. Holgate:
- This is not the first asthma gene. Probably 20 or 25 mutations have been described in various known asthma genes. But this is the first entirely “novel” gene – in other words, it was never suspected before. And it’s the first gene to have such a powerful effect on the clinical expression of the disease.
- Erin:
- And because it has such a powerful effect on clinical expression, does this mean that there will be new kinds of treatments developed?
- Dr. Holgate:
- Of course, the whole idea of discovering new genes is to find out why they lead to the development of asthma; and then, by targeting the particular proteins the gene makes, to interfere with this and stop asthma from either developing or progressing. And this, indeed, is what we hope will happen. In many ways, what makes this tripartite relationship so intriguing is that we have an academic group in the U.K. liaising with a drug company and a gene discovery company in the United States, and all three of our groups are needed now to move this forward to its next stage. The genome company is needed to find out what the gene does and how it’s going to operate, the pharmaceutical company is needed to develop the new drugs targeting this particular gene, and our work here in the U.K. is targeted to which particular asthmatic components might reflect the gene’s activity at different stages during the disease evolution.
- Erin:
- The whole field of genetic research is going to create a new series of collaborations, is it not?
- Dr. Holgate:
- Indeed it is, because this is expensive research, and it requires skills of differing types. And no single group on its own, really, can make these discoveries. We need partnerships like this, and that’s why we’re especially thrilled that this has worked out so well.
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