Don't hold your breath. A potential long-term treatment for asthma – the chronic and incurable condition in which your body occasionally forgets how to breathe – is showing promise, a new study in mice suggests. Unike current treatments, which mostly focus on curbing the immediate effects of asthma, this new approach, published in the journal Respiratory Medicine, targets the permanent damage caused by the disease – and while it might still be a way off testing in humans, for asthmatic mice at least, the results are encouraging. Approximately 25 million people in the US have asthma. To put that number in context, it means that for every group of 13 people in the country – that’s only around half a primary school class – one person will have the disease. So it’s no surprise that scientists have been searching for treatments for millennia. Granted, the earliest attempts don’t sound too enticing: an Egyptian papyrus from the mid-1550s BCE, for example, recommended burning highly toxic flowers over heated bricks and breathing the condensed fumes in through a straw, while Pliny the Elder listed among potential medicines such mouth-watering options as drinking the blood of wild horses, bear's gall mixed with water, or millipedes soaked in honey. It must have come as some relief when the metered dose inhaler, or MDI, was invented in the 1950s. From there, we got the wide range of therapeutic devices asthmatics know and use today – including inhalers, tablet medications, high-tech sensors, injected steroids, and more. But as major a leap forward as this is, there’s one thing all of the above have in common – or to be more accurate, don’t have in common. None of them address the structural changes in the airways and lungs caused by asthma – they can only treat the acute symptoms of the condition. Not so this new approach. “Asthma is characterized by the presence of airway remodeling, such as increased smooth muscle accumulation around the airways, collagen accumulation within the airway wall, excess mucus production and epithelial shedding as well as angiogenesis,” notes the paper. “These structural changes cause the airway wall to thicken and narrow; consequently, airflow is decreased, and lung function is impaired. This results in the characteristic symptoms seen in asthmatics, including episodes of wheezing and dyspnea,” the authors explain. And so they decided to focus on pericytes, a type of stem cell found in the lining of blood vessels. During an asthma attack, these cells move to the airway walls, where they go on to develop – as stem cells do – into muscle cells, or fibroblasts, or other cells that serve to make the airways thicker and less flexible. But what exactly makes the pericytes move like this? It’s thought to be related to a protein known as CXCL12 – a theory that was strengthened by the researchers’ observations that with “high levels of CXCL12 expression in the airways, pericytes were observed to uncouple from the airway microvasculature and demonstrated enhanced migration toward chemotactic stimuli.” So the key to a long-term asthma treatment, then, may be in blocking this protein – and that’s exactly what they did. The team introduced a brand new molecule called LIT-927 into the nasal passages of asthmatic mice, aiming to suppress the action of CXCL12 and therefore stop the wheezy little guys’ airways from thickening up. The experiment was a success: Mice who received the new molecule had a reduction in asthma symptoms within a week. Within two weeks, the condition had virtually disappeared. Even better: their airways showed much less evidence of asthma-induced injury, with walls that were thinner than the control group and more like those of healthy mice. “By targeting the changes in the airway directly, we hope this approach could eventually offer a more permanent and effective treatment than those already available, particularly for severe asthmatics who don’t respond to steroids,” Dr Jill Johnson, a Senior Lecturer at the University of Aston School of Biosciences and lead author of the study, said in a statement. So is it good news for asthmatics? Not yet, Johnson said: “Our work is still at an early stage, and further research is needed before we can begin to test this in people,” she cautioned. Given time, and funding, the team hope to investigate in greater detail the best dosage, time scales, and effects of this novel treatment. Even if all goes well, human trials would likely not start for several years. So until then, we suppose, it’s good news for asthmatic mice – but if you’re a human, don’t give up your inhaler just yet. Source
