The resokine protein reduced interstitial lung disease (ILD) in mice, according to one of two presentations that aTyr Pharma will make at the American Thoracic Society International Conference in Washington, which starts today.
Atry derived its Resolaris therapy from resokine, which helps prevent the immune system from turning against healthy cells. Scientists refer to that process as maintaining immune tolerance.
Resolaris is derived from the naturally occurring resokine protein, also known as HARS, for histidine aminoacyl tRNA synthetase.
Both of ATyr’s presentations at the conference, which runs through May 24, will be poster sessions. One study makes a link between a shortage of resokine in the blood and the development of ILD. It is titled “The Resokine Pathway Is Implicated in the Pathology of Interstitial Lung Disease.”
People whose bodies produce Jo-1 antibodies often develop ILD, research has shown. ATyr researchers discovered that the antibodies reduce blood levels of resokine.
Using blood samples, the team noted that the antibodies appear to go after a resokine component called SV9 that is common in normal lung tissue.
To learn about resokine’s connection with lung disease, researchers triggered antibodies in mice. The loss of the protein led to T-cells and other immune cells infiltrating the mice’s lung tissue.
The team also discovered that immune cells traveled to muscle tissue, a finding supporting the notion that resokine is involved in inflammatory muscle diseases, too.
Another finding was that when researchers gave the mice bleomycin, an agent used to trigger fibrosis, those with certain gene mutations developed a more severe lung disease.
At one point, researchers exposed cells in a lab to inflammation-triggering molecules that are known to be involved in the early processes of lung inflammation and fibrosis. The result was an increase in the amount of resokine the cells secreted.
The key finding in the other presentation aTyr will make is that resokine can reduce lung disease in mice with interstitial lung disease that includes fibrosis. The presentation is titled “Resokine Modulates Immune Cell Infiltration into the Lung and Provides Therapeutic Activity in a Bleomycin-Induced Lung Fibrosis Model,”
To trigger fibrosis, the researchers put bleomycin in the mice’s windpipes. A week later the team gave the animals one of three resokine treatments. Some received Resolaris, aTyr’s man-made version of resokine; some an SV9 resokine fragment; and the others a fusion protein, or a coupling of the protein and part of an antibody.
Scans showed that resokine improved the mice’s lung disease as early as a week after administration, the team said. The presentation abstract did not say if the three treatment modes led to different levels of lung-disease improvement.
Two weeks after the treatment, lung tissue analysis revealed less fibrosis in the mice and reduced levels of immune and fibrotic factors in their bronchoalveolar washing fluid.
The results supported aTyr’s belief that resokine can be used to treat fibrotic and inflammatory ILDs, the researcher said.