Developing a new gene therapy for babies born with a rare severe lung condition

Lung surfactant deficiency is a rare condition that causes breathing problems. Babies with a severe form of the disease caused by faults in the ABCA3 gene will struggle to breathe after birth. Sadly, their treatment options are limited – and without a lung transplant, less than one in five children will live to celebrate their fifth birthday. [1] Professor Deborah Gill of the University of Oxford is carrying out laboratory research that could ultimately lead to a new treatment for newborn babies with this severe lung condition. She hopes this work will lead to a brighter future for children and their families affected by this devastating disease.

This project is jointly funded by Action Medical Research and LifeArc.

How are children’s lives affected now?

Lung surfactant is a complex mixture of fats and proteins that lines the lung tissue and makes breathing easy. Without normal surfactant, the lungs can collapse, leading to life-threatening breathing difficulties.

“Sometimes babies are born with very severe breathing difficulties that don’t respond to the usual treatments,” says Professor Gill. “They will need to be placed on a ventilator in intensive care – and sadly, their chances of survival are very poor.”

Research has identified faults in several genes that can cause lung surfactant deficiency – including ABCA3, which provides the instructions for making a protein involved in surfactant production. Faults in this gene can cause life-threatening breathing difficulties in newborn babies or milder symptoms in older children.

“Treatment options are limited for babies born with severe lung surfactant deficiency caused by faulty genes such as ABCA3,” says Professor Gill. “New life-saving therapies are desperately needed to provide hope for children and their families affected by this rare disease.”

How could this research help?

“Our goal is to develop a new gene therapy for babies with severe breathing problems caused by faults in the ABCA3 gene,” says Professor Gill.

The researchers plan to use a harmless virus to deliver a working copy of the ABCA3 gene into the baby’s lung cells. By enabling babies to make normal lung surfactant, this treatment should help them to breathe without mechanical ventilation.

“We will first carry out experiments to test the effectiveness of the approach in human cells and in a laboratory model of ABCA3-deficiency,” says Professor Gill. “Our results will indicate whether this gene therapy is likely to help babies with this rare and devastating condition.”

The next step would be to set up a clinical trial to test the safety and effectiveness of delivering the treatment directly into babies’ lungs through the ventilator breathing tube.

References

1. Kröner, C. et al. Lung disease caused by ABCA3 mutations. Thorax 2017; 72(3):213-220.

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