Genetic studies of severe asthma to identify putative targets for drug development
Approved Research ID: 88144
Approval date: August 9th 2022
This project will try to discover genetic risk factors and biological pathways involved in severe asthma and could inform the development of new treatments.
Asthma is a common lung condition affecting children and adults, with several symptoms including breathlessness, wheezing and cough. Most patients control asthma thanks to existing treatments, but 3-10% of them suffer from severe asthma, a worse type that does not respond well to current medications, has a large impact on health and life quality, and is a burden on the healthcare system. Several large scale genetic studies, called genome-wide association studies or GWAS, have found associations with asthma, including severe type. However, the precise variants and genes causing increased risk of this worse condition are still unknown. My project aims at increasing our knowledge and informing the management of severe asthma in public health strategies. In doing so, this study will mainly look at three directions: 1) perform an updated genetic study of severe asthma to identify potentially causal variants and genes using individuals from the UK, with a possibility to expand this analysis to other world populations; 2) understand how these factors alter risk of asthma using human airway models in laboratory; 3) explore the potential of our findings for drug development during a placement at AstraZeneca.
This project has been designed in a timeline of four years: starting from a genetic study to find the associated variants with severe asthma (one and a half year), to validate and find the causal ones with the use of computational and laboratory experiments (one and a half year), down to interpretation of their biological role and their application in the drug development process (last year).
Public health impact:
It will contribute to discovering new variants associated with this worse condition and to identify the pathway affected by these variants and ultimately find the causal factor triggering the manifestation of a severe asthma phenotype. Combing this new knowledge, we hope to translate it into practical thanks to a drug development led by genetic insights. If successful, it will help to understand causal mechanisms of severe asthma and inform better treatments that patients could benefit from.