Combined stem cell and drug therapy holds potential cure for asthma

Associate Professor Chrishan Samuel

Asthma treatment has barely changed over 20 years, with those who cannot easily control their condition relying on inhalers or using steroids which carry a high risk of weight gain, diabetes, osteoporosis and high blood pressure.

The main issue of asthma is that repeated attacks mean repeated cycles of injury to the airways with long term, irreversible loss of lung function. Current therapies treat the symptoms, they don’t address the problem. In short, there is no effective cure for asthma.

Monash researchers have found that a combination of drug therapy with stem cell transplants led to a complete reversal of lung damage in an animal model of asthma, opening the way to a potential cure for the disease, which affects one in ten Australians.

Associate Professor Chrishan Samuel, from the Monash Biomedicine Discovery Institute, and his team have published a report in the journal, Clinical Science, showing that the use of human amniotic stem cells led to a reduction in lung wall thickness, which contributes to the difficulty in breathing associated with asthma.

Importantly this stem cell therapy – when combined with the use of a drug called serelaxin – the combination therapy led to a complete reversal of the fibrosis (scar tissue accumulation) and adverse airway reactivity associated with chronic allergic airways disease to that of control animals.

Seralaxin is currently used in the treatment of acute heart failure and assists in widening the blood vessels while also having anti-fibrotic properties. According to Associate Professor Samuel, the drug is able to reduce the scarring associated with the damaged lungs, enabling improved viability and therapeutic efficacy of introduced stem cells.

Serelaxin (RLX030) is an investigational drug for the treatment of acute heart failure (AHF), targeting the relaxin receptor, Relaxin Family Peptide Receptor 1 (RXFP1). Serelaxin (recombinant human relaxin-2) has a number of organ protective properties and promotes vasodilation (widening of blood vessels) by increasing the production of nitric oxide (NO), a potent vasodilator while reducing fibrosis by inhibiting the pro-fibrotic actions of transforming growth factor (TGF)-b1 on collagen deposition.

The research team, which also included researchers from the Department of Anatomy and Developmental Biology (Prof. Sharon Ricardo) and Ritchie Centre (Dr. Rebecca Lim) at Monash University, also looked at the impact of mesenchymal stem cells which are naturally occurring precursors of muscle, fat, bone and tendon tissues.  They found that these cells, when combined with Seralaxin, also led to a normalizing of the lung tissue in animals with asthma. The importance of this is that mesenchymal stem cells do not trigger an immune reaction in recipients even when they come from an unrelated donor, leading to the use of a drug/stem cell combination as a potential cure for asthma.

According to Associate Professor Samuel, these combination therapies may offer a novel means to treat asthma, “particularly in patients who are resistant to corticosteroid therapy.”