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RTD Success Stories - A breath of fresh air for young asthma sufferers

Asthma is an increasing chronic health issue in Europe, affecting the quality of life of millions and placing an unbearable strain on national health systems. Understanding how this respiratory disease may be caused could lead to new innovative treatments. An EU-funded study has uncovered strong evidence that a specific gene is involved in the development of asthma in children.

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The findings of the Asthma AND Ormdl3 project could change our understanding of childhood asthma, a potentially fatal condition which affects over 30 million children and adults in Europe. Michaela Schedel, project coordinator and researcher of the Asthma AND Ormdl3 project, focused on a specific gene called Ormdl3, which is found on one of the chromosomes, the chains of DNA in the cell nucleus, which encode genetic information. Previous studies suggested that Ormdl3 could play a role, but evidence was inconclusive. "Now, more than ever, we find ourselves in need of identifying insights into the function of novel asthma-related genes," says Dr Schedel. "Due to the complexity of the disease, many of the underlying mechanisms are still not well understood. Hence, with this project we aimed to increase our understanding of the biological function of Ormdl3, as insight on the role of this protein is limited and even less is known of its influence on asthma development." Understanding the causes of asthma Asthma is the most common chronic inflammatory disease of the airways, and its prevalence has drastically increased over the last few decades. Symptoms can range from mild to life-threatening, and although European children and adults have access to improved therapeutic strategies, fatal asthma attacks still occur. "Considering these aspects, it is indisputable that asthma is one of the leading health problems of our modern society," says Dr Schedel. Genetic susceptibility and environmental factors have long been thought to cause the development of asthma. However, scientific progress has often been slow due to the limitations of different experimental approaches, something which this project has addressed. The project used different experimental approaches in humans, and models of experimental asthma in mice. "These provided evidence that Ormdl3 may play a functional role in causing asthma and is potentially relevant in immune regulation early in life," explains Michaela Schedel. "Intriguingly, we were able to identify a number of novel Ormdl3 protein interaction partners likely to be involved in immunologically relevant pathways that regulate asthma." Ready for the next challenge Dr Schedel passionately believes that health professionals must be supported in being able to intervene and potentially prevent this condition. A better understanding of how asthma might develop is a critical breakthrough, but the success of this project now brings with it new challenges. As with many gene-disease susceptibility findings, there is often a bottleneck in moving on to the next step – namely, establishing gene-to-function relationships. Dr Schedel says that the relationship between the functional properties of Ormdl3 and the activation of immune-regulatory cells remains largely unknown. However, she is confident that the dual approach of analysing Ormdl3 function and regulation in both human systems and mice will help to advance our current understanding of causes and mechanisms in a respiratory disease such as asthma. This project was funded through the Marie Curie Actions, an EU research fund that gives researchers the possibility to gain experience abroad. It also encouraged a substantial transfer of knowledge, and helped to establish close ties with a leading respiratory centre in the US. In addition, the grant enabled Dr Schedel to establish herself as an independent researcher. The next steps, she says, are to determine how and to what extent these findings can be applied to the future development of novel preventive and therapeutic strategies. Only in this way can we advance our knowledge to substantially reduce the burden of this global health problem and improve the quality of life of asthmatics in Europe and around the world. - Project full name: Understanding of Ormdl3 biology will provide novel insight into the pathogenesis of asthma - Project acronym: Asthma AND Ormdl3 - Project reference number: 236137 - Asthma AND Ormdl3 Project Website - Name/country of project coordinator: Medizinische Hochschule Hannover, Germany - Total project cost: EUR 174 087 - EC contribution: EUR 174 087 - Project start/end: May 2009 to July 2011 - Other partner countries: Germany, United States