By Dr Joerg Mattes
Last year our paediatric and respiratory research team published a paper in the world’s leading journal for biomedical research, Nature Medicine, after detecting molecular signals generated very early in the disease process for virus-and allergen-induced asthma.
The discovery has moved us significantly closer to identifying the source of serious asthma attacks.
We spent several years tracking the new pathway and investigating the mechanisms that trigger airway inflammation, working in close collaboration with researchers from the Imperial College London and the University of Cincinnati.
The tri-nation study targeted the common cold (rhinovirus), which is the virus that causes most asthma attacks, along with the effects caused by allergens such as house dust mites. A comprehensive gene expression analysis led to the initial discovery of the signals – proteins known as midline 1 and protein phosphatase 2A.
These proteins are generated in the innermost layer of the airways, where the body has first contact with allergens and viruses, and once activated they appear to modulate many other disease factors. Obviously it is better to target these earlier signals rather than the hundreds of downstream effects.
The World Health Organisation estimates around 300 million people worldwide suffer from asthma and it represents a large unmet medical need as there is currently no cure. In Australia alone, asthma results in more than 30,000 hospitalisations per year, many of which are children, and we know that two-thirds of these asthma attacks are caused by viruses.
Asthmatics experience severe and prolonged symptoms when infected with the common cold virus or exposed to allergens, both of which promote inflammation in the lungs and production of mucus.
Asthma attacks are currently treated similarly, regardless of whether they are caused by viruses or allergens. However virus-induced effects are much less responsive to current therapies, which is why this investigation is so important.
The next phase is to test therapeutic strategies to modify the pathway, setting a platform for the development of targeted drugs ahead of full clinical trialling. Negotiations with international pharmaceutical companies are already underway.
The advantage of developing a small molecular inhibitor of Midline-1 is that it would be non-steroidal, therefore overcoming the increasing resistance to current steroid-based and other anti-inflammatory asthma treatments.
*** Professor Joerg Mattes is Chair – Paediatrics & Child Health at the University of Newcastle, and clinical Director of the Paediatric Lung Function Service at Kaleidoscope (John Hunter Children’s Hospital).