What is asthma?
Asthma is a chronic, long term lung condition that causes a person's airways to become inflamed, narrow and swell and produce extra mucus, which makes it difficult to breathe. Asthma is a debilitating condition that impacts over 330 million people globally and kills ~1,000 people every day .
Through a development collaboration with Monash University, Cynata has demonstrated that Cymerus™ MSCs are clearly effective in a well-established chronic allergic airways disease model in mice. The features of this model closely resemble the clinical manifestations of asthma in humans, so these results suggest that Cymerus MSCs may have potential as a treatment for asthma sufferers.
Cynata’s Cymerus MSCs were used in two preclinical studies; one that compared Cymerus MSCs to a control, and a second study that compared the effect of MSCs to corticosteroids (existing asthma treatment) and the effect as a combination therapy with corticosteroids.
The study using Cymerus MSCs alone, was published in the leading peer reviewed publication; FASEB Journal. The study demonstrated that Cymerus MSCs have significant beneficial effects on all three key components of asthma; airway inflammation, airway remodelling and airway hyperresponsiveness. IV administration of Cymerus MSCs partially but significantly reversed the experimentally induced increase in airway hyperresponsiveness while IN administration of Cymerus MSCs completely normalised airway hyperresponsiveness.
The second study reported that Cymerus MSCs showed a greater reduction airway hyperresponsiveness, airway remodelling and fibrosis compared to corticosteroid treatment and that combination therapy involving Cymerus MSCs and corticosteroids resulted in a pronounced synergistic effect, producing marked anti-inflammatory effects in addition to the benefits seen with Cymerus MSC treatment alone.
- Both intravenous (IV) and IN administration of Cymerus MSCs caused statistically significant improvements in the three main features of asthma: airway inflammation, airway remodelling and airway hyperresponsiveness (AHR).
- IV administration of Cymerus MSCs partially but significantly reversed the experimentally-induced increase in AHR (p<0.05 relative to untreated sensitised animals), while IN administration of Cymerus™ MSCs completely normalised AHR (p<0.001 relative to untreated animals with chronic allergic airways disease).
- IN delivery of Cymerus MSCs completely reversed pathologic collagen deposition in the lungs to levels seen in animals in which the asthma model was not induced. Pathologic collagen deposition is a sign of airway remodelling/fibrosis. Previous studies by the same group found that IN administration of other types of stem cells did not have similar effects, unless used in combination with other drugs.
- No adverse safety findings were observed.
- Daily administration of dexamethasone (a corticosteroid), demonstrated marked anti-inflammatory effects. It reduced airway inflammation by approximately 55% and airway inflammation induced goblet cell metaplasia (abnormal changes in the cells responsible for producing mucus) by approximately 80%. However, dexamethasone displayed weak anti-remodelling and anti-fibrotic effects, and only reduced airway hyperresponsiveness by approximately 30% over the 2 week-treatment period.
- In comparison, once-weekly administration of one million Cymerus MSCs resulted in striking reductions of airway remodelling, fibrosis and airway hyperresponsiveness. Most notably, subepithelial collagen deposition (a measure of fibrosis) and airway TGF-β1 expression levels (a measure of airway remodelling) were normalised to levels equivalent to mice in which asthma had not been induced, while airway hyperresponsiveness was reduced by 70-75%.
- When the two treatments were combined, a pronounced synergistic effect was achieved, resulting in similar anti-inflammatory effects to dexamethasone alone and similar reductions in remodelling, fibrosis and airway hyperresponsiveness to Cymerus MSCs alone.