Le site de vulgarisation scientifique de l’Université de Liège. ULg, Université de Liège

A gene named Adam
1/23/13

A protective effect

These results (2) thus clearly demonstrated, without any possible doubt, that the ADAMTS-12 protease plays a role in the expression of the asthma pathogenesis. A manifestly protective role because, when ADAMTS-12 is deficient, the asthmatic manifestations both in vivo and in vitro are more marked. 'To our knowledge, this is the first study which has shown that ADAMTS-12 has a role in an experimental asthma model' stresses Didier Cataldo. 'Because we have been able to show that deficiency in this enzyme provokes an increase in bronchial reactiveness and an increase in inflammation, we can conclude that ADAMTS-12 certainly has a protective effect, and it would be interesting to investigate the mechanism behind this. This is currently underway. '

'Our study is also interesting from a more general perspective,' he continues, 'because a few years ago, some research hypotheses had recommended investigation of protease inhibition, notably in slowing down the progress of cancer. The pharmaceutical industry therefore stepped into the breach, thinking they had discovered the goose that lays the golden egg, but without having a real understanding of this area. A multitude of unspecific metalloprotease inhibitors were thus developed ... and none of them resulted in anything. On the contrary, a number of clinical trials were interrupted, leading to millions and millions of dollars being lost. Why? Because nobody knew exactly about the biology of this family of enzymes. Once again, this demonstrates the usefulness of fundamental research! A lack of understanding of the range of protease families and cytokines with which we are working leads to unexpected and unknown interactions. Even if a beneficial result emerges, this may potentially be swamped by side effects due to lack of specificity of the approach. '

puffIt is thus understandable that when he is asked if this discovery is likely to have implications for the future treatment of asthma, the researcher remains cautious: 'Not yet! ' But these findings are nonetheless indispensable for the development of new therapeutic classes precisely because of the understanding of the network of molecular and cellular interactions remains paramount. 'For the time being', continues Didier Cataldo, provocatively, 'we treat asthma with corticosteroids. How do they act? We don't really know actually! The inhibit inflammation, but in doing so, they act on the expression of a very high number of different genes. We can't therefore say that we 'understand' what is going on. On a mechanistic point of view, we are still at the same stage as when we used suprarenal extracts in the 19th century in our therapeutic agents. Production methods may be more sophisticated, and administration through inhalation reduces the toxicity of the drugs, but we still don't know exactly what we are doing! We may find new therapeutic targets, including the mechanisms at work. '

Didier Cataldo's team are now trying understanding what the ADAMTS-12 protease interacts with on the molecular level. 'We have changed the level of research: we moved from the in vivo stage back to the purely molecular level. This means that this will take time, because these studies are highly complex. It's unlikely you'll hear any more about this molecule for a long time', he smiles. Research is often a waiting game ...

'To conclude' continues Professeur Cataldo, 'we can say that asthma is a polygenic disease for which a whole series of genes have been identified, and the links between cause and effect are more or less complex. Our contribution is to have proven that one of these genes is effectively linked to asthma because when we suppress it, asthma is aggravated. There is still a very long way to go before we will understand all genes associated with asthma and how they function, but our little contribution is ADAMTS-12. '

(2) Control of Allergen-Induced Inflammation and Hyperresponsiveness by the Metalloproteinase ADAMTS-12. Geneviève Paulissen, Mehdi El Hour, Natacha Rocks, Maud M. Guéders, Fabrice Bureau, Jean-Michel Foidart, Carlos Lopez-Otin, Agnès Noel, and Didier Cataldo. J Immunol published online 7 September 2012 ol.1103739
http://www.jimmunol.org/content/early/2012/09/07/jimmun

Page : previous 1 2 3

 


© 2007 ULi�ge