Development of recombinant surfactant protein D therapy to prevent neonatal chronic lung disease

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Premature infants have immature lungs which lack lung surfactant which is normally produced by the lungs and is essential for normal breathing. Premature infants therefore frequently require additional help to breathe after birth and are reliant on artificial respiratory support with ventilators and positive pressure devices in neonatal intensive care to keep their lungs from collapsing. Currently, babies born early receive surfactant replacement therapy which is derived from the lungs of animals. This has been very successful in saving their lives by stabilising their lungs and improving their ability to breathe. However current surfactant therapies in clinical use do not contain all of the components of normal human surfactant and more than half of babies now surviving after birth at less than 28 weeks gestation go on to develop chronic lung inflammation and neonatal chronic lung disease (nCLD), which leaves infants oxygen dependent and highly susceptible to life threatening reactions to common childhood viral infections, asthma and other chronic lung problems in later life. A component of the natural surfactant that is missing in current surfactant therapy is surfactant protein D (SP-D), a natural lung defence protein which plays an important role in keeping the lungs healthy and free from infection and inflammation. In fact, SP-D is so important in controlling lung inflammation that mice lacking the gene for SP-D spontaneously develop chronic lung inflammation causing emphysema, a destruction of the lung tissue that is common in smokers and in preterm babies whose lungs are immature and damaged by the need for positive pressure ventilation. SP-D has been shown to reduce inflammation in the lungs of preterm lambs. We have been able to produce a functional fragment of SP-D (rfhSP-D), have fully characterised its structure and shown that it works to reduce inflammation in animal models of human disease. Not only does treatment with rfhSP-D correct the emphysema in mice lacking SP-D, but the rfhSP-D is also effective in reducing inflammation in models of infection with bacteria, viruses, fungi and parasites as well as lung inflammation triggered by common fungal and house dust mite allergens. We aim to develop this fragment of the natural human surfactant protein as a new therapy to supplement surfactant treatments currently given to preterm babies, to see if this can help reduce the high incidence of chronic lung disease after preterm birth. To do this, we must first scale up production of the rfhSP-D to the required safety standards for human treatment and then carry out a clinical trial to see if babies can be treated safely with this additional missing surfactant protein. If this natural protein is shown to be safe and deliverable to the lungs of premature babies like current surfactant therapy, this will help determine the appropriate dosing regime for the next stage of clinical testing to see if supplementing current surfactant treatment with this extra protein will help reduce the incidence of chronic lung problems in babies born too early.