Exploring the molecular landscape of COPD on single cell level
Within this research collaboration they will join forces with the biomarker discovery team of Genentech. These partners have a strong mutual interest in exploring the molecular disease drivers of COPD to discover new disease markers and potential new treatment options for this destructive chronic lung disease.
COPD is a devastating, invalidating, lung disease with no treatment modifying the disease course. COPD is currently the third leading cause of death worldwide causing 3.23 million deaths in 2019. Importantly, COPD represents the respiratory condition with the highest financial burden with a total annual cost in Europe of €141.4 billion, including €48.4 billion for healthcare and lost productivity costs and €93 billion in monetised value of disability-adjusted life-years (DALYs) lost.
Next to smoking cessation, current treatment strategies of COPD aim to improve symptoms and prevent exacerbations, yet there is no disease modifying treatment. The biggest drawback of today’s COPD treatment regime is that it is mainly based on disease severity and symptoms but not reflecting the individual’s disease pathology. To halt the worrying increase in the burden of COPD, disease management needs to be advanced with a focus on personalised treatment, for which more insight in heterogeneity of the disease drivers on the molecular level is needed.
This project aims to identify the molecular, epigenetic and cellular changes underlying disease pathology of mild and severe COPD, and also assess the impact of the smoking status of the patient. To establish this they will perform single nuclear RNA and ATAC sequencing analysis on lung tissue samples derived from patients with mild/moderate and severe COPD in comparison to clinically well-characterised subjects with normal lung function. The main outcome of this project will be cell type specific gene expression profiles (and information on chromatin accessibility) for mild/moderate and severe COPD that can be translated to novel disease and patient specific disease markers based on the extensive clinical phenotyping of the patients. In addition, they will assess the impact of smoking status on these molecular profiles, which will help them to understand and identify specific targets that they need to address, irrespective of smoking cessation, which should be the first line of treatment in patients with COPD.
