Gene therapy for airway disease

Current Projects, Gene Therapy, Quality of Life Change
About This Project

Combined respiratory epithelial cell and gene therapy for amelioration of respiratory symptoms in children with Junctional Epidermolysis Bullosa

Lay summary

Epidermolysis Bullosa (EB) is a genetic disorder where patients suffer from extremely fragile surface tissues which painfully blister and scar with minimal trauma. It predominantly affects the external skin but the voice box and windpipe is significantly affected in some patients.

Treatment options for airway EB are very limited and often affected individuals will have difficulty in swallowing and gradually worsening breathing difficulties from airway scarring – eventual airway blockage creates the need for a tracheostomy (surgery where a small opening is made into the windpipe and a plastic tube is placed to allow airflow in and out).

Skin and airway lining research over the last two decades have identified many parallels; recent encouraging clinical case outcomes using gene-corrected skin grafts have therefore highlighted the possibility of delivering gene-corrected airway cells to cure airway disease. The work here aims to deliver laboratory-based tools to model EB airway disease, as well as to use lentiviral gene editing tools to correct EB-affected airway lining.

Scientific Summary

The effects of Epidermolysis Bullosa (EB) in the airway are heterogenous and the full extent of airway involvement remains unknown. In patients that suffer significant morbidity and mortality as a result of epithelial disease in the larynx and trachea, the most common mutation is in the LAMA3 gene, encoding the alpha3 chain of the laminin protein. Leveraging advances in the ability to expand airway epithelial stem/progenitor cells, this proposal aims to better characterise the airway epithelium from patients with airway EB and to develop autologous LAMA3 gene-edited airway epithelial cells as a potential curative approach.