Scientists at the University of Southampton have
discovered a potential and novel way of preventing
asthma at the origin of the disease, a finding that
could challenge the current understanding of the
condition.
The research, published in the Journal of Clinical
Investigation Insight, analysed the impact of the
gene ADAM33, which is associated with the
development of asthma.
ADAM33 makes an enzyme, which is attached to cells
in the airway muscles.
When the enzyme loses its anchor to the cell
surface, it is prone to going rogue around the lung
causing poorer lung function in people who have
asthma.
The studies in human tissue samples and mice, led by
Hans Michel Haitchi, an MRC Clinical Scientist
Fellow and Associate Professor in Respiratory
Medicine at the University of Southampton, suggests
that if you switch off ADAM33 or prevent it from
going rouge, the features of asthma - airway
remodelling (more muscle and blood vessels around
the airways), twitchiness and inflammation - will be
reduced.
“This finding radically alters our understanding of
the field, to say the least,” says Professor Haitchi.
“For years we have thought that airway remodelling
is the result of the inflammation caused by an
allergic reaction, but our research tells us
otherwise.”
The first study showed that rogue human ADAM33
causes airway remodelling resulting in more muscle
and blood vessels around the airways of developing
lungs but it did not cause inflammation. When a
house dust mite allergen was introduced, which is a
common human allergen, both, airway remodelling and
allergic airway inflammation were more significantly
enhanced.
In another study, remodelling of the airway was
shown in mice that had ADAM33 switched on from in
utero. The gene was then switched off and the airway
remodelling was completely reversed.
Furthermore they studied the impact of house dust
mite allergen on asthma features in mice that had
the ADAM33 gene removed. Airway remodelling and
twitchiness as well as airway inflammation rates
were significantly reduced by 50 per cent and
respectively 35 per cent in mice that did not have
the rogue gene.
These findings identify ADAM33 as a novel target for
disease modifying therapy in asthma.
Professor Haitchi said: “Our studies have challenged
the common paradigm that airway remodelling in
asthma is a consequence of inflammation. Instead, we
have shown that rogue human ADAM33 initiates airway
remodelling that promotes allergic inflammation and
twitchiness of the airways in the presence of
allergen.”
“More importantly, we believe that if you block
ADAM33 from going rogue or you stop its activity if
it does go rogue, asthma could be prevented. ADAM33
initiated airway remodelling reduces the ability of
the lungs to function normally, which is not
prevented by current anti-inflammatory steroid
therapy. Therefore, stopping this ADAM33 induced
process would prevent a harmful effect that promotes
the development of allergic asthma for many of the
5.4 million people in the UK with the condition.”
About ADAM33 - updated on 16-Jul-2016
NCBI - National Center for Biotechnology Information
ADAM33 ADAM metallopeptidase domain 33 [ Homo
sapiens (human) ]
Link...
For more information
Journal of Clinical Investigation Insight
Soluble ADAM33 initiates airway remodeling to
promote susceptibility for allergic asthma in early
life
Link...
Medical Research Council MRC
Link...
MDN |