Virus induced lung injury-investigation of mechanism of action of how modification of the enzyme OGG1 prevents development of pulmonary fibrosis

There are evidences for the role of virus infections in development of acute lung injury and pulmonary fibrosis.

Most recent example is Covid19 where a part of patients progress to severe lung inflammation due to dysregulated immune responses, followed by development of pumonary fibrosis.

Hence, there is a large unmet medical need for a new drug that combine antiinflammatory and antifibrotic therapeutic effects for these patients.

The enzyme OGG1 plays an important role in these conditions, it binds to its substrate 8-oxo guanine in genomic DNA and induce epigenetic modifications, resulting in upregulation of immune responses.

Modulating the activity of the enzyme has shown to efficently protect from inflammation and fibrosis in experimental lung disease models.The overall goal of this project is to understand the mechanism of action of a potential therapeutic drug based on OGG1 inhibition.

It is currently entering preclinical phase, and will be evaluated for treatment of severe lung injury and fibrosis associated with viral infections.In collaboration with Investigaciones Cientificas (CSIC) and Oslo universitet we will combine transcription studies, with genomic analysis of the changes produced at the chromatin level and epigenetic oxidative lesions.

The study will result in a map of altered genomic regions that could be correlated with changes in transcription. This would allow us to better understand how OGG1 inhibitors work in the pulmonary fibrosis disease models.