Idiopathic pulmonary fibrosis

What is idiopathic pulmonary fibrosis?

Idiopathic pulmonary fibrosis (IPF) is an incurable disease of unknown cause, which results in extensive scarring / fibrosis of the lungs.  Lung damage is often advanced when first diagnosed and invariably progresses to respiratory failure with only 20-30% of patients surviving 5 years from diagnosis [1].  IPF is a clinical target of high unmet medical need with existing treatments having limited effects on disease progression or survival rates.

The data

Studies conducted in preclinical rodent models of IPF have demonstrated efficacy of Cymerus MSCs, based on statistically significant improvements in multiple clinically relevant outcome measures, including levels of fibrosis, inflammation, dynamic lung compliance and airway resistance. announce the completion of a pre-clinical study that has provided further evidence in support of the highly potent anti-inflammatory effects of Cynata’s proprietary Cymerus MSCs. 

The studies were conducted by Professor Chrishan Samuel (a Monash Biomedicine Discovery Fellow and Head of the Fibrosis Laboratory, Department of Pharmacology at Monash University) in mice subjected to bleomycin (BLM)-induced pulmonary fibrosis, which mimics features of IPF in humans. The studies involved Cymerus MSC dosing either once or once-weekly over a 2-week treatment period and comparison with saline controls.

The key findings were as follows:

• Control animals suffered a 40% loss of dynamic lung compliance after bleomycin administration, as expected in this model. 
• However, when Cymerus MSC treatment was administered in a single dose 3 weeks later, or as a double dose at 3 and 4 weeks later, the loss of dynamic lung compliance was just 15%.
• Similarly, while bleomycin administration led to profound increase in interstitial inflammation and fibrosis, as well as increases in airway resistance, epithelial thickness and subepithelial ECM thickness, Cymerus MSC treatment dramatically reduced each of these harmful effects.

Additionally Cymerus MSCs:

• Significantly ameliorated the BLM-induced M2 macrophage, dendritic cell and T cell influx into the airways/lungs as well as pro-inflammatory TNF-α, IL-6 and IL-1β levels within the airways/lung;
• Significantly promoted anti-inflammatory IL-10 and IFN-γ levels within the airways/lung;
• Significantly reduced the BLM-induced pSmad2 levels and restored the BLM-induced loss of Smad7 levels within the airways/lung (without affecting pSmad3 levels);
• Did not affect MAP kinase levels nor CTGF, PDGF or ET-1 levels within the airway/lungs;
• Significantly restored or promoted the BLM-induced loss of MMP-13 and MMP-2 levels as well as the MMP-13/TIMP-1 and MMP-2/TIMP-2 balance (without affecting MMP-9 levels or the MMP-9/TIMP-1 balance); and
• Significantly reduced the BLM-induced interstitial collagen area, interstitial collagen area to tissue area ratio, interstitial collagen fibre density, thickness and length (without affecting interstitial collagen fibre cross-linking).
  

[1] Ley B, et al. Am J Respir Crit Care Med. 2011;183(4):431-40