According to a preclinical asthma trial, an investigational stem cell platform technology called Cymerus MSC in conjunction with a daily corticosteroid had positive therapeutic effects on asthma symptoms.
Results found that once-weekly administration of one million Cymerus MSCs (mesenchymal stem cells) resulted in “striking reductions of airway remodelling, fibrosis and airway hyperresponsiveness” compared to corticosteroid dexamethasone, according to Cynata Therapeutics Ltd.
Cymerus utilizes induced pluripotent stem cells (iPSCs) to produce a particular type of MSC precursor, called a mesenchymoangioblast (MCA). The Cymerus platform provides a source of MSCs that is independent of donor limitations and provides an “off-the-shelf” stem cell platform for therapeutic product use, with a pharmaceutical product business model and economies of scale.
The study was conducted using a well-established mouse model of chronic allergic airways disease, which closely resembles asthma in humans, and includes several key features: airway inflammation; airway remodeling/fibrosis (structural changes in the airways due to excess fibrous tissue); and airway hyperresponsiveness, according to Cynata.
In the study, daily administration of dexamethasone demonstrated marked anti-inflammatory effects in this model. 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% (both p<0.001 vs untreated mice). 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 remodeling, fibrosis and airway hyperresponsiveness. Most notably, subepithelial collagen deposition (a measure of fibrosis) and airway TGF-?1 expression levels (a measure of airway remodeling) were normalized to levels equivalent to mice in which asthma had not been induced, while airway hyperresponsiveness was reduced by 70-75% (all p<0.001 vs untreated mice).
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 remodeling, fibrosis and airway hyperresponsiveness to Cymerus MSCs alone.
“The combination of Cymerus MSCs and dexamethasone resulted in maximal improvement for each endpoint measured. Hence, it can be concluded that such a combination therapy has the potential to improve treatment outcomes in asthmatic patients,” said associate professor Chrishan Samuel of the Monash Lung Biology Network.